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Front Cell Infect Microbiol ; 11: 813645, 2021.
Article in English | MEDLINE | ID: covidwho-1581376


[This corrects the article DOI: 10.3389/fcimb.2021.720357.].

Front Cell Infect Microbiol ; 11: 720357, 2021.
Article in English | MEDLINE | ID: covidwho-1497025


SARS-coronavirus 2 (SARS-CoV-2), pathogen of coronavirus disease 2019 (COVID-19), is constantly evolving to adapt to the host and evade antiviral immunity. The newly emerging variants N501Y.V1 (B.1.1.7) and N501Y.V2 (B.1.351), first reported in the United Kingdom and South Africa respectively, raised concerns due to the unusually rapid global spread. The mutations in spike (S) protein may contribute to the rapid spread of these variants. Here, with a vesicular stomatitis virus (VSV)-based pseudotype system, we demonstrated that the pseudovirus bearing N501Y.V2 S protein has higher infection efficiency than pseudovirus with wildtype (WT) and D614G S protein. Moreover, pseudovirus with N501Y.V1 or N501Y.V2 S protein has better thermal stability than WT and D614G, suggesting these mutations of variants may increase the stability of SARS-CoV-2 S protein and virion. However, the pseudovirus bearing N501Y.V1 or N501Y.V2 S protein has similar sensitivity to inhibitors of protease and endocytosis with WT and D614G. These findings could be of value in preventing the spread of virus and developing drugs for emerging SARS-CoV-2 variants.

COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Mutation , Spike Glycoprotein, Coronavirus/genetics
Cell Prolif ; 54(1): e12953, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-991253


OBJECTIVES: Using strategy of drug repurposing, antiviral agents against influenza A virus (IAV) and newly emerging SARS-coronavirus 2 (SARS-CoV-2, also as 2019-nCoV) could be quickly screened out. MATERIALS AND METHODS: A previously reported engineered replication-competent PR8 strain carrying luciferase reporter gene (IAV-luc) and multiple pseudotyped IAV and SARS-CoV-2 virus was used. To specifically evaluate the pH change of vesicles containing IAV, we constructed an A549 cell line with endosomal and lysosomal expression of pHluorin2. RESULTS: Here, we identified azithromycin (AZ) as an effective inhibitor against multiple IAV and SARS-CoV-2 strains. We found that AZ treatment could potently inhibit IAV infection in vitro. Moreover, using pseudotyped virus model, AZ could also markedly block the entry of SARS-CoV-2 in HEK293T-ACE2 and Caco2 cells. Mechanistic studies further revealed that such effect was independent of interferon signalling. AZ treatment neither impaired the binding and internalization of IAV virions, nor the viral replication, but rather inhibited the fusion between viral and vacuolar membranes. Using a NPC1-pHluorin2 reporter cell line, we confirmed that AZ treatment could alkalize the vesicles containing IAV virions, thereby preventing pH-dependent membrane fusion. CONCLUSIONS: Overall, our findings demonstrate that AZ can exert broad-spectrum antiviral effects against IAV and SARS-CoV-2, and could be served as a potential clinical anti-SARS-CoV-2 drug in emergency as well as a promising lead compound for the development of next-generation anti-IAV drugs.

Antiviral Agents/pharmacology , Azithromycin/pharmacology , COVID-19/metabolism , Influenza A virus/metabolism , Influenza, Human/metabolism , SARS-CoV-2/metabolism , Virus Internalization/drug effects , A549 Cells , COVID-19/drug therapy , COVID-19/genetics , Caco-2 Cells , HEK293 Cells , HeLa Cells , Humans , Influenza A virus/genetics , Influenza, Human/drug therapy , Influenza, Human/genetics , Interferons/genetics , Interferons/metabolism , SARS-CoV-2/genetics , Signal Transduction/drug effects , Signal Transduction/genetics