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Journal articles on the topic "Antiviraux – Conception"
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Couvreur, Patrick. "La « squalénisation » : un exemple de conception de nanomédicaments anticancéreux et antiviraux." Bulletin de l'Académie Nationale de Médecine 193, no. 3 (March 2009): 663–74. http://dx.doi.org/10.1016/s0001-4079(19)32558-0.
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Hu, Zhao X., Yi N. Ye, Wei G. Wu, Xu J. Liang, Qi W. Wu, Ao Zhang, Xing R. Zheng, Zhi L. Gao, Liang Peng, and Chan Xie. "Real-Life State of Anti-Hepatitis B Virus Drug Choice in Child-Bearing Age Male Patients and Effect on Fertility and Fetal Safety." Canadian Journal of Gastroenterology and Hepatology 2019 (April 1, 2019): 1–8. http://dx.doi.org/10.1155/2019/9703907.
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Research on effects of anti-hepatitis B virus (HBV) nucleoside analogs on male fertility and birth defects is limited and safety of nucleoside analogs in pregnancy is still a concern. Chronic hepatitis B (CHB) patients in Guangdong province were surveyed using a structured questionnaire. We collected data including medication type, fertility, and birth defects. Moreover, a survey of the knowledge of antiviral nucleoside analogs safety in fertility of male patients was conducted among physicians nationwide. Semen samples of 30 patients were collected. We screened 1050 HBV-positive male patients. Reasons for not receiving antivirals in 150 patients were “did not meet criteria for antiviral therapy,” fertility, and financial. Furthermore, 900 participants received antivirals (85.71%, 900/1050), including 792 patients with children and 15.15% (120/792) took anti-HBV treatment when preparing for pregnancy. Based on whether they received antiviral therapy during conception or not, we divided patients into two groups. In the child-bearing age group, 88.33% (106/120) of patients received telbivudine (LDT), whereas the other group mainly received entecavir (ETV) (87.20%, 586/672). No significant difference occurred in birth defect incidence rates between both groups. Furthermore, 558 physicians completed questionnaires. Reasons that influenced drug selection were “patient’s condition,” “fertility demand,” “financial condition,” and “compliance.” Telbivudine was the first-choice drug (32.80%, 183/558) while tenofovir (TDF) was the second (2.69%, 15/558). Additionally, 61.47% of physicians considered telbivudine or tenofovir as the first choice for male patients who met antiviral criteria, whereas 19% suggested delayed therapy and follow-up until childbirth. No significant changes occurred in semen volume, concentration, mobility, and percentage before and after administration of anti-HBV nucleoside analogs, which did not affect male fertility and birth defect incidence while the desire for pregnancy influenced drug selection and timing of administration. Further research on the effects of analogs on male fertility and fetal safety is required.
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Bragina, E. E. "Viral infection of spermatozoa. Part 1. Hepatitis B virus and human papillomavirus (review)." Andrology and Genital Surgery 21, no. 4 (February 12, 2021): 12–19. http://dx.doi.org/10.17650/2070-9781-2020-21-4-12-19.
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Intragametal viral infection of spermatozoa can cause true vertical transmission of viruses through germ cells. Currently, human papilloma-virus, including oncogenic risk strains, and hepatitis B virus, have been detected in spermatozoa. The possibility of vertical transmission of hepatitis B virus and human papillomavirus has been proven.Intragametal infection of spermatozoa with viruses of human papillomavirus and hepatitis B virus leads to abnormalities in the development of the embryo and can cause spontaneous abortions both duringnatural conception and when using assisted reproductive technologies.The development of adequate methods for diagnosing an intragametal spermatozoa virus infection will make it possible to find out, at least in some patients, the cause of infertility and pregnancy abnormalities and apply appropriate antiviral therapy in preparation for natural conception or the use of assisted reproductive technologies.
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Bragina, E. E. "Viral infection of sperm. Part 2. Human herpes viruses, human immunodeficiency virus, hepatitis C virus, Zika virus (review)." Andrology and Genital Surgery 21, no. 4 (February 12, 2021): 20–30. http://dx.doi.org/10.17650/2070-9781-2020-21-4-20-30.
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Intragametal viral infection of spermatozoa can cause true vertical transmission of viruses through germ cells. Currently, human immunodeficiency virus, hepatitis C viruses, herpes simplex virus, cytomegalovirus, Zika virus have been detected in spermatozoa. The possibility of vertical transmission of human immunodeficiency virus, cytomegalovirus, herpes simplex virus and Zika virus has been proven.Intragametal infection of spermatozoa with viruses of the herpes group leads to abnormalities in the development of the embryo and can cause spontaneous abortions both during natural conception and when using assisted reproductive technologies.The development of adequate methods for diagnosing an intragametal spermatozoa virus infection will make it possible to find out, at least in some patients, the cause of infertility and pregnancy abnormalities and apply appropriate antiviral therapy in preparation for natural conception or the use of assisted reproductive technologies.
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Kovalyk, V. Р., V. V. Malinovskaya, A. N. Shuvalov, L. F. Kurilo, К. I. Yurlov, М. A. Gomberg, and A. A. Kushch. "Cytomegalovirus infection and male infertility: case report." Andrology and Genital Surgery 22, no. 1 (April 22, 2021): 85–89. http://dx.doi.org/10.17650/1726-9784-2021-22-1-85-89.
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Objectives. To present a case report of male infertility associated with cytomegalovirus infection and the outcome of antiviral treatment.Clinical observation. A 31-year-old man presented with a history of 6 years of infertility. No pathology was revealed in his wife. High loads of cytomegalovirus (CMV) were detected by PCR: in expressed prostatic secretion (EPS) 8700 copies/ml, in ejaculate – 598 440 copies/ml. Sperm examination revealed necrozoospermia and leukospermia. CMV-associated accessory gland infection was verified. The patient was treated with valacyclovir 500 bid for 90 days and interferon α2β suppository (Viferon®) 1 million IU for 30 days. All sperm parameters improved in 1 month after initiation of antiviral treatment. Sperm concentration and motility increased × 1.5 and × 1.4 respectively, sperm viability and leukocyte count achieved reference values. At the same time, CMV loads decreased: EPS to 300 copies/ml, the ejaculate to 54 000 copies/ml. After 3 months (by the end of the antiviral treatment): EPS-negative, the ejaculate – 6060 copies/ml; after 6 months: EPS – negative, the ejaculate 3900 copies/ml. Within 6 months, the woman became pregnant and gave birth to a healthy baby girl. After 3 years, there was a second pregnancy and the birth of a healthy boy.Conclusion. The male factor has been established as the cause of infertility in a married couple; the only probable etiological agent of pathozoospermia was cytomegalovirus infection. The use of complex antiviral and immunotherapy (interferon α2β with antioxidants, Viferon®) provided positive dynamics in clinical, sperm and laboratory parameters, which led to the conception and birth of two children.
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Déléris, Gérard. "Use of Organosilicon Compounds towards the Rational Design of Antiparasitic and Antiviral Drugs." Metal-Based Drugs 2, no. 3 (January 1, 1995): 143–51. http://dx.doi.org/10.1155/mbd.1995.143.
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One of the major problems met for the conception of antiviral or antiparasitic drugs is to reach a high level of selectivity towards the pathogenic agent versus the host. We shall describe two synthetic approaches where main group organometallics have been used towards this goal. A series of nucleoside sila-analogues was synthesized as potential therapeutic agents designed to inhibit HIV Reverse Transcriptase. In a second approach novel organosilicon derivatives have been synthesized as mimics of antisense oligonucleotides.Infectious agents, namely viruses or parasites, more or less use cellular machinery. Therefore therapeutic agents must interfere with biochemical mechanisms or possess high affinity towards specific molecular cellular components, to reach selectivity.We thought that main group organometallics could show many advantages for designing biologically active molecules in this field. They allow a high synthetic flexibility for the modulations of physico-chemical properties and they show a mechanistic behaviour which may be close to the one of several heteroelements present in living organisms such as sulfur or phosphorus.We tried to use this approach towards two directions involving the synthesis of organosilicon derivatives i.e:-the synthesis of organosilicon derivatives as inhibitors of HIV Reverse Transcriptase,-the synthesis of organosilicon precursors of modified antisense oligonucleotides.
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Rana, Ramesh, Rajkumar Dangal, Yogendra Singh, Ram Bahadur Gurung, Bhim Rai, and Amit Kumar Sharma. "Hepatitis C Virus Infection in Pregnancy and Children: Its Implications and Treatment Considerations with Directly Acting Antivirals: A Review." Journal of Nepal Medical Association 59, no. 241 (September 11, 2021): 942–53. http://dx.doi.org/10.31729/jnma.5501.
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Hepatitis C virus infection (HCV) is a global health problem affecting >71 million people worldwide with chronic hepatitis C, 40% reproductive age group, and 8% pregnant women. Intravenous drug abuse, multi-transfusions are major risk factors in adults, while vertical transmission in pediatric population. It commonly presents as a chronic liver disease, has higher risk of liver cirrhosis and even progression to hepatocellular carcinoma. Therefore, proper screening of high-risk populations including pregnancy is recommended. All diagnosed chronic hepatitis C cases should be treated with directly acting anti-virals (DAAs) including pre-conception which has a cure rate of >95%. This would reduce the disease burden, vertical transmission, and disability associated. However, no DAAs regimens recommendation till date due to lack of evidence on adverse fetal outcomes and are concerned about the pharmacokinetic effect regarding physiological changes during pregnancy. Therefore, in this review, we have tried to explore the possible use of DAAs regimens and their safety issues during pregnancy, and possible consideration of few pan-genotypic regimens in the late 2nd and early 3rd trimester. This would not only prevent vertical transmission and decrease disease burden but also help to meet the WHO 2030 target of HCV elimination as a major public health problem.
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Akbar, Sheikh Mohammad Fazle, Mamun Al Mahtab, Sakirul Khan, Osamu Yoshida, and Yoichi Hiasa. "Development of Therapeutic Vaccine for Chronic Hepatitis B: Concept, Cellular and Molecular Events, Design, Limitation, and Future Projection." Vaccines 10, no. 10 (September 30, 2022): 1644. http://dx.doi.org/10.3390/vaccines10101644.
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Four decades have passed since the first usage of the therapeutic vaccine in patients with chronic hepatitis B (CHB). However, there is no approved regimen of vaccine therapy for the treatment of CHB. This is mainly attributable to faulty conception, an improper understanding of the cellular and molecular mechanisms of CHB, and the impaired design of vaccine therapy for CHB. With the advent of new techniques and a better understanding of cellular and molecular mechanisms underlying the genesis of CHB, the limitations and failures of previous regimens of therapeutic vaccines have been primarily understood. Additionally, the importance of immune therapy for treating millions of CHB patients and achieving the target of “Elimination of Hepatitis by 2030” has been focused on in the international arena. This has been amplified by the apparent limitation of commercially available antiviral drugs that are infinite in duration, endowed with safety concerns, and unable to cure liver damage due to their minimal immune modulation capacities. The proposed review article comprehensively discusses each of these points and proposes evidence-based approaches for viable types of vaccine therapy for the treatment of CHB.
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Lopes Araújo, Daniel, José Eufrazino Júnior, Vinicius Santos Silva, Carla Franco Mendonça de Araújo, Thaynara Hevellin Evangelista, Hilary Hevellin Evangelista, Geovana Maciel Lima, et al. "AVALIAÇÃO DO POTENCIAL TRIPANOCIDA DE DERIVADOS TIOSSEMICARBAZONAS: UMA REVISÃO." RECIMA21 - Revista Científica Multidisciplinar - ISSN 2675-6218 2, no. 9 (October 11, 2021): e29658. http://dx.doi.org/10.47820/recima21.v2i9.658.
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Neglected diseases are a group of communicable diseases that mainly affect tropical regions in developing countries. Among this group of diseases is Chagas disease, which has been classified among the six most important parasitic diseases in the world, and it is estimated that more than one billion people are at risk in countries that are considered endemic. The aim of this study is to conduct a literature review on the trypanocidal activity of thiosemicarbazone derivatives. The study is a review research that used 31 articles to highlight the scientific findings on the trypanocidal activity of the derivatives in question. Articles were included in the time estimate between 2010 - 2021 (last 12 years). The search and selection of the reference studies was performed in Scielo, Science Direct, PubMed and Google Academic databases. The literature highlights that thiosemicarbazones are considered privileged compounds with a wide scientific interest due to their diverse chemical and biological properties, such as: antitumor, antibacterial, antiviral, antiprotozoal, and anti-chagasic. The studies presented here, which demonstrate the investigations of compounds of this class and their derivatives, are an important step towards the conception of therapeutic methods against Trypanosoma cruzi. New studies are necessary to elucidate in an even more specific way the effects of these derivatives in vivo, in order to obtain an alternative pharmacological therapy for Chagas disease.
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Kagramanova, Zh A., P. E. Lanshchakova, V. V. Malinovskaya, A. A. Svistunov, and E. N. Vizhlova. "Correlations in the pathogenesis by early pregnancy loss." Voprosy ginekologii, akušerstva i perinatologii 20, no. 4 (2021): 45–54. http://dx.doi.org/10.20953/1726-1678-2021-4-45-54.
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Objective. To improve the quality of life and outcome by consecutive pregnancy in patients based on the analysis of correlations and differences in markers for the diagnosis by early pregnancy loss (EPL) in early gestation period (up to 12 weeks). Patients and methods. 100 patients aged 18 to 40 years diagnosed with early pregnancy loss (EPL) at 7–8 and 9–10 weeks of obstetric term were examined. The types of EPL were identified by ultrasound criteria; correlations and differences in the EPL mechanism during early pregnancy were determined. Time characteristics of the gestational sac (GS) development from conception to miscarriage and the duration of persistence of an empty sac in the uterine cavity before the diagnosis of EPL were recorded. Molecular genetic testing of the chorion in 42 women with EPL was performed by multi-locus quantitative fluorescent polymerase chain reaction (PCR). The method of manual vacuum aspiration under the control of hysteroscopy was developed, followed by the administration of antibacterial, antiviral, and immunomodulatory therapy with Viferon® rectal suppositories at a dose of 1,000,000 IU 1 suppository twice a day at 12-hour intervals for 10 days and Viferon® gel 36,000 IU on the vaginal region of the cervix at a dose of 2 mL twice a day for 7 days. Results. The period of hospital admission for patients with embryonic miscarriage (EM) as the type of EPL prevailed between 8 and 10 weeks, on the average – 9.5 weeks of obstetric term, in contrast to empty sac (ES, 7–8 weeks). The period of the GS development in ES ranged from 17 to 36 days (2.3 to 5.1 weeks); in EM – 4 to 9 weeks (26 to 69 days) in 96% of patients, and the embryo development was from 3–4 to 6–7 weeks from conception (21 to 49 days). There was a 1.2-week difference in the desynchronization of the development of GS and an embryo. A significant positive correlation between gestational age (before diagnosis) and β-hCG levels (26,348 ± 18,289 mIU/mL) in patients without bloody discharge at the time of hospitalization was observed. However, there was a desynchronization of lag in β-hCG levels by an average of 3 times (8661 ± 7701 mIU/mL) in the presence of bloody discharge, although the sizes of GS according to mean sac diameter (MSD) were comparable (28 ± 13 mm and 30 ± 11 mm). There was a complete lack of synchronization of the abnormal development of GS, an embryo, β-hCG levels, and the duration of GS persistence in the uterine cavity after miscarriage. The following correlations occurred in the pathogenesis of EPL: chromosomal abnormalities (45% in EM and 40% in ES), history of gynecological and viral diseases (49% in EM and 41% in ES). Correlational differences in the developmental period of GS according to MSD, an embryo, the period of persistence in the uterine cavity after miscarriage, the uterine size, and mean β-hCG levels (at week 8-10) in EM were at different gestation periods before the onset of manifestation of miscarriage. Conclusion. Determination of correlation dependencies and differences in the results of monitoring diagnostic markers of different types of EPL makes it possible to develop a personalized approach to the choice of gestational sac aspiration, antibacterial, antiviral, and immunomodulatory therapy with Viferon® (interferon α-2b with antioxidant complex) for a successful consecutive pregnancy and its outcome. Key words: anembryonic pregnancy, embryonic miscarriage, correlations, pathogenesis by early pregnancy loss, early pregnancy loss, persistence of empty sac, β-hCG
Dissertations / Theses on the topic "Antiviraux – Conception"
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Note, Reine. "Conception, synthèse et évaluation d'inhibiteurs mixtes de la transcriptase inverse du VIH." Paris 5, 2000. http://www.theses.fr/2000PA05P606.
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Barral, Karine. "Conception, modélisation, synthèse et évaluation des propriétés antivirales de nouveaux analogues de nucléosides." Aix-Marseille 2, 2003. http://www.theses.fr/2003AIX22075.
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Lefebvre, Isabelle. "Essai de rationalisation dans la conception de pronucléotides à visée anti-VIH." Montpellier 2, 1994. http://www.theses.fr/1994MON20252.
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Ce present memoire illustre notre contribution au developpement d'un rationnel dans la conception de pronucleotides a visee anti-vih. Le premier chapitre resume, a partir d'etudes bibliographiques, les modes d'action et limitations des quatre analogues nucleosidiques actuellement commercialises en chimiotherapie du sida. Le second chapitre est consacre a la conception et la realisation d'un outil d'analyse par chromatographie liquide haute performance permettant l'analyse directe d'echantillons biologiques. Dans un troisieme chapitre une etude comparative entre les resultats cinetiques et mecanistiques relatifs aux etudes de decomposition et les activites antivirales in vitro de series de pronucleotides, a permis de faire evoluer la conception de nouvelles molecules susceptibles de liberer intracellulairement le nucleosides monophosphates. Des pronucleotides de l'azt comportant deux groupements enzymolabiles ont ainsi ete synthetises. Ces molecules ont presente une activite anti-vih sur des souches cellulaires devenues resistantes a l'azt
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Galeotti, Nathalie. "Conception et synthèse de mimes peptidiques analogues de substrats de la protéase du VIH." Montpellier 2, 1993. http://www.theses.fr/1993MON20002.
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L'aspartyl protease du vih a un role fondamental dans la maturation des virus et donc dans la formation de nouveaux virus infectieux. La recherche d'inhibiteurs de cette enzyme est d'un grand interet pour une lutte antivirale. Dans cette optique, ce travail est consacre a la conception et la synthese de mimes peptidiques analogues de substrats de la protease du vih. Il a ete elabore des pseudopeptides analogues de substrats de la protease dans lesquels le site d'hydrolyse a ete modifie par differents motifs. Il a ete introduit, en premier lieu, des heterocycles de types oxazolines, thiazolines et thiazoles. Cette etude s'est conclue par une mise au point d'une methode de synthese d'oxazoline et de thiazoline utilisant la reaction de mitsunobu. L'introduction du fragment amino hydroxy acide derive de la proline dans des pseudopeptides a ete aussi effectuee. L'elaboration d'un tel motif a abouti a une etude stereochimique de la reduction d'acides tetramiques. L'activite antivirale des composes synthetises est exposee dans ce travail
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Malnuit, Vincent. "Conception, synthèse et étude de nouveaux analogues de nucléosides : application dans le domaine des antiviraux et antitumoraux." Nice, 2011. http://www.theses.fr/2011NICE4001.
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Malgré des progrès importants réalisés ces dernières années, la lutte contre les infections virales et les cancers demeure un problème de santé mondiale. Ce bref bilan met en évidence la nécessité de développer de nouvelles molécules pour contourner les limites des traitements disponibles actuellement. Il est donc nécessaire de développer de nouvelles méthodes de synthèse pour accéder à ces composés afin d’évaluer leur activité biologique, et de nouveaux outils d’analyse pour étudier les interactions mises en jeu. Cette thèse, articulée autour de trois grands thèmes, s’inscrit dans ce contexte. Nous avons tout d’abord mis au point une méthode de synthèse de 1,2,3-triazolyl-nucléosides substitués en positions 4 et 5, par une réaction tandem clic/addition électrophile. Des tests biologiques ont montré la forte activité anticancéreuse de ces composés contre la LMC. Nous avons ensuite développé une stratégie de modification post-synthétique d’oligonucléotides par réaction clic. Elle permet de modifier de manière site-spécifique des oligonucléotides portant un groupement azide. Cette méthode présente plusieurs avantages et peut être utilisée pour de nombreuses applications, principalement pour le marquage spécifique des acides nucléiques. Enfin, nous avons conçu une nouvelle famille de ligands de l’ARN TAR du VIH-1 capables de se lier sélectivement à certaines structures secondaires de type tige-boucle ou tige-renflement, via l’action coopérative de plusieurs motifs de reconnaissance dont une nucléobase qui se lie spécifiquement à une paire de base UA. Parallèlement, une nouvelle méthode de criblage de triplet de bases par spectrométrie de masse est actuellement à l’étudeDespite significant progress made in recent years, the fight against viral infections and cancer remains a global health problem. This brief summary underlines the need for new compounds in order to overcome the limits of the drugs currently available. Therefore, there is a significant need to develop new methodologies for the synthesis of new bioactive molecules, and new analytical tools for the study of the involved drug/biological target interactions. To this end, the main objective of this thesis is to address these issues following the investigation of three major themes. We first developed a strategy for the synthesis of 1,2,3-triazolyl-nucleosides substituted at positions 4 and 5, using a tandem click/electrophilic addition reaction. Biological tests showed strong anticancer activity against CML for these compounds. We then developed a strategy for post-synthetic modification of oligonucleotides by click chemistry. This reaction allows post-synthetic transformation of oligonucleotides bearing an azide group in a site-specific manner. Therefore, this strategy has a great potential in various applications such as specific labelling of nucleic acids. Finally, we designed a new family of HIV-1 TAR RNA ligands that selectively bind to secondary structures such as stem-loop or stem-bulge, through a cooperative action of several recognition patterns. Among them, we used a modified nucleobase that can specifically recognize an AU base pair. Meanwhile, a new method of screening for this type of base triplets by mass spectrometry is being investigated
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Druillennec-Rodière, Sabine. "Démonstration d'une interaction directe entre la protéine de nucléocapside NCp7 et la transcriptase inverse de VIH-1 : caractérisation et inhibition. Conception de nucléo- et peptidomimétiques susceptibles d'inhiber les activités de la NCp7." Paris 5, 1999. http://www.theses.fr/1999PA05P606.
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Toulouze, Bénédicte. "Sida : revue des obstacles à la mise au point d'un vaccin anti-VIH." Bordeaux 2, 1996. http://www.theses.fr/1996BOR2P060.
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Callendret, Benoît. "Conception et évaluation de différentes approches vaccinales contre le coronavirus associé au syndrome respiratoire aigu sévère." Paris 7, 2006. http://www.theses.fr/2006PA077222.
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Le coronavirus associé au syndrome respiratoire aigu sévère (SRAS-CoV) émergea à la fin de l'année 2002 et fut responsable d'une épidémie de pneumopathie atypique chez l'homme. Nous décrivons dans ce mémoire trois approches vaccinales contre le SRAS permettant l'induction d'anticorps neutralisants contre la glycoprotéine S, qui représentent les principaux effecteurs de la réponse immune protectrice. Nous avons montré que l'expression du gène S en cellules de mammifères nécessitait des vecteurs optimisés munis d'un intron et d'éléments de régulation post-transcriptionnelle comme WPRE ou CTE. Dans le modèle souris, seule l'association d'un intron et de WPRE permet d'augmenter l'immunogénicité d'un vaccin ADN contre le SRAS de telle sorte qu'il soit efficace à une dose faible d'ADN (2 μ g). Nous avons établi des lignées cellulaires sécrétant l'ectodomaine soluble de la protéine S (Ssol). L'immunogénicité du polypeptide Ssol purifié a été étudiée dans les modèles souris et hamster. Deux injections de Ssol adjuvé par de l'Alum permettent l'induction d'une réponse immune Th2 comprenant des titres élevés d'anticorps neutralisants, et protègent les animaux contre une infection d'épreuve par le SRAS-CoV. Nous avons également montré que l'utilisation d'adjuvants développés par GlaxoSmithkline Biologicals permettait une amélioration importante des réponses induites par la protéine Ssol et l'induction d'une réponse Thl. Parallèlement, nous avons montré chez le hamster qu'une seule injection de vecteurs lentiviraux permettant l'expression de la protéine S membranaire permet l'induction d'une réponse humorale neutralisante comparable à celle induite par deux injections de la protéine SsolSevere acute respiratory syndrome associated coronavirus (SARS-CoV) emerged in late 2002 and caused an epidemic of atypic pneumonia in humans. Here, we describe three vaccine candidates designed to induce neutralizing antibodies against the viral S glycoprotein, which are the main effectors of the protective immune response. We demonstrated that efficient expression of S gene in mammalian cell lines required the use of optimized vectors containing an intron and post-transcriptional regulatory elements such as WPRE and CTE. Upon immunization of mice with low doses of naked DNA, only intron and WPRE-containing vectors were able to provide protection against challenge with SARS-CoV. We also established stable cell lines constitutively secreting a soluble form of the S protein (Ssol). The immunogenicity of purified Ssol was studied in mouse and hamster models. Two injections of the Ssol polypeptide adjuvanted with Alum induced a strong and long-lasting Th2 immune response comprising high levels of SARS-CoV-neutralizing antibodies. Upon intranasal challenge with SARS-CoV, virus replication was strongly reduced in the lungs of immunized animals and hamsters were protected from the occurrence of lesions in the respiratory tract. Moreover, the use of two new adjuvants developed by GlaxoSmithKline Biologicals further increased the anti-S humoral response and the Thl component of the immune response. Concurrently, we developed HIV-based lentiviral vectors expressing the full-length S protein as an alternate SARS vaccine candidate. In the hamster model, a single injection of these vectors induced a neutralizing antibody response similar to that induced by two injections of Ssol
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Abuduaini, Tuniyazi. "Génération de nouveaux acyclonucléosides phosphonates oléfiniques et 1-C-arylglycosides." Electronic Thesis or Diss., Orléans, 2021. http://www.theses.fr/2021ORLE3200.
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Les nucléosides et leurs analogues constituent la principale famille d’antiviraux et anticancéreux. Ils sont un outil extrêmement puissant dans la lutte efficace contre les infections virales liées à de nombreux virus tels que le HIV, le HBV, le HCV, le CMV, le VZV ainsi que le HSV; ils sont depuis plus d'un demi-siècle au centre des thérapies antivirales avec une quarantaine de composés approuvés par la FDA. Les infections virales représentent toujours un large problème de santé publique en raison de l'émergence de nouveaux virus, l'apparition de résistances aux antiviraux actuels et des phénomènes de mutations virales. Ainsi, la conception et la synthèse de nouveaux antiviraux restent toujours d'actualité. Dans la première partie ce manuscrit, dans le but de développer des nouveaux antiviraux plus actifs et sûrs, nous avons conçu et synthétisé deux nouvelles familles d’acyclonucléosides phosphonates oléfiniques sous forme prodrogues en modifiant la nucléobase, la chaîne acyclique et le groupement biolabiles. Pour ce faire, nous avons utilisé la réaction de métathèse croisée comme étape clé. Dans la deuxième partie, le champ d’application du couplage croisé de Migita-Kosugi-Stille a été exploré en utilisant des iminoalditols stannylés et une petite librairie de chlorure d'aroyles diversement substitués. De manière intéressante, le processus de formation de la liaison C‒C est stéréorétentif. Des nouveaux analogues de la N‒acétylglucosamine C‒glycosylée ont ensuite été préparés par une séquence réactionnelle de réduction, déprotection, mésylation et cyclisationNucleosides and their analogues constitute the main family of antivirals and anticancer drugs. They provide an extremely powerful tool in effectively combating viral infections associated with many viruses such as HIV, HBV, HCV, CMV, VZV and HSV; they have been at the center of antiviral therapy for more than half a century with around 40 compounds approved by the FDA. Viral infections still represent a large public health problem due to the emergence of new viruses, the appearance of resistance to current antivirals and phenomena of viral mutations. This is why the design and synthesis of new antivirals are still relevant today. In the first part of this manuscript, in order to develop new, more active and safe antivirals, we firstly designed and synthesized two new families of olefinic acyclonucleosides phosphonates under prodrug form by modifying the nucleobase, the acyclic chain and the biolabile group. To do this, we used the cross-metathesis reaction as the key step. In the second part, the "scope" of Migita-Kosugi-Stille cross couplings was explored using stannylated iminoalditols and a small library of variously substituted aroyl chloride. More interestingly, the process of formation of the C‒C bond is stereoretentive. New analogs of C‒glycosylated N‒acetylglucosamine were then prepared by a reaction sequence of reduction, deprotection, mesylation and cyclization
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Phelip, Capucine. "Conception, caractérisation et évaluation in vivo d'un vaccin nanoparticulaire anti-VIH et optimisation de sa biodisponibilité par un hydrogel thermosensible." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1280.
Full textAbstract:
Les connaissances actuelles indiquent la nécessité d’induire une réponse immunitaire à large spectre et notamment des anticorps multifonctionnels pour protéger de l’infection par le VIH. Les approches vaccinales traditionnelles n’étant pas capables d’induire d’anticorps neutralisants à large spectre (bNAbs) suffisamment puissants contre le VIH-1, des stratégies alternatives sont étudiées afin d’induire ces bnAbs. Les avancées majeures concernent le développement de (i) glycoprotéines d’enveloppe optimisées comme immunogène, (ii) vecteurs transportant et présentant l’immunogène de manière efficace et (iii) la forme galénique permettant d’augmenter la durabilité de la réponse protectrice. Dans ce contexte, l’objectif de ce doctorat est d’évaluer les réponses immunitaires induites par des nanoparticules biodégradables fonctionnalisées avec des glycoprotéines d’enveloppe du VIH et d’optimiser la libération prolongée in vivo de l’immunogène. Dans un premier temps, nous avons comparé plusieurs glycoprotéines et sélectionné une glycoprotéine d’isolat primaire optimisée (SOSIP BG505) pour ses capacités à s’adsorber de manière stable à la surface des nanoparticules biodégradables, tout en exposant les épitopes de neutralisation, et capable d’induire in vivo une réponse immunitaire systémique. Nous avons ensuite conçu un hydrogel thermosensible à base de poloxamers capable d’incorporer ces nanoparticules tout en gardant leur stabilité colloïdale et analysé leur biodistribution par imagerie corps entier chez la souris. L’injection par voie sous cutanée de cet hydrogel permet d’induire une réponse immunitaire humorale forte, stable et des IgGs de forte affinité. Cette nouvelle formulation, innovante et simple à mettre en place, apparait comme une nouvelle stratégie de vaccination applicable à de nombreuses pathologies virales nécessitant l’induction d’anticorps neutralisant de forte affinité et à large spectreCurrent knowledge indicates the need to induce a broad-spectrum immune response including multifunctional antibodies to protect against HIV infection. As traditional vaccine approaches are not capable of inducing potent broad-spectrum neutralizing antibodies (bNAbs) against HIV-1, alternative strategies are being investigated to induce these bnAbs. Major advances include the development of (i) optimized envelope glycoproteins as immunogens, (ii) efficiently carrying and immunogenic carriers, and (iii) the dosage form that would increase the durability of the protective response. In this context, the objective of this PhD is to evaluate the immune responses induced by biodegradable nanoparticles functionalized with HIV envelope glycoproteins and to optimize the in vivo sustained release of the immunogen.First, we compared several glycoproteins and selected an optimized primary isolate glycoprotein (SOSIP BG505) for its ability to be adsorbed to the surface of biodegradable nanoparticles, while exposing neutralization epitopes, and capable of inducing a systemic immune response in vivo. We then designed a thermosensitive, poloxamers-based hydrogel, capable of incorporating these nanoparticles while maintaining their colloidal stability and we have analyzed their biodistribution by whole-body imaging in mice. The subcutaneous injection of this hydrogel makes it possible to induce a strong, stable humoral immune response with high affinity IgGs. This new formulation, innovative and easy to implement, appears as a new vaccination strategy applicable to many viral diseases requiring the induction of high affinity neutralizing antibodies and broad spectrum