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Direct inhibitory effect on viral entry of influenza A and SARS-CoV-2 viruses by azithromycin.
Du, Xiaohong; Zuo, Xiangyang; Meng, Fang; Han, Chenfeng; Ouyang, Wei; Han, Yu; Gu, Yayun; Zhao, Xin; Xu, Feng; Qin, Frank Xiaofeng.
  • Du X; Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Zuo X; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Meng F; Institute of Clinical Medicine Research, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Science and Technology Town Hospital, Suzhou, China.
  • Han C; Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Ouyang W; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Han Y; Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Gu Y; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Zhao X; Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Xu F; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Qin FX; Department of Infectious Diseases, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Cell Prolif ; 54(1): e12953, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-991253
Semantic information from SemMedBD (by NLM)
1. azithromycin COEXISTS_WITH ACE2 gene|ACE2
Subject
azithromycin
Predicate
COEXISTS_WITH
Object
ACE2 gene|ACE2
2. Virion PART_OF influenza A virus
Subject
Virion
Predicate
PART_OF
Object
influenza A virus
3. azithromycin COEXISTS_WITH ACE2 gene|ACE2
Subject
azithromycin
Predicate
COEXISTS_WITH
Object
ACE2 gene|ACE2
4. Virion PART_OF influenza A virus
Subject
Virion
Predicate
PART_OF
Object
influenza A virus
ABSTRACT

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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Antiviral Agents / Influenza A virus / Azithromycin / Influenza, Human / Virus Internalization / SARS-CoV-2 / COVID-19 Subject: Antiviral Agents / Influenza A virus / Azithromycin / Influenza, Human / Virus Internalization / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Language: English Journal: Cell Prolif Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Antiviral Agents / Influenza A virus / Azithromycin / Influenza, Human / Virus Internalization / SARS-CoV-2 / COVID-19 Subject: Antiviral Agents / Influenza A virus / Azithromycin / Influenza, Human / Virus Internalization / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Language: English Journal: Cell Prolif Year: 2021
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