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Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.
Xiao, Xia; Wang, Conghui; Chang, De; Wang, Ying; Dong, Xiaojing; Jiao, Tao; Zhao, Zhendong; Ren, Lili; Dela Cruz, Charles S; Sharma, Lokesh; Lei, Xiaobo; Wang, Jianwei.
  • Xiao X; NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Wang C; Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.
  • Chang; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Wang Y; NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Dong X; Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.
  • Jiao T; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Zhao Z; The Department of Pulmonary and Critical Care Medicine, Third Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Ren L; NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Dela Cruz CS; Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.
  • Sharma L; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Lei X; NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Wang J; Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.
Front Immunol ; 11: 586572, 2020.
Article in English | MEDLINE | ID: covidwho-979019
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ABSTRACT
COVID-19 pandemic has infected millions of people with mortality exceeding >1 million. There is an urgent need to find therapeutic agents that can help clear the virus to prevent severe disease and death. Identifying effective and safer drugs can provide more options to treat COVID-19 infections either alone or in combination. Here, we performed a high throughput screening of approximately 1,700 US FDA-approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 20 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine besylate, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, mefloquine, and thioridazine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating a wide therapeutic window compared to hydroxychloroquine which had a safety index of 22 in similar experiments. Mechanistically, five of the effective compounds (fendiline HCl, monensin sodium salt, vortioxetine, sertraline HCl, and salifungin) were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA-approved compounds can provide much needed therapeutic options that we urgently need during the midst of the pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / High-Throughput Screening Assays / Pandemics / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Observational study Limits: Animals / Humans Language: English Journal: Front Immunol Year: 2020 Document Type: Article Affiliation country: Fimmu.2020.586572

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / High-Throughput Screening Assays / Pandemics / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Observational study Limits: Animals / Humans Language: English Journal: Front Immunol Year: 2020 Document Type: Article Affiliation country: Fimmu.2020.586572