Direct inhibitory effect on viral entry of influenza A and SARS-CoV-2 viruses by azithromycin.
Direct inhibitory effect on viral entry of influenza A and SARS-CoV-2 viruses by azithromycin.
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阿奇霉素对甲型流感和 SARS-CoV-2 病毒进入病毒的直接抑制作用
DOI：
10.1111/cpr.12953
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发表时间：
2021-01
影响因子：
8.5
通讯作者：
Qin FX
中科院分区：
文献类型：
--
作者：
Du X;Zuo X;Meng F;Han C;Ouyang W;Han Y;Gu Y;Zhao X;Xu F;Qin FX
使用药物再利用策略，可以快速筛选出针对甲型流感病毒（IAV）和新出现的SARS冠状病毒2（SARS-CoV-2，也称为2019-nCoV）的抗病毒药物。使用先前报道的携带荧光素酶报告基因（IAV‐luc）和多种假型IAV和SARS‐CoV‐2病毒的工程化可复制PR 8毒株。为了具体评估含有IAV的囊泡的pH变化，我们构建了具有pHluorin 2的内体和溶酶体表达的A549细胞系。在这里，我们确定了阿奇霉素（AZ）作为一种有效的抑制剂对多种IAV和SARS-CoV-2菌株。我们发现AZ处理可以有效地抑制体外IAV感染。此外，使用假型病毒模型，AZ还可以显著阻断SARS-CoV-2进入HEK 293 T-ACE 2和Caco 2细胞。机制研究进一步揭示了这种作用不依赖于干扰素信号传导。AZ处理既不损害IAV病毒粒子的结合和内化，也不损害病毒复制，而是抑制病毒和空泡膜之间的融合。使用NPC 1-pHluorin 2报告细胞系，我们证实AZ处理可以碱化含有IAV病毒粒子的囊泡，从而阻止pH依赖性膜融合。总体而言，我们的研究结果表明AZ对IAV和SARS-CoV-2具有广谱抗病毒作用，可以作为潜在的临床抗SARS-CoV-2药物用于紧急情况，以及有希望的下一代抗IAV药物开发的先导化合物。阿奇霉素抑制多种IAV亚型和具有刺突突变的SARS-CoV-2假病毒的感染。阿奇霉素既不损害IAV病毒粒子的结合和内化，也不损害病毒复制，而是抑制膜融合。使用NPC 1-pHluorin 2报告细胞系，我们证实阿奇霉素处理使含有IAV病毒粒子的囊泡碱化，从而阻止pH依赖性膜融合。
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. 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. 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. 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. Azithromycin inhibits infection of multiple IAV subtypes and SARS‐CoV‐2 pseudovirus with spike mutations. Azithromycin neither impairs the binding and internalization of IAV virions, nor the viral replication, but rather inhibits the membrane fusion. Using the NPC1‐pHluorin2 reporter cell line, we confirmed that azithromycin treatment alkalizes the vesicles containing IAV virions, thereby preventing pH‐dependent membrane fusion.
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DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
通讯作者：
Choe H
影响因子：
5.5
作者：
Lou Xinhan;Matsushita, Masafumi;Kanazawa, Hiroshi
通讯作者：
Kanazawa, Hiroshi
细胞显微镜和基于荧光的细胞内细胞器中的腔pH测量。
影响因子：
5.5
作者：
Ma L;Ouyang Q;Werthmann GC;Thompson HM;Morrow EM
通讯作者：
Morrow EM
影响因子：
4.6
作者：
Menzel M;Akbarshahi H;Bjermer L;Uller L
通讯作者：
Uller L
影响因子：
3.8
作者：
Andreani, Julien;Le Bideau, Marion;Raoult, Didier
通讯作者：
Raoult, Didier