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Repurposing carrimycin as an antiviral agent against human coronaviruses,including the currently pandemic SARS-CoV-2
Authors:Haiyan Yan  Jing Sun  Kun Wang  Huiqiang Wang  Shuo Wu  Linlin Bao  Weiqing He  Dong Wang  Airu Zhu  Tian Zhang  Rongmei Gao  Biao Dong  Jianrui Li  Lu Yang  Ming Zhong  Qi Lv  Feifei Qin  Zhen Zhuang  Xiaofang Huang  Xinyi Yang  Yuhuan Li  Yongsheng Che  Jiandong Jiang
Affiliation:1. CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Antimicrobial Agents, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;2. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China;3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050, China;4. Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China;5. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Benxi 117004, China
Abstract:COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
Keywords:Coronavirus  SARS-CoV-2  HCoV-229E  HCoV-OC43  COVID-19  Carrimycin
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