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Article: Alisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19

TitleAlisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19
Authors
KeywordsACE2
Alisol B 23-acetate
Anti-coronavirus
Anti-immunoinflammatory activity
COVID-19
Issue Date4-Oct-2023
PublisherElsevier
Citation
Journal of Advanced Research, 2023 How to Cite?
Abstract

Introduction: Emerging severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 causes a global health disaster and pandemic. Seeking effective anti-pan-CoVs drugs benefit critical illness patients of coronavirus disease 2019 (COVID-19) but also may play a role in emerging CoVs of the future. Objectives: This study tested the hypothesis that alisol B 23-acetate could be a viral entry inhibitor and would have proinflammatory inhibition for COVID-19 treatment. Methods: SARS-CoV-2 and its variants infected several cell lines were applied to evaluate the anti-CoVs activities of alisol B 23-aceate in vitro. The effects of alisol B 23-acetate on in vivo models were assessed by using SARS-CoV-2 and its variants challenged hamster and human angiotensin-converting enzyme 2 (ACE2) transgenic mice. The target of alisol B 23-acetate to ACE2 was analyzed using hydrogen/deuterium exchange (HDX) mass spectrometry (MS). Results: Alisol B 23-acetate had inhibitory effects on different species of coronavirus. By using HDX-MS, we found that alisol B 23-acetate had inhibition potency toward ACE2. In vivo experiments showed that alisol B 23-acetate treatment remarkably decreased viral copy, reduced CD4+ T lymphocytes and CD11b+ macrophages infiltration and ameliorated lung damages in the hamster model. In Omicron variant infected human ACE2 transgenic mice, alisol B 23-acetate effectively alleviated viral load in nasal turbinate and reduced proinflammatory cytokines interleukin 17 (IL17) and interferon γ (IFNγ) in peripheral blood. The prophylactic treatment of alisol B 23-acetate by intranasal administration significantly attenuated Omicron viral load in the hamster lung tissues. Moreover, alisol B 23-acetate treatment remarkably inhibited proinflammatory responses through mitigating the secretions of IFNγ and IL17 in the cultured human and mice lymphocytes in vitro. Conclusion: Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities.


Persistent Identifierhttp://hdl.handle.net/10722/340597
ISSN
2023 Impact Factor: 11.4
2023 SCImago Journal Rankings: 1.905

 

DC FieldValueLanguage
dc.contributor.authorDu, Qiaohui-
dc.contributor.authorLiang, Ronghui-
dc.contributor.authorWu, Meiling-
dc.contributor.authorYang, Minxiao-
dc.contributor.authorXie, Yubin-
dc.contributor.authorLiu, Qing-
dc.contributor.authorTang, Kaiming-
dc.contributor.authorLin, Xiang-
dc.contributor.authorYuan, Shuofeng-
dc.contributor.authorShen, Jiangang-
dc.date.accessioned2024-03-11T10:45:46Z-
dc.date.available2024-03-11T10:45:46Z-
dc.date.issued2023-10-04-
dc.identifier.citationJournal of Advanced Research, 2023-
dc.identifier.issn2090-1232-
dc.identifier.urihttp://hdl.handle.net/10722/340597-
dc.description.abstract<p> <span>Introduction: Emerging severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 causes a global health disaster and pandemic. Seeking effective anti-pan-CoVs drugs benefit critical illness patients of coronavirus disease 2019 (COVID-19) but also may play a role in emerging CoVs of the future. Objectives: This study tested the hypothesis that alisol B 23-acetate could be a viral entry inhibitor and would have proinflammatory inhibition for COVID-19 treatment. Methods: SARS-CoV-2 and its variants infected several cell lines were applied to evaluate the anti-CoVs activities of alisol B 23-aceate in vitro. The effects of alisol B 23-acetate on in vivo models were assessed by using SARS-CoV-2 and its variants challenged hamster and human angiotensin-converting enzyme 2 (ACE2) transgenic mice. The target of alisol B 23-acetate to ACE2 was analyzed using hydrogen/deuterium exchange (HDX) mass spectrometry (MS). Results: Alisol B 23-acetate had inhibitory effects on different species of coronavirus. By using HDX-MS, we found that alisol B 23-acetate had inhibition potency toward ACE2. In vivo experiments showed that alisol B 23-acetate treatment remarkably decreased viral copy, reduced CD4</span><sup>+</sup><span> T lymphocytes and CD11b</span><sup>+</sup><span> macrophages infiltration and ameliorated lung damages in the hamster model. In Omicron variant infected human ACE2 transgenic mice, alisol B 23-acetate effectively alleviated viral load in nasal turbinate and reduced proinflammatory cytokines interleukin 17 (IL17) and interferon γ (IFNγ) in peripheral blood. The prophylactic treatment of alisol B 23-acetate by intranasal administration significantly attenuated Omicron viral load in the hamster lung tissues. Moreover, alisol B 23-acetate treatment remarkably inhibited proinflammatory responses through mitigating the secretions of IFNγ and IL17 in the cultured human and mice lymphocytes in vitro. Conclusion: Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities.</span> <br></p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofJournal of Advanced Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectACE2-
dc.subjectAlisol B 23-acetate-
dc.subjectAnti-coronavirus-
dc.subjectAnti-immunoinflammatory activity-
dc.subjectCOVID-19-
dc.titleAlisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.jare.2023.10.002-
dc.identifier.scopuseid_2-s2.0-85174360987-
dc.identifier.eissn2090-1224-
dc.identifier.issnl2090-1224-

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