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Ivanov, Konstantin A., Volker Thiel, Jessika C. Dobbe, Yvonne van der Meer, Eric J. Snijder, and John Ziebuhr. "Multiple Enzymatic Activities Associated with Severe Acute Respiratory Syndrome Coronavirus Helicase." Journal of Virology 78, no. 11 (June 1, 2004): 5619–32. http://dx.doi.org/10.1128/jvi.78.11.5619-5632.2004.
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ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. Coronavirus replication and transcription are highly specialized processes of cytoplasmic RNA synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase, helicase, and protease activities, also involves a series of RNA-processing enzymes that are not found in most other RNA virus families. Here, we characterized the enzymatic activities of a recombinant form of the SARS-CoV helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N-terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex-unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5′-to-3′ direction and features a remarkable processivity, allowing efficient strand separation of extended regions of double-stranded RNA and DNA. Characterization of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities revealed that all natural nucleotides and deoxynucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than other nucleotides. Furthermore, we established an RNA 5′-triphosphatase activity for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5′ cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5′-triphosphatase activities of nsp13 have a common active site. Finally, we established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to membranes that appear to be derived from the endoplasmic reticulum and are the likely site of SARS-CoV RNA synthesis.
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A El-Masry, Eman. "Immunization against severe acute respiratory syndrome Coronavirus 2: an overview." African Health Sciences 21, no. 4 (December 14, 2021): 1574–83. http://dx.doi.org/10.4314/ahs.v21i4.11.
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In the past years, numerous new fatal infections have emerged, including Ebola, Nipah, and Zika viruses, as well as coronaviruses. Recently, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged in China, and were then transmitted all over the world, causing the coronavirus disease-19 (COVID-19) pandemic, which is transmitted at a higher rate than other diseases caused by coronaviruses. At the time of writing this review, COVID-19 is not contained in most countries in spite of quarantine, physical distancing, and enhanced hygiene measures. In this review, I address different methods for passive and active immunization against this virus, which is known to cause fatal respiratory disease, including natural passive immunization by breast milk, natural active immunization by herd immunization, artificial passive immunization by convalescent plasma or monoclonal antibodies, and artificial active immunization by vaccination. I hope this review will help design a prophylactic approach against outbreaks and pandemics of related coronaviruses in the future.
Keywords: Breastfeeding; COVID-19; herd immunity; monoclonal antibodies; SARS-CoV; vaccine.
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Zoghi, Sina, Hossein Jafari Khamirani, Seyed Alireza Dastgheib, Mehdi Dianatpour, and Alireza Ghaffarieh. "An analysis of inhibition of the severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase by zinc ion: an in silico approach." Future Virology 16, no. 5 (May 2021): 331–39. http://dx.doi.org/10.2217/fvl-2020-0369.
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Background: Coronavirus disease 2019 is caused by exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was reported that Zn2+ is an inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV). We hypothesize that the same applies to the newly discovered SARS-CoV-2. Material & methods: We compared the structure of RNA-dependent RNA polymerase between SARS-CoV and SARS-CoV-2. The RdRp’s binding to Zn2+ was studied by metal ion-binding site prediction and docking server. Results: Several regions containing key residues were detected. The functional aspartic acid residues RdRp, 618D, 760D and 761D were among the predicted Zn2+-binding residues. Conclusion: The most probable mechanism of inhibition of RdRp by Zn2+ is binding to the active aspartic acid triad while other binding sites can further destabilize the enzyme or interfere with the fidelity-check mechanism.
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Lamirande, Elaine W., Marta L. DeDiego, Anjeanette Roberts, Jadon P. Jackson, Enrique Alvarez, Tim Sheahan, Wun-Ju Shieh, et al. "A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters." Journal of Virology 82, no. 15 (May 7, 2008): 7721–24. http://dx.doi.org/10.1128/jvi.00304-08.
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ABSTRACT The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.
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Poutanen, Susan M., Mary Vearncombe, Allison J. McGeer, Michael Gardam, Grant Large, and Andrew E. Simor. "Nosocomial Acquisition of Methicillin-ResistantStaphylococcus aureusDuring an Outbreak of Severe Acute Respiratory Syndrome." Infection Control & Hospital Epidemiology 26, no. 2 (February 2005): 134–37. http://dx.doi.org/10.1086/502516.
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AbstractObjective:The four hospitals assessed in this study use active surveillance cultures for methicillin-resistantStaphylococcus aureus(MRSA) and contact precautions for MRSA-positive patients as part of routine infection control practices. The objective of this study was to determine whether nosocomial acquisition of MRSA decreased in these hospitals during an outbreak of severe acute respiratory syndrome (SARS) when barrier precautions were routinely used for all patients.Design:Retrospective cohort study.Setting:Three tertiary-care hospitals (a 1,100-bed hospital; a 500-bed hospital; and an 823-bed hospital) and a 430-bed community hospital, each located in Toronto, Ontario, Canada.Patients:All admitted patients were included.Results:The nosocomial rate of MRSA in all four hospitals combined during the SARS outbreak (3.7 per 10,000 patient-days) was not significantly different from that before (4.7 per 10,000 patient-days) or after (3.4 per 10,000 patient-days) the outbreak (P= .30 andP= .76, respectively). The nosocomial rate of MRSA after the outbreak was significantly lower than that before the outbreak (P= .003). Inappropriate reuse of gloves and gowns and failure to wash hands between patients on non-SARS wards were observed during the outbreak. Increased attention was paid to infection control education following the outbreak.Conclusions:Inappropriate reuse of gloves and gowns and failure to wash hands between patients may have contributed to transmission of MRSA during the SARS outbreak. Attention should be paid to training healthcare workers regarding the appropriate use of precautions as a means to protect themselves and patients.
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Mostafa, Ahmed, Ahmed Kandeil, Yaseen A. M. M. Elshaier, Omnia Kutkat, Yassmin Moatasim, Adel A. Rashad, Mahmoud Shehata, et al. "FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2." Pharmaceuticals 13, no. 12 (December 4, 2020): 443. http://dx.doi.org/10.3390/ph13120443.
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(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.
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Fylenko, B. M., V. I. Babenko, N. V. Royko, I. I. Starchenko, S. A. Proskurnya, and A. O. Byelyayeva. "Morphological Manifestations of COVID-19-Associated Pneumonia." Ukraïnsʹkij žurnal medicini, bìologìï ta sportu 7, no. 2 (May 6, 2022): 82–87. http://dx.doi.org/10.26693/jmbs07.02.082.
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The purpose of study was to study the pathomorphological changes of COVID-19-associated pneumonia in its severe course on the basis of autopsies with substantiation of pathogenetic links of clinical and morphological manifestations. Materials and methods. The study of changes of COVID-19-associated pneumonia in its severe course was performed on the basis of autopsies of 16 deceased individuals using macroscopic and microscopic methods. All patients had chronic diseases during their lifetime, which contributed to the severe course of COVID-19. Results and discussion. The severe course of COVID-19 is manifested by conventional morphological signs of acute respiratory distress syndrome and vascular wall lesions with the development of hypercoagulable syndrome. Autopsy revealed characteristic macroscopic changes in the lungs that distinguish this disease from other infectious diseases of the respiratory system. Microscopically, changes were observed in the lung tissue, which corresponded to the proliferative phase of diffuse alveolar damage, which is a morphological sign of clinical manifestations of acute respiratory distress syndrome. Deposits of homogeneous eosinophilic masses were found in the lumens of the alveoli, which unevenly covered the walls of the respiratory parts. Hyperplasia and metaplasia of type II alveolocytes was characteristic morphological feature of COVID-19-associated pneumonia. Sporadic altered hyperchromic pneumocytes were detected, often with the formation of symplasts associated with the cytopathic effect of SARS-CoV-2. The development of acute respiratory distress syndrome in COVID-19-associated pneumonia is based on the mechanism involved in the release of SARS-CoV2 from affected type II pneumocytes, leading to their destruction. As a result, specific inflammatory mediators are released, which stimulate macrophages that synthesize biologically active substances, increasing the permeability of capillaries and leading to the accumulation of exudate in the alveoli. Destruction of type II pneumocytes also reduces surfactant production, causing alveolar collapse, impaired gas exchange, and refractory hypoxemia. Pulmonary vascular endotheliitis with widespread thrombosis is also the prominent sign of acute respiratory distress syndrome in severe COVID-19-associated pneumonia. Conclusion. Pathomorphological studies indicate that the direct effect of SARS-CoV-2 on the epithelium of the respiratory tract and alveoli leads not only to its damage, but also trigger a cascade of reactions that cause the development of acute respiratory distress syndrome
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Isnaini, Nadia, Khairan Khairan, Meutia Faradhilla, Elly Sufriadi, Vicky Prajaputra, Binawati Ginting, Syaifullah Muhammad, and Raihan Dara Lufika. "A Study of Essential Oils from Patchouli (Pogostemon cablin Benth.) and Its Potential as an Antivirus Agent to Relieve Symptoms of COVID-19." Journal of Patchouli and Essential Oil Products 1, no. 2 (December 23, 2022): 27–35. http://dx.doi.org/10.24815/jpeop.v1i2.23763.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of virus that attacks the respiratory system and has caused the global epidemic of coronavirus disease 2019 (COVID-19). Some persons who are infected with this virus develop symptoms ranging from a typical cold to fever to more severe illnesses, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The development of a SARS-CoV-2 vaccine is being actively researched but will likely take more than a year to become available to the general public. As a result, numerous researchers are actively extracting the components of active chemicals in herbal plants with antiviral potentials, such as patchouli (Pogostemon cablin Benth.). Patchouli essential oil, found in this Lamiaceae plant, has a wide range of effects, including antibacterial, antifungal, antioxidant, antimutagenic, anticancer, anti-inflammatory, and aromatherapy. More than 140 chemicals have been isolated and identified from the patchouli plant, including terpenoids, phytosterols, flavonoids, organic acids, lignins, alkaloids, glycosides, alcohols, and aldehydes. Patchouli essential oil is mainly composed of sesquiterpene molecules, most of which are patchouli alcohol. Essential oils derived from herbal plant extracts have also been shown to be potent antiviral agents against various viruses. The efficacy of patchouli essential oil, as well as its potential as an antiviral agent to treat SARSCoV-2, will be investigated in this review.
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Rha, Brian, Joana Y. Lively, Janet A. Englund, Mary A. Staat, Geoffrey A. Weinberg, Rangaraj Selvarangan, Natasha B. Halasa, et al. "Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children: Multicenter Surveillance, United States, January–March 2020." Journal of the Pediatric Infectious Diseases Society 9, no. 5 (June 18, 2020): 609–12. http://dx.doi.org/10.1093/jpids/piaa075.
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Abstract Previous reports of coronavirus disease 2019 among children in the United States have been based on health jurisdiction reporting. We performed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing on children enrolled in active, prospective, multicenter surveillance during January–March 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2–positive cases were identified March 20–31 despite evidence of rising community circulation.
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Hashimi, Marziah, Thomas Sebrell, Jodi Hedges, Deann Teresa Snyder, Katrina Lyon, Michelle D. Cherne, Amanda Robison, et al. "Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in a Bat Gastrointestinal Organoid Model." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 125.34. http://dx.doi.org/10.4049/jimmunol.208.supp.125.34.
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Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is thought to have originated in bats, since multiple viruses with a high level of genetic similarity have been identified in bats. In addition to respiratory symptoms, COVID-19 frequently involves gastrointestinal symptoms such as diarrhea and vomiting, indicating the SARS-CoV-2 can target the gastrointestinal (GI) tract. However, there is no robust in vitro model for assessing the SARS-CoV-2 infection in the bat GI tract. Here, we established gastrointestinal organoid cultures from Jamaican fruit bats (JFB),( Artibeus jamaicensis), which replicated the characteristic morphology of the gastrointestinal epithelium and showed tissue specific gene expression patterns and cell differentiation. To analyze whether JFB intestinal epithelial cells are susceptible to SARS-CoV-2, we performed in vitro infection experiments. While increased SARS-CoV-2 RNA was detected in both cell lysates and supernatants from the infected organoids after 48 h, there was no evidence of active viral replication, and no infectious virus was produced. However, the JFB distal organoids significantly upregulated anti-viral and pro-inflammatory genes in response to SARS-CoV-2. Unexpectedly, SARS-CoV-2 infected JFB organoids had a decreased incidence of apoptotic cell death. Collectively, our data suggest that primary intestinal epithelial cells from JFBs are resistant to SARS-CoV-2 infection and cell damage, likely because they are able to mount a strong antiviral interferon response.
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Borbone, Nicola, Gennaro Piccialli, Giovanni Nicola Roviello, and Giorgia Oliviero. "Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses." Molecules 26, no. 4 (February 13, 2021): 986. http://dx.doi.org/10.3390/molecules26040986.
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Coronaviruses (CoVs) are positive-sense RNA enveloped viruses, members of the family Coronaviridae, that cause infections in a broad range of mammals including humans. Several CoV species lead to mild upper respiratory infections typically associated with common colds. However, three human CoV (HCoV) species: Severe Acute Respiratory Syndrome (SARS)-CoV-1, Middle East Respiratory Syndrome (MERS)-CoV, and SARS-CoV-2, are responsible for severe respiratory diseases at the origin of two recent epidemics (SARS and MERS), and of the current COronaVIrus Disease 19 (COVID-19), respectively. The easily transmissible SARS-CoV-2, emerging at the end of 2019 in China, spread rapidly worldwide, leading the World Health Organization (WHO) to declare COVID-19 a pandemic. While the world waits for mass vaccination, there is an urgent need for effective drugs as short-term weapons to combat the SARS-CoV-2 infection. In this context, the drug repurposing approach is a strategy able to guarantee positive results rapidly. In this regard, it is well known that several nucleoside-mimicking analogs and nucleoside precursors may inhibit the growth of viruses providing effective therapies for several viral diseases, including HCoV infections. Therefore, this review will focus on synthetic nucleosides and nucleoside precursors active against different HCoV species, paying great attention to SARS-CoV-2. This work covers progress made in anti-CoV therapy with nucleoside derivatives and provides insight into their main mechanisms of action.
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McGill, Andrew R., Roukiah Kahlil, Rinku Dutta, Ryan Green, Mark Howell, Subhra Mohapatra, and Shyam S. Mohapatra. "SARS–CoV-2 Immuno-Pathogenesis and Potential for Diverse Vaccines and Therapies: Opportunities and Challenges." Infectious Disease Reports 13, no. 1 (February 4, 2021): 102–25. http://dx.doi.org/10.3390/idr13010013.
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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process’s key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants.
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Yao, Lin, Peijun Tang, Hui Jiang, Binbin Gu, Ping Xu, Xiafang Wang, Xin Yu, Jianping Zhang, Yu Pang, and Meiying Wu. "Household Clusters of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Suzhou, China." BioMed Research International 2021 (October 16, 2021): 1–7. http://dx.doi.org/10.1155/2021/5565549.
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Objectives. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus causing substantial morbidity and mortality worldwide. We performed a cross-sectional investigation of SARS-CoV-2 clusters in Suzhou to determine the transmissibility of the virus among close contacts and to assess the demographic and clinical characteristics between index and secondary cases. Methods. We review the clustered patients with SARS-CoV-2 infections in Suzhou between 22 January and 29 February 2020. The demographic and clinical characteristics were compared between index and secondary cases. We calculated the basic reproduction number ( R 0 ) among close contacts with SLI model. Results. By 22 February, 87 patients with SARS-CoV-2 infection were reported, including 50 sporadic and 37 clustered cases, who were generated from 13 clusters. On admission, 5 (20.8%) out of 24 secondary cases were asymptomatic. The male ratio of index cases was significantly higher than that of secondary cases. Additionally, the index cases were more likely to have fever and increased CRP levels than the secondary cases. The R 0 values of clusters displayed a significantly declining trend over time for all clusters. The relative risk of infection in blood-related contacts of cases versus unrelated contacts was 1.60 for SARS-CoV-2 (95% CI: 0.42-2.95). Conclusions. In conclusion, SARS-CoV-2 has great person-to-person transmission capability among close contacts. The secondary cases are more prone to have mild symptoms than index cases. There is no increased RR of secondary infection in blood relatives versus unrelated contacts. The high rate of asymptomatic SARS-CoV-2 infections highlights the urgent need to enhance active case finding strategy for early detection of infectious patients.
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Kwaan, Hau C., and Paul F. Lindholm. "The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective." International Journal of Molecular Sciences 22, no. 3 (January 28, 2021): 1283. http://dx.doi.org/10.3390/ijms22031283.
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The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinically, patients with COVID-19 run a rapidly progressive course of an acute respiratory tract infection with fever, sore throat, cough, headache and fatigue, complicated by severe pneumonia often leading to acute respiratory distress syndrome (ARDS). The infection also involves other organs throughout the body. In all three viral illnesses, the fibrinolytic system plays an active role in each phase of the pathogenesis. During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells. Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) are closely linked to the RAAS. In lesions in the lung, kidney and other organs, the two plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA), along with their inhibitor, plasminogen activator 1 (PAI-1), are involved. The altered fibrinolytic balance enables the development of a hypercoagulable state. In this article, evidence for the central role of fibrinolysis is reviewed, and the possible drug targets at multiple sites in the fibrinolytic pathways are discussed.
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Parihar, Arpana, Tabassum Zafar, Rekha Khandia, Dipesh Singh Parihar, Rupali Dhote, Yogesh Mishra, and Raju Khan. "In silico Analysis for the Repurposing of Broad-spectrum Antiviral Drugs against Multiple Targets from SARS-CoV-2: A Molecular Docking and ADMET Approach." Archives of Proteomics and Bioinformatics 3, no. 1 (May 11, 2023): 3–14. http://dx.doi.org/10.33696/proteomics.3.012.
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Background: Amidst the second wave of COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led the world devastated, and resulted in the death of millions of people with its deadly virulence potential. In comparison to similar virus outbreaks, such as severe acute respiratory syndrome coronavirus(SARS CoV) and middle east respiratory syndrome coronavirus (MERS CoV), COVID-19 led to severe morbidity and mortality. Various therapeutic interventions to combat the SARS-CoV-2 infection are actively investigated, but still, there is no specific drug with high anti-viral efficacy against the SARS-CoV-2 virus has been reported yet. The present work is an effort to represent the promising therapeutic efficacy of 52 broad-spectrum anti-viral drugs as a potential lead molecule to suppress SARS-CoV-2 infection. These are the drugs that have shown potential efficacy against several viral infections earlier. The present article discusses the comparative analysis of the therapeutic efficacy of available broad-spectrum anti-viral drugs via assessment of receptor-ligand interaction using the molecular docking approach. Results: Based on the molecular docking indications, we predict the potential importance of various broad-spectrum antiviral drugs that can be repurposed for the treatment of SARS-CoV-2. Molecular docking revealed that Remedesivir, Imatinib, Herbacetin, Zanamivir, Ribavirin, Dasabuvir, Rhoifolin, Sofosbuvir, Cirsimaritin, and 2H-Cyclohepta[b]thiophene-3-carboxamide having strong interactions with respective targets. Conclusion: The present piece of work strongly recommends the anti-viral potential of Zanamivir for RdRp enzyme inhibition, Herbacetin against receptor binding domain of spike protein, and main protease target, Adefovir for ACE2, and Ribavirin for endoribonuclease active site. The current predictions will enhance the clinical development of potential therapeutic drugs to combat the pandemic significantly.
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Choy, Wai-Yan, Shu-Guang Lin, Paul Kay-Sheung Chan, John Siu-Lun Tam, Y. M. Dennis Lo, Ida Miu-Ting Chu, Sau-Na Tsai, et al. "Synthetic Peptide Studies on the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Glycoprotein: Perspective for SARS Vaccine Development." Clinical Chemistry 50, no. 6 (June 1, 2004): 1036–42. http://dx.doi.org/10.1373/clinchem.2003.029801.
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Abstract Background: The S (spike) protein of the etiologic coronavirus (CoV) agent of severe acute respiratory syndrome (SARS) plays a central role in mediating viral infection via receptor binding and membrane fusion between the virion and the host cell. We focused on using synthetic peptides for developing antibodies against SARS-CoV, which aimed to block viral invasion by eliciting an immune response specific to the native SARS-CoV S protein. Methods: Six peptide sequences corresponding to the surface regions of SARS-CoV S protein were designed and investigated by use of combined bioinformatics and structural analysis. These synthetic peptides were used to immunize both rabbits and monkeys. Antisera collected 1 week after the second immunization were analyzed by ELISA and tested for antibody specificity against SARS-CoV by immunofluorescent confocal microscopy. Results: Four of our six synthetic peptides (S2, S3, S5, and S6) elicited SARS-CoV-specific antibodies, of which S5 (residues 788–820) and S6 (residues 1002–1030) exhibited immunogenic responses similar to those found in a parallel investigation using truncated recombinant protein analogs of the SARS-CoV S protein. This suggested that our S5 and S6 peptides may represent two minimum biologically active sequences of the immunogenic regions of the SARS-CoV S protein. Conclusions: Synthetic peptides can elicit specific antibodies to SARS-CoV. The study provides insights for the future development of SARS vaccine via the synthetic-peptide-based approach.
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Ingallinella, P., E. Bianchi, M. Finotto, G. Cantoni, D. M. Eckert, V. M. Supekar, C. Bruckmann, A. Carfi, and A. Pessi. "Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus." Proceedings of the National Academy of Sciences 101, no. 23 (May 25, 2004): 8709–14. http://dx.doi.org/10.1073/pnas.0402753101.
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Neuman, Benjamin W., David A. Stein, Andrew D. Kroeker, Michael J. Churchill, Alice M. Kim, Peter Kuhn, Philip Dawson, et al. "Inhibition, Escape, and Attenuated Growth of Severe Acute Respiratory Syndrome Coronavirus Treated with Antisense Morpholino Oligomers." Journal of Virology 79, no. 15 (August 1, 2005): 9665–76. http://dx.doi.org/10.1128/jvi.79.15.9665-9676.2005.
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ABSTRACT The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) is a potent pathogen of humans and is capable of rapid global spread. Peptide-conjugated antisense morpholino oligomers (P-PMO) were designed to bind by base pairing to specific sequences in the SARS-CoV (Tor2 strain) genome. The P-PMO were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral RNA motifs and secondary structures. Several virus-targeted P-PMO and a random-sequence control P-PMO showed low inhibitory activity against SARS coronavirus. Certain other virus-targeted P-PMO reduced virus-induced cytopathology and cell-to-cell spread as a consequence of decreasing viral amplification. Active P-PMO were effective when administered at any time prior to peak viral synthesis and exerted sustained antiviral effects while present in culture medium. P-PMO showed low nonspecific inhibitory activity against translation of nontargeted RNA or growth of the arenavirus lymphocytic choriomeningitis virus. Two P-PMO targeting the viral transcription-regulatory sequence (TRS) region in the 5′ untranslated region were the most effective inhibitors tested. After several viral passages in the presence of a TRS-targeted P-PMO, partially drug-resistant SARS-CoV mutants arose which contained three contiguous base point mutations at the binding site of a TRS-targeted P-PMO. Those partially resistant viruses grew more slowly and formed smaller plaques than wild-type SARS-CoV. These results suggest PMO compounds have powerful therapeutic and investigative potential toward coronavirus infection.
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Schulze, Jessica, Christin Mache, Anita Balázs, Doris Frey, Daniela Niemeyer, Heidi Olze, Steffen Dommerich, et al. "Analysis of Severe Acute Respiratory Syndrome 2 Replication in Explant Cultures of the Human Upper Respiratory Tract Reveals Broad Tissue Tropism of Wild-Type and B.1.1.7 Variant Viruses." Journal of Infectious Diseases 224, no. 12 (October 15, 2021): 2020–24. http://dx.doi.org/10.1093/infdis/jiab523.
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Abstract Background The upper respiratory tract (URT) is the primary entry site for severe acute respiratory syndrome 2 (SARS-CoV-2) and other respiratory viruses, but its involvement in viral amplification and pathogenesis remains incompletely understood. Methods In this study, we investigated primary nasal epithelial cultures, as well as vital explanted tissues, to scrutinize the tropism of wild-type SARS-CoV-2 and the recently emerged B.1.1.7 variant. Results Our analyses revealed a widespread replication competence of SARS-CoV-2 in polarized nasal epithelium as well as in the examined URT and salivary gland tissues, which was also shared by the B.1.1.7 virus. Conclusions In our analyses, we highlighted the active role of these anatomic sites in coronavirus disease 2019.
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Lungu, Claudiu N., Melinda E. Füstös, Ireneusz P. Grudziński, Gabriel Olteanu, and Mihai V. Putz. "Protein Interaction with Dendrimer Monolayers: Energy and Surface Topology." Symmetry 12, no. 4 (April 17, 2020): 641. http://dx.doi.org/10.3390/sym12040641.
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Protein interaction with polymers layers is a keystone in designing bio-nano devices. Polyamidoamines (PAMAMs) are well-known polymers. Zero aromatic core dendrimers (ZAC) are molecules with no proven toxic effect in cultured cells. When coating nanodevices with enzymatic systems, active sites are disturbed by an interaction with the biosystem surface. Computational methods were used in order to simulate, characterize, and quantify protein–polymer interaction. Protein corona, i.e., surface proteins disposed on a viral membrane or nanodevice outer surface, are crucial in interactions with a potential pharmacological target or receptor. Corona symmetry has been observed in the Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a protein alpha 1 antitrypsin’s a crystallographic structure was chosen. Protein–mono dendrimer layer systems were generated using in silico methods in order to simulate their interaction. Interactions were quantified using topological and quantum mechanical strategies. Results showed that PAMAM and ZAC interact differently with alpha 1 antitrypsin. Energy and topological surfaces of protein vary accordingly with the dendrimer monolayer. Topological surfaces have a higher sensibility in describing the interactions.
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Rajasekharan, Sreejith, Rafaela Milan Bonotto, Lais Nascimento Alves, Yvette Kazungu, Monica Poggianella, Pamela Martinez-Orellana, Natasa Skoko, Sulena Polez, and Alessandro Marcello. "Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2." Viruses 13, no. 5 (April 30, 2021): 808. http://dx.doi.org/10.3390/v13050808.
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Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious viruses. The mechanism resides in the inhibitory activity toward α-glucosidases that are involved in the early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19.
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Priyandoko, Didik, Wahyu Widowati, Mawar Subangkit, Diana Jasaputra, Teresa Wargasetia, Ika Sholihah, and Jenifer Aviani. "Molecular Docking Study of the Potential Relevance of the Natural Compounds Isoflavone and Myricetin to COVID-19." International Journal Bioautomation 25, no. 3 (September 2021): 271–82. http://dx.doi.org/10.7546/ijba.2021.25.3.000796.
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The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly from its origin in Wuhan City, Hubei Province, China, to the rest of the world. The efficacy of herbal treatment in the control of contagious disease was demonstrated during the 2003 outbreak of severe acute respiratory syndrome (SARS). Natural compound used for this study were isoflavone and myricetin. Molecular docking was performed to analyze binding mode of the compounds towards 12 proteins related to COVID-19. The prediction shows that isoflavone and myricetin have moderate probability of antiviral activity. All of the docked compounds occupied the active sites of the proteins related to COVID-19. Based on QSAR and molecular docking, interactions were predicted with 10 out of 12 potential COVID-19 proteins for myricetin and with 9 out of 12 proteins interactions for isoflavone. A potential disease alleviating action is suggested for isoflavone and myricetin in the context of COVID-19 infection.
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Nakayoshi, Tomoki, Koichi Kato, Eiji Kurimoto, and Akifumi Oda. "Virtual Alanine Scan of the Main Protease Active Site in Severe Acute Respiratory Syndrome Coronavirus 2." International Journal of Molecular Sciences 22, no. 18 (September 11, 2021): 9837. http://dx.doi.org/10.3390/ijms22189837.
Full textAbstract:
Recently, inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) have been proposed as potential therapeutic agents for COVID-19. Studying effects of amino acid mutations in the conformation of drug targets is necessary for anticipating drug resistance. In this study, with the structure of the SARS-CoV-2 Mpro complexed with a non-covalent inhibitor, we performed molecular dynamics (MD) simulations to determine the conformation of the complex when single amino acid residue in the active site is mutated. As a model of amino acid mutation, we constructed mutant proteins with one residue in the active site mutated to alanine. This method is called virtual alanine scan. The results of the MD simulations showed that the conformation and configuration of the ligand was changed for mutants H163A and E166A, although the structure of the whole protein and of the catalytic dyad did not change significantly, suggesting that mutations in His163 and Glu166 may be linked to drug resistance.
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Donadel, Marcelo Menegotto, Lucas Montiel Petry, Carolina Boeira Soares, Laura de Castro e. Garcia, Luana Braga Bittencourt, and Luiz Carlos Bodanese. "Analysis of the impact of pronation maneuver in patients on mechanical ventilation with diagnosis of pneumonia by Covid-19 and acute respiratory distress syndrome." Brazilian Journal of Health Review 5, no. 6 (December 9, 2022): 24053–64. http://dx.doi.org/10.34119/bjhrv5n6-175.
Full textAbstract:
Objective: To analyze the profile of patients on invasive mechanical ventilation with SARS-CoV-2 pneumonia who were pronated and who developed acute respiratory distress syndrome. Methods: Historical cohort study through the analysis of a database containing 282 patients hospitalized in a large university hospital in the city of Porto Alegre, Brazil. The population studied included individuals infected with SARS-CoV-2 and with a clinical course marked by severe pneumonia and, mainly, by acute respiratory distress syndrome, submitted to mechanical ventilation and invasive pronation maneuver. Results: Database analysis showed a high mortality rate for all patient groups and a high case fatality rate, especially in elderly patients and in individuals with active oncologic disease or with chronic kidney disease. Conclusions: The high overall mortality rate, as well as the high lethality, especially in elderly patients and in individuals with active oncologic disease or with chronic kidney disease, suggests that, for certain specific population groups, the prone maneuver is not effective in reducing high. mortality caused by acute respiratory distress syndrome associated with COVID-19.
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Denisov, M. S., and Ya A. Beloglazova. "Anticoronaviral activity of triterpenoids." Biomedical Chemistry: Research and Methods 3, no. 2 (2020): e00127. http://dx.doi.org/10.18097/bmcrm00127.
Full textAbstract:
The discovery and investigations of new therapeutic agents with anticoronaviral activity is extremely important due to the COVID-19 pandemic caused by the SARS-CoV-2 virus. Currently, there are no anti-COVID-19 drugs, characterized by efficacy which has been proved in correspondence with criteria of evidence-based medicine. However, there are some anti SARS-CoV-2 drugs, acting on the other Coronaviridae family member causing SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). Consequently, a wide range of organic substances of synthetic and natural origin were studied for the anticoronaviral activity. The review summarizes and systematizes the literature data on the anti-coronavirus activity of triterpenoids. The structural features of triterpenoids, which are important for the mechanisms of anticoronaviral activity, are discussed. The structures of the most active compounds are presented. The material is classified by approaches to study the anticoronaviral activity of individual substances or plants extracts. Recommendations for the further research of triterpenoids anticoronaviral activity are given.
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Snow-Smith, Maryonne, Paul J. Baker, Andrea C. Bohrer, Ehydel Castro, Flor Torres-Juarez, Charles F. Anderson, Michelle M. Makiya, Irini Sereti, Amy D. Klion, and Katrin D. Mayer-Barber. "Investigating a Role for Eosinophils in the Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 73.10. http://dx.doi.org/10.4049/jimmunol.210.supp.73.10.
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Abstract Eosinophils rapidly decrease in the peripheral blood of patients during COVID-19, and eosinopenia has been correlated with disease severity. These clinical observations suggest that eosinophils may play a functional role in the response to SARS-CoV-2 infection. Murine studies have shown that eosinophils can be recruited to the lungs in response to infection with respiratory viruses, including RSV and influenza and parainfluenza viruses, yet the role of eosinophils in the lungs in response to SARS-CoV-2 infection is unknown. Here, we used a two-pronged approach employing mouse models of SARS-CoV-2 infection to study the role of eosinophils in the antiviral immune response and viral control and clinical samples to assess eosinophilia and eosinophil activation in patients during and after COVID-19. Our initial findings indicate that eosinophils are recruited to the lungs after SARS-CoV-2 infection in mice and that eosinophil-deficient mice may have increased lung viral titers early after infection. In keeping with this hypothesis, serum levels of eosinophil granule proteins (a marker of tissue eosinophilia) were increased during active SARS-CoV-2 infection in patients participating in a long-term follow-up study of COVID-19, at a time when eosinophil counts were depressed. These preliminary data suggest that eosinophils may have a protective role in early anti-viral host defense during SARS-CoV-2 infection in mice and that further studies are required to better understand the relative roles of eosinophils in protection and pathology to SARS-CoV-2 infection. Funding for this study was provided in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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Shobiroh Nuur'Alimah, Agnia Nurul Jannati, Laksmi Ambarsari, and Syamsul Falah. "In silico study: molecular docking of SARS-Cov-2 endoribonuclease on active compounds of Gmelina arborea Roxb. bark." E-Journal Menara Perkebunan 92, no. 1 (April 30, 2024): 70–81. http://dx.doi.org/10.22302/iribb.jur.mp.v92i1.561.
Full textAbstract:
Infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) triggers COVID-19 disease of the respiratory tract similar to pneumonia. The virus encodes four structural proteins and 16 non-structural proteins (nsp), one of which includes nsp15 or endoribonuclease (NendoU). NendoU plays an important role in viral replication and transcription and reduces the stimulation of immune cell responses. Active compounds in Gmelina arborea Roxb. bark have antioxidant properties that can inhibit the NendoU activity of SARS-CoV-2. This study aims to analyze the potential of compounds from Gmelina arborea Roxb. bark in inhibiting SARS-CoV-2 NendoU within in silico using the YASARA structure application. Balnophonin is the best test ligand based on binding ΔG value, dissociation constant (Kd), prediction of physicochemical characteristics, pharmacokinetics, and toxicity. Therefore, balanophonin can be developed as an effective alternative drug to inhibit SARS CoV-2 NendoU.
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Sada, Mitsuru, Takeshi Saraya, Haruyuki Ishii, Kaori Okayama, Yuriko Hayashi, Takeshi Tsugawa, Atsuyoshi Nishina, et al. "Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico." Microorganisms 8, no. 10 (October 20, 2020): 1610. http://dx.doi.org/10.3390/microorganisms8101610.
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Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.
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Citarella, Andrea, Alessandro Dimasi, Davide Moi, Daniele Passarella, Angela Scala, Anna Piperno, and Nicola Micale. "Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives." Biomolecules 13, no. 9 (September 2, 2023): 1339. http://dx.doi.org/10.3390/biom13091339.
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The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.
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Bedford, Trevor, Alexander L. Greninger, Pavitra Roychoudhury, Lea M. Starita, Michael Famulare, Meei-Li Huang, Arun Nalla, et al. "Cryptic transmission of SARS-CoV-2 in Washington state." Science 370, no. 6516 (September 10, 2020): 571–75. http://dx.doi.org/10.1126/science.abc0523.
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After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.
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Shigeta, Shiro, and Toshihiro Yamase. "Current Status of Anti-SARS Agents." Antiviral Chemistry and Chemotherapy 16, no. 1 (February 2005): 23–31. http://dx.doi.org/10.1177/095632020501600103.
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Severe acute respiratory syndrome (SARS) is a disease that has newly emerged in the 21st century, and is both severe and highly contagious. SARS first surfaced in late 2002 and spread within a few months from its origin in Guandong province, China, to more than 30 countries (World Health Organization, 2003). In this review, several antiviral substances shown to be active in vitro will be introduced and summarized in the order of the virus' replication steps; that is, binding to cellular receptor, fusion and entry to the cells, viral RNA replication and transcription, protein processing and so on. The possible clinical use of several synthetic peptides, including those that mimic the S-binding domain, the HR2 fusion protein and SARS proteinase substrates, will be discussed. Monoclonal antibodies (Mabs) and established drugs, such as interferons and HIV proteinase inhibitors, are also discussed in relation to anti-SARS clinical use.
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Kullappan, Malathi, Jenifer M Ambrose, and Surapaneni Krishna Mohan. "Lead Identification for Severe Acute Respiratory Syndrome Coronavirus-2 Spike D614G Variant of COVID-19: A virtual Screening Process." Biomedical and Pharmacology Journal 14, no. 4 (December 30, 2021): 1929–39. http://dx.doi.org/10.13005/bpj/2291.
Full textAbstract:
COVID-19, a pandemic disease caused by single-stranded RNA virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The structural spike (S) protein of SARS-CoV-2 plays a vital role in host cell entry, where the Angiotensin-Converting Enzyme-2 (ACE2) receptor of the human cell binds to the Receptor Binding Domain (RBD) region of the S1 domain and makes cell entry. The binding affinity of SARS-CoV-2-ACE2 is tenfold higher than the SARS-CoV-1-ACE2. Recent studies expose that the SARS-CoV-2 S D614G variant is highly infectious than D614 protein, also the D614G variant is highly stable than D614. So far, there is no effective viral-specific regimen for COVID-19. To overcome such problems, in our study, we have utilized the ZINC database to screen potent leads against the highly transmitting SARS-CoV-2 spike D614G protein, through a virtual screening procedure. We have applied three computational tools iGEMDOCK server, AutoDock version 4.2.6 and admetSAR to get active leads. The ZINC000150588351 (Elbasvir), ZINC000064540179 (Sofosbuvir analogue) and ZINC000137700912 (Sofosbuvir analogue) molecules have a greater binding affinity with the high binding energies of -8.22 kcal/mol, -8.13 kcal/mol and -7.64 kcal/mol respectively. The molecules ZINC000064540179 and ZINC000137700912 have high binding energy than their core molecule Sofosbuvir (ZINC100074252) of -4.06 kcal/mol. The ADMET prediction of these molecules reveals satisfactory human intestinal absorption and non-mutagenic property. Our results deliver valuable contributions to the design of inhibitors against COVID-19.
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Ożarowski, Marcin, and Tomasz M. Karpiński. "The Effects of Propolis on Viral Respiratory Diseases." Molecules 28, no. 1 (January 1, 2023): 359. http://dx.doi.org/10.3390/molecules28010359.
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Propolis remains an interesting source of natural chemical compounds that show, among others, antibacterial, antifungal, antiviral, antioxidative and anti-inflammatory activities. Due to the growing incidence of respiratory tract infections caused by various pathogenic viruses, complementary methods of prevention and therapy supporting pharmacotherapy are constantly being sought out. The properties of propolis may be important in the prevention and treatment of respiratory tract diseases caused by viruses such as severe acute respiratory syndrome coronavirus 2, influenza viruses, the parainfluenza virus and rhinoviruses. One of the main challenges in recent years has been severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19. Recently, an increasing number of studies are focusing on the activity of various propolis preparations against SARS-CoV-2 as an adjuvant treatment for this infection. Propolis has shown a few key mechanisms of anti-SARS-CoV-2 action such as: the inhibition of the interaction of the S1 spike protein and ACE-2 protein; decreasing the replication of viruses by diminishing the synthesis of RNA transcripts in cells; decreasing the particles of coronaviruses. The anti-viral effect is observed not only with extracts but also with the single biologically active compounds found in propolis (e.g., apigenin, caffeic acid, chrysin, kaempferol, quercetin). Moreover, propolis is effective in the treatment of hyperglycemia, which increases the risk of SARS-CoV-2 infections. The aim of the literature review was to summarize recent studies from the PubMed database evaluating the antiviral activity of propolis extracts in terms of prevention and the therapy of respiratory tract diseases (in vitro, in vivo, clinical trials). Based upon this review, it was found that in recent years studies have focused mainly on the assessment of the effectiveness of propolis and its chemical components against COVID-19. Propolis exerts wide-spectrum antimicrobial activities; thus, propolis extracts can be an effective option in the prevention and treatment of co-infections associated with diseases of the respiratory tract.
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Jugler, Collin, Haiyan Sun, and Qiang Chen. "SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody." Vaccines 9, no. 11 (November 20, 2021): 1365. http://dx.doi.org/10.3390/vaccines9111365.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute respiratory distress syndrome. In this study, we explored the feasibility of using plants to produce an anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) and examined its utility in reducing IL-6 signaling in an in vitro model, which simulates IL-6 induction during SARS-CoV-2 infection. The anti-IL6R mAb (IL6RmAb) was quickly expressed and correctly assembled in Nicotiana benthamiana leaves. Plant-produced IL6RmAb (pIL6RmAb) could be enriched to homogeneity by a simple purification scheme. Furthermore, pIL6RmAb was shown to effectively inhibit IL-6 signaling in a cell-based model system. Notably, pIL6RmAb also suppressed IL-6 signaling that was induced by the exposure of human peripheral blood mononuclear cells to the spike protein of SARS-CoV-2. This is the first report of a plant-made anti-IL-6R mAb and its activity against SARS-CoV-2-related cytokine signaling. This study demonstrates the capacity of plants for producing functionally active mAbs that block cytokine signaling and implies their potential efficacy to curb cytokine storm in COVID-19 patients.
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Salman, Saad, Fahad Hassan Shah, Maham Chaudhry, Muniba Tariq, Muhammad Yasir Akbar, and Muhammad Adnan. "In silico analysis of protein/peptide-based inhalers against SARS-CoV-2." Future Virology 15, no. 9 (September 2020): 557–64. http://dx.doi.org/10.2217/fvl-2020-0119.
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Aim: Peptide/protein-based inhalers are excessively used to treat respiratory disorders. The molecular docking was performed for these inhalers including human neutralizing S230 light chain-antibody (monoclonal antibodies [mAbs]), alpha-1-antitrypsin (AAT), short-palate-lung and nasal-epithelial clone-1-derived peptides (SPLUNC1) and dornase-alfa (DA) against spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to assess their inhibitory activity. Materials & methods: HawkDock was used to dock these biologics against SARS-CoV-2 spike-glycoprotein. Results: Results showed that DA, AAT and mAb were quite active against spike glycoprotein with a binding free energy of -26.35 and -22.94 kcal/mol. Conclusion: mAB and AAT combined with DA can be used in the treatment of coronavirus disease of 2019 as a potential anti-SARS-CoV-2 agent.
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Zhong, Nan, Shengnan Zhang, Peng Zou, Jiaxuan Chen, Xue Kang, Zhe Li, Chao Liang, Changwen Jin, and Bin Xia. "Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain." Journal of Virology 82, no. 9 (February 27, 2008): 4227–34. http://dx.doi.org/10.1128/jvi.02612-07.
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ABSTRACT The main protease (Mpro) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. It was found that SARS-CoV Mpro exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. However, the mechanism of SARS-CoV Mpro dimerization, especially the roles of its N-terminal seven residues (N-finger) and its unique C-terminal domain in the dimerization, remain unclear. Here we report that the SARS-CoV Mpro C-terminal domain alone (residues 187 to 306; Mpro-C) is produced in Escherichia coli in both monomeric and dimeric forms, and no exchange could be observed between them at room temperature. The Mpro-C dimer has a novel dimerization interface. Meanwhile, the N-finger deletion mutant of SARS-CoV Mpro also exists as both a stable monomer and a stable dimer, and the dimer is formed through the same C-terminal-domain interaction as that in the Mpro-C dimer. However, no C-terminal domain-mediated dimerization form can be detected for wild-type SARS-CoV Mpro. Our study results help to clarify previously published controversial claims about the role of the N-finger in SARS-CoV Mpro dimerization. Apparently, without the N-finger, SARS-CoV Mpro can no longer retain the active dimer structure; instead, it can form a new type of dimer which is inactive. Therefore, the N-finger of SARS-CoV Mpro is not only critical for its dimerization but also essential for the enzyme to form the enzymatically active dimer.
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Dhakad, Prashant Kumar, Raghav Mishra, and Isha Mishra. "A Concise Review: Nutritional Interventions for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)." Natural Resources for Human Health 3, no. 4 (November 18, 2023): 403–25. http://dx.doi.org/10.53365/nrfhh/175070.
Full textAbstract:
Wuhan, China reported a novel coronavirus-related sickness in late 2019, which quickly spread into a global epidemic. One crucial factor in combating the coronavirus infection appears to be the presence of a robust, long-lasting, and active immune system. The immune response is affected by several factors, including food. Nutritional insufficiency can cause immune deficits, making infections more likely to cause fatality. Thus, understanding numerous behaviors, particularly dietary habits, is essential to determining their capacity to reduce severe acute respiratory syndrome coronavirus 2 risks and improve prognosis. In this paper, the authors summarize the complex interaction between nutritional status and severe acute respiratory syndrome corona virus 2 infections, as well as the consequences of poor nutrients with regard of the extent to which disease is affected. The literature was compiled by searching a number of reputable scientific databases including Scopus, Science Direct, Springer, Nature, PubMed, Web of Science resources. The accumulating evidence demonstrates that malnutrition impairs the immune system's ability to function, weakening the body's infection resistance. This review emphasizes the significance of nutritional status in the care of coronavirus disease patients as well as demonstrates that functional foods may contribute to better outcomes. Ageing, Obesity, Malnutrition, Undernutrition, Lack of exercise are having a devastating effect on people's health in general and during this coronavirus disease. The severity and prognosis of coronavirus illness seem to be significantly influenced by lifestyle choices, nutritional imbalances, and impaired immune response.
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Salman, Saad, Fahad H. Shah, Jawaria Idrees, Fariha Idrees, Shreya Velagala, Johar Ali, and Abid A. Khan. "Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-CoV-2 inhibitors." Future Virology 15, no. 5 (May 2020): 267–75. http://dx.doi.org/10.2217/fvl-2020-0079.
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Aim: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a pernicious viral disease, causes acute respiratory distress responsible for mortality and morbidity worldwide. To screen different immunomodulatory medicinal compounds to unravel their interaction with SARS-CoV-2 viral proteins. Materials & methods: A library of immunomodulatory medicinal compounds with antiviral capability were analyzed against SARS proteases, spike protein and nonstructural proteins (NSP-9, 15) using Autodock vina. Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Further ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis showed good pharmacokinetic properties and low acute toxicity of these compounds. Conclusion: The current study provides convincing evidence that these medicinal compounds exert antiviral activity against the SARS-CoV-2 virus and could be further exploited for the treatment of this disease.
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Pignolo, Antonia, Maria Aprile, Cesare Gagliardo, Giovanni Maurizio Giammanco, Marco D’Amelio, Paolo Aridon, Giuseppe La Tona, Giuseppe Salemi, and Paolo Ragonese. "Clinical Onset and Multiple Sclerosis Relapse after SARS-CoV-2 Infection." Neurology International 13, no. 4 (December 6, 2021): 695–700. http://dx.doi.org/10.3390/neurolint13040066.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with several neurological disorders including headache, facial palsy, encephalitis, stroke, demyelinating disorders. The present report will discuss cases of multiple sclerosis (MS) onset and relapse both beginning early after SARS-CoV-2 infection. In both cases, magnetic resonance imaging (MRI) showed widespread bilateral subcortical and periventricular active lesions. Serum IgG against SARS-CoV-2 Spike antigens confirmed seroconversion with titers that are considered not definitely protective against possible reinfection. We hypothesize that SARS-CoV-2 infection, as previously reported for other viruses, could drive an active inflammatory response that can contribute either to the onset of MS or its relapse. The presented data further support the importance of vaccination in individuals with MS.
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Gordon, Calvin J., Egor P. Tchesnokov, Emma Woolner, Jason K. Perry, Joy Y. Feng, Danielle P. Porter, and Matthias Götte. "Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency." Journal of Biological Chemistry 295, no. 20 (April 13, 2020): 6785–97. http://dx.doi.org/10.1074/jbc.ra120.013679.
Full textAbstract:
Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum antiviral activity against RNA viruses, and previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV) have revealed that delayed chain termination is RDV's plausible mechanism of action. Here, we expressed and purified active SARS-CoV-2 RdRp composed of the nonstructural proteins nsp8 and nsp12. Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA. Incorporation of RDV-TP at position i caused termination of RNA synthesis at position i+3. We obtained almost identical results with SARS-CoV, MERS-CoV, and SARS-CoV-2 RdRps. A unique property of RDV-TP is its high selectivity over incorporation of its natural nucleotide counterpart ATP. In this regard, the triphosphate forms of 2′-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.
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Pratapa, Sree Karthik, Sourya Acharya, Sai Spoorthy Mamidipalli, and Amol Andhale. "Caring for Cancer Patients during Corona Pandemic—(COVID-19)—A Narrative Review." South Asian Journal of Cancer 10, no. 01 (January 2021): 19–22. http://dx.doi.org/10.1055/s-0040-1721292.
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Abstract Background Coronavirus disease 2019, the third pandemic of 21st century which has brought the whole world under panic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a zoonotic beta coronavirus sharing phylogenetic, genomic similarities with SARS virus and Middle East Respiratory Syndrome virus. Specific Concerns Cancer patients are at double the risk than normal patients since these patients are at immunocompromised state. WHO guidelines advice the patients to plan only emergency hospital visits only till the pandemic persists. Should meet patient/visitors in a well-ventilated room or outdoors and maintain at least 2 m distance between the visitor/patients. It also encourages the patient to refill the prescribed medications in well advance and to stay physically active, if possible. Discussion The World Health Organizations’ isolate, trace, test, treat policy needs to be followed to protect these high-risk patients from this global pandemic.]
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Wang, Wenxiang, Ce Yang, Jing Xia, Ning Li, and Wei Xiong. "Luteolin is a potential inhibitor of COVID-19: An in silico analysis." Medicine 102, no. 38 (September 22, 2023): e35029. http://dx.doi.org/10.1097/md.0000000000035029.
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The severe respiratory syndrome 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread explosively, raising global health concerns. Luteolin shows antiviral properties, but its effect on SARS-CoV-2 and the associated mechanisms are not elucidated. We used network pharmacology, molecular docking and molecular dynamics to provide potential molecular support of luteolin (3,4,5,7-tetrahydroxyflavone) (LUT) against COVID-19. We employed network pharmacology, molecular docking, and molecular dynamics techniques to investigate how LUT affected COVID-19. Several databases were queried to determine potential target proteins related to LUT and COVID-19. Protein-protein interaction network was constructed, and core targets were filtered by degree value. Following that, functional enrichment was conducted. Molecular docking was utilized to ensure LUT was compatible with core target proteins. Finally, molecular dynamics was used to analyze the effects of the LUT on the optimal hub target. A total of 64 potential target genes for treating COVID-19 were identified, of which albumin, RAC-alpha serine/threonine-protein kinase, caspase-3, epidermal growth factor receptor, heat shock protein HSP 90-alpha, and mitogen-activated protein kinase 1 might be the most promising. In addition, molecular docking results showed that LUT could interact with SARS-CoV-2 major protease 3CL. LUT can bind to the active sites of 3CL protease and mitogen-activated protein kinase 1, showing an anti-SARS-CoV-2 potential.
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Elaiw, Ahmed, Abdualla Alsaedi, Aatef Hobiny, and Shaban Aly. "Global Properties of a Diffusive SARS-CoV-2 Infection Model with Antibody and Cytotoxic T-Lymphocyte Immune Responses." Mathematics 11, no. 1 (December 29, 2022): 190. http://dx.doi.org/10.3390/math11010190.
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A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to morbidity and mortality. SARS-CoV-2 infects the epithelial cells of the respiratory tract and causes coronavirus disease 2019 (COVID-19). The immune system’s response plays a significant role in viral progression. This article develops and analyzes a system of partial differential equations (PDEs), which describe the in-host dynamics of SARS-CoV-2 under the effect of cytotoxic T-lymphocyte (CTL) and antibody immune responses. The model characterizes the interplay between six compartments, healthy epithelial cells (ECs), latent infected ECs, active infected ECs, free SARS-CoV-2 particles, CTLs, and antibodies. We consider the logistic growth of healthy ECs. We first investigate the properties of the model’s solutions, then, we calculate all steady states and determine the conditions of their existence and global stability. The global asymptotic stability is examined by constructing Lyapunov functions. The analytical findings are supported via numerical simulations.
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Saad-Roy, Chadi M., Caroline E. Wagner, Rachel E. Baker, Sinead E. Morris, Jeremy Farrar, Andrea L. Graham, Simon A. Levin, Michael J. Mina, C. Jessica E. Metcalf, and Bryan T. Grenfell. "Immune life history, vaccination, and the dynamics of SARS-CoV-2 over the next 5 years." Science 370, no. 6518 (September 21, 2020): 811–18. http://dx.doi.org/10.1126/science.abd7343.
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The future trajectory of the coronavirus disease 2019 (COVID-19) pandemic hinges on the dynamics of adaptive immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, salient features of the immune response elicited by natural infection or vaccination are still uncertain. We use simple epidemiological models to explore estimates for the magnitude and timing of future COVID-19 cases, given different assumptions regarding the protective efficacy and duration of the adaptive immune response to SARS-CoV-2, as well as its interaction with vaccines and nonpharmaceutical interventions. We find that variations in the immune response to primary SARS-CoV-2 infections and a potential vaccine can lead to markedly different immune landscapes and burdens of critically severe cases, ranging from sustained epidemics to near elimination. Our findings illustrate likely complexities in future COVID-19 dynamics and highlight the importance of immunological characterization beyond the measurement of active infections for adequately projecting the immune landscape generated by SARS-CoV-2 infections.
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Gorbunov, A. A., L. E. Sorokina, D. V. Chegodar, A. V. Kubyshkin, and I. I. Fomochkina. "COVID-19 DIAGNOSTICS: CURRENT STATE OF THE PROBLEM AND PROSPECTS IN THE BRANCH." Crimea Journal of Experimental and Clinical Medicine 10, no. 2 (2020): 69–77. http://dx.doi.org/10.37279/2224-6444-2020-10-2-69-77.
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SARS-CoV-2 is a new representative of the world of virology related to coronaviruses and can cause a wide range of diseases of the respiratory system: from colds to acute respiratory distress-syndrome with severe respiratory failure. The pathogenesis of a new coronavirus infection (COVID-19) is associated with the ability of SARS-CoV-2 to bind to ACE receptors and subsequently activate IL-6, the main stimulator of the “cytokine storm”. Due to such features of the viral pathogenesis, early and accurate detection of active forms, as well as virus carriage are needed. In review, the whole spectrum of the main diagnostic methods is represented, with a comparison of the effectiveness and con- ditional indication of COVID-19: from the currently used methods (RT-PCR, ELISA) to potentially possible (OT-LAMP, CRISPR), as well as those still under development (chemiluminescence).
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Singh, Akhilesh Vikram. "Potential of amentoflavone with antiviral properties in COVID-19 treatment." Asian Biomedicine 15, no. 4 (August 1, 2021): 153–59. http://dx.doi.org/10.2478/abm-2021-0020.
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Abstract Amentoflavone is one of the flavonoids that are known for their antiviral effects and many of them are predicted to have inhibitory effects against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome Coronavirus (MERS-CoV) enzymes 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro). Amentoflavone is a biflavonoid found in the herbal extracts of St. John's wort (Hypericum perforatum), Gingko biloba, Selaginella tamariscina, Torreya nucifera, and many other plants. Its pharmacological actions have been listed as antiviral, antibacterial, antioxidant, anti-inflammatory, antidiabetic, antidepressant, and neuroprotective. Molecular docking studies have found that amentoflavone binds strongly to the active site of the main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As conventional antiviral medications are met with limited success against coronavirus disease-2019 (COVID-19) and vaccines are one of the only weapons against COVID-19 in the pharmaceutical armamentarium, traditional medicines are being considered for the forefront battle against COVID-19. Clinical studies with Hypericum and Gingko extract as additional or alternative drugs/supplements are registered. Here we review the potential of amentoflavone, an active agent in both Hypericum and Gingko extract as an adjunct therapy for COVID-19. Its anti-inflammatory, antioxidant, and sepsis preventive actions could provide protection against the “cytokine storm.” Compared with the herbal extracts, which induce cytochrome P450 (CYP) and uridine 5′-diphospho (UDP)-glucuronosyltransferases (UGT) activity producing a negative herb–drug interaction, amentoflavone is a potent inhibitor of CYP3A4, CYP2C9, and UGT. Further studies into the therapeutic potential of amentoflavone against the coronavirus infection are warranted.
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Roy, Santanu, Prakash Chandra Ghosh, Mitali Bera, and Sananda Majumder. "Pulmonary involvement in multisystem inflammatory syndrome in children, a diagnostic conundrum: case series from a tertiary care hospital in eastern India." International Journal of Contemporary Pediatrics 9, no. 8 (July 25, 2022): 762. http://dx.doi.org/10.18203/2349-3291.ijcp20221861.
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In April 2020, a novel syndrome in children and adolescents, termed multisystem inflammatory syndrome in children (MIS-C), related to SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) infection was first described in the United Kingdom and Italy. In this case series, we analysed 6 patients who had moderate to severe respiratory system manifestations at presentation, closely resembling the acute infection. A retrospective analysis of 6 pediatric patients, diagnosed as MIS-C, presenting with predominant respiratory system manifestations between December 2020 to October 2021 was undertaken. All the 6 patients presented with fever and predominant respiratory symptoms which mainly included difficulty in breathing, while two patients had accompanying chest pain. Gastrointestinal symptoms were found to be the most common accompanying systemic involvement. The inflammatory markers were found to be deranged in all the patients. COVID-19 RT-PCR was negative and serology for COVID-19 IgG was positive in all the patients. All the patients were successfully discharged. All were followed up 1 month after discharge. Residual respiratory morbidity was found in none of them. Our case series highlights the importance of distinguishing active covid-19 infection from MIS-C especially in the setting of overlapping clinical features. Timely diagnosis of MIS-C will also prevent unnecessary antibiotic usage.
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Colarossi, Bianca. "How Our Healthcare System Failed During the SARS Outbreak." Sciential - McMaster Undergraduate Science Journal, no. 1 (November 25, 2018): 23–24. http://dx.doi.org/10.15173/sciential.v1i1.1921.
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Severe Acute Respiratory Syndrome (SARS) was an active pandemic in the spring of 2003, ravaging places such as Hong Kong and Canada. In Ontario, the healthcare system was extremely unprepared, hence resulting in a multitude of deaths, in which many were healthcare professionals. In contrast, Vancouver took the necessary precautions leading up to the outbreak, and the benefits of this can be seen in their low death toll. In the future, the Ontario healthcare system needs to learn from these mistakes by preparing personal protective equipment and educating healthcare professionals on proper infectious disease control protocol. This is a call to action for the Ontario healthcare system.
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Sasisekharan, Varun, Niharika Pentakota, Akila Jayaraman, Kannan Tharakaraman, Gerald N. Wogan, and Uma Narayanasami. "Orthogonal immunoassays for IgG antibodies to SARS-CoV-2 antigens reveal that immune response lasts beyond 4 mo post illness onset." Proceedings of the National Academy of Sciences 118, no. 5 (January 14, 2021): e2021615118. http://dx.doi.org/10.1073/pnas.2021615118.
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Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the current pandemic remains a field of immense interest and active research worldwide. Although the severity of acute infection may depend on the intensity of innate and adaptive immunity, leading to higher morbidity and mortality, the longevity of IgG antibodies, including neutralizing activity to SARS-CoV-2, is viewed as a key correlate of immune protection. Amid reports and concern that there is a rapid decay of IgG antibody levels within 1 mo to 2 mo after acute infection, we set out to study the pattern and duration of IgG antibody response to various SARS-CoV-2 antigens in asymptomatic and symptomatic patients in a community setting. Herein, we show the correlation of IgG anti-spike protein S1 subunit, receptor binding domain, nucleocapsid, and virus neutralizing antibody titers with each other and with clinical features such as length and severity of COVID-19 illness. More importantly, using orthogonal measurements, we found the IgG titers to persist for more than 4 mo post symptom onset, implying that long-lasting immunity to COVID-19 from infection or vaccination might be observed, as seen with other coronaviruses such as SARS and Middle East respiratory syndrome.
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Dawood, A. A. "Identification of Cytotoxic T-Cell and B-Cell Epitopes in the Nucleocapsid Phosphoprotein of SARS-COV-2 Using Immunoinformatics." Mikrobiolohichnyi Zhurnal 83, no. 1 (February 17, 2021): 78–86. http://dx.doi.org/10.15407/microbiolj83.01.078.
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Last December, a novel coronavirus emerged in Wuhan city, China. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a high intense acute respiratory syndrome with elevation mortality. Nucleocapsid phosphoprotein (NP) is one of the most structural proteins of the virus. NP possesses active immunogenicity for T-cell response. Because NP considered as a potential vaccine target, our study goal was to identify the cytotoxic T-cell (CTL) and B-cell epitopes inside NP peptides. Methods. We used a series of popular immunoinformatics and algorithm tools such as FASTA-NCBI, CLUSTAL-OMGA, T-COFFEE, SWISS-MODEL, CTLPred and its branches. Results. Homology modeling and alignment of SARS-CoV-2 NP showed high conserved residues compared with related sequences. Different types of the major histocompatibility complex (MHC) alleles were identified, specifically human leukocyte antigens (HLA-A) affinity for NP. We also demonstrate six B-cell epitopes with a high score above the threshold. Conclusions. We recorded high binder HLA-A*02:01 alleles matched between the novel coronavirus SARS-CoV-2 NP and the Bat coronavirus SARS-Bat-CoV NP. Identification of CTL response and B-cell predictions will be helpful in reverse immunogenetic approaches, hence in the strategy process of the plausible design of the vaccine.