Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.
Identifieur interne : 000662 ( Main/Corpus ); précédent : 000661; suivant : 000663Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.
Auteurs : Xia Xiao ; Conghui Wang ; De Chang ; Ying Wang ; Xiaojing Dong ; Tao Jiao ; Zhendong Zhao ; Lili Ren ; Charles S. Dela Cruz ; Lokesh Sharma ; Xiaobo Lei ; Jianwei WangSource :
- Frontiers in immunology [ 1664-3224 ] ; 2020.
English descriptors
- KwdEn :
- Animals (MeSH), Antiviral Agents (therapeutic use), COVID-19 (drug therapy), COVID-19 (epidemiology), COVID-19 (virology), Cell Line (MeSH), Drug Repositioning (methods), Fendiline (therapeutic use), HEK293 Cells (MeSH), High-Throughput Screening Assays (methods), Humans (MeSH), Monensin (therapeutic use), Pandemics (prevention & control), SARS-CoV-2 (drug effects), SARS-CoV-2 (physiology), Salicylanilides (therapeutic use), Sertraline (therapeutic use), Vortioxetine (therapeutic use).
- MESH :
- chemical , therapeutic use : Antiviral Agents, Fendiline, Monensin, Salicylanilides, Sertraline, Vortioxetine.
- drug effects : SARS-CoV-2.
- drug therapy : COVID-19.
- epidemiology : COVID-19.
- methods : Drug Repositioning, High-Throughput Screening Assays.
- physiology : SARS-CoV-2.
- prevention & control : Pandemics.
- virology : COVID-19.
- Animals, Cell Line, HEK293 Cells, Humans.
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.
DOI: 10.3389/fimmu.2020.586572
PubMed: 33324406
PubMed Central: PMC7723961
Links to Exploration step
pubmed:33324406Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.</title><author><name sortKey="Xiao, Xia" sort="Xiao, Xia" uniqKey="Xiao X" first="Xia" last="Xiao">Xia Xiao</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Conghui" sort="Wang, Conghui" uniqKey="Wang C" first="Conghui" last="Wang">Conghui Wang</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, De" sort="Chang, De" uniqKey="Chang D" first="De" last="Chang">De Chang</name><affiliation><nlm:affiliation>The Department of Pulmonary and Critical Care Medicine, Third Medical Center of Chinese PLA General Hospital, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Dong, Xiaojing" sort="Dong, Xiaojing" uniqKey="Dong X" first="Xiaojing" last="Dong">Xiaojing Dong</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Jiao, Tao" sort="Jiao, Tao" uniqKey="Jiao T" first="Tao" last="Jiao">Tao Jiao</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhao, Zhendong" sort="Zhao, Zhendong" uniqKey="Zhao Z" first="Zhendong" last="Zhao">Zhendong Zhao</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Lili" sort="Ren, Lili" uniqKey="Ren L" first="Lili" last="Ren">Lili Ren</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Dela Cruz, Charles S" sort="Dela Cruz, Charles S" uniqKey="Dela Cruz C" first="Charles S" last="Dela Cruz">Charles S. Dela Cruz</name><affiliation><nlm:affiliation>Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Sharma, Lokesh" sort="Sharma, Lokesh" uniqKey="Sharma L" first="Lokesh" last="Sharma">Lokesh Sharma</name><affiliation><nlm:affiliation>Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Lei, Xiaobo" sort="Lei, Xiaobo" uniqKey="Lei X" first="Xiaobo" last="Lei">Xiaobo Lei</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33324406</idno><idno type="pmid">33324406</idno><idno type="doi">10.3389/fimmu.2020.586572</idno><idno type="pmc">PMC7723961</idno><idno type="wicri:Area/Main/Corpus">000662</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000662</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.</title><author><name sortKey="Xiao, Xia" sort="Xiao, Xia" uniqKey="Xiao X" first="Xia" last="Xiao">Xia Xiao</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Conghui" sort="Wang, Conghui" uniqKey="Wang C" first="Conghui" last="Wang">Conghui Wang</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, De" sort="Chang, De" uniqKey="Chang D" first="De" last="Chang">De Chang</name><affiliation><nlm:affiliation>The Department of Pulmonary and Critical Care Medicine, Third Medical Center of Chinese PLA General Hospital, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Dong, Xiaojing" sort="Dong, Xiaojing" uniqKey="Dong X" first="Xiaojing" last="Dong">Xiaojing Dong</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Jiao, Tao" sort="Jiao, Tao" uniqKey="Jiao T" first="Tao" last="Jiao">Tao Jiao</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhao, Zhendong" sort="Zhao, Zhendong" uniqKey="Zhao Z" first="Zhendong" last="Zhao">Zhendong Zhao</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Lili" sort="Ren, Lili" uniqKey="Ren L" first="Lili" last="Ren">Lili Ren</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Dela Cruz, Charles S" sort="Dela Cruz, Charles S" uniqKey="Dela Cruz C" first="Charles S" last="Dela Cruz">Charles S. Dela Cruz</name><affiliation><nlm:affiliation>Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Sharma, Lokesh" sort="Sharma, Lokesh" uniqKey="Sharma L" first="Lokesh" last="Sharma">Lokesh Sharma</name><affiliation><nlm:affiliation>Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Lei, Xiaobo" sort="Lei, Xiaobo" uniqKey="Lei X" first="Xiaobo" last="Lei">Xiaobo Lei</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name><affiliation><nlm:affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Frontiers in immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Antiviral Agents (therapeutic use)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (epidemiology)</term><term>COVID-19 (virology)</term><term>Cell Line (MeSH)</term><term>Drug Repositioning (methods)</term><term>Fendiline (therapeutic use)</term><term>HEK293 Cells (MeSH)</term><term>High-Throughput Screening Assays (methods)</term><term>Humans (MeSH)</term><term>Monensin (therapeutic use)</term><term>Pandemics (prevention & control)</term><term>SARS-CoV-2 (drug effects)</term><term>SARS-CoV-2 (physiology)</term><term>Salicylanilides (therapeutic use)</term><term>Sertraline (therapeutic use)</term><term>Vortioxetine (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Fendiline</term><term>Monensin</term><term>Salicylanilides</term><term>Sertraline</term><term>Vortioxetine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Repositioning</term><term>High-Throughput Screening Assays</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Pandemics</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>HEK293 Cells</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33324406</PMID><DateCompleted><Year>2020</Year><Month>12</Month><Day>28</Day></DateCompleted><DateRevised><Year>2020</Year><Month>12</Month><Day>28</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1664-3224</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Frontiers in immunology</Title><ISOAbbreviation>Front Immunol</ISOAbbreviation></Journal><ArticleTitle>Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.</ArticleTitle><Pagination><MedlinePgn>586572</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fimmu.2020.586572</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright © 2020 Xiao, Wang, Chang, Wang, Dong, Jiao, Zhao, Ren, Dela Cruz, Sharma, Lei and Wang.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xiao</LastName><ForeName>Xia</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Conghui</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>De</ForeName><AffiliationInfo><Affiliation>The Department of Pulmonary and Critical Care Medicine, Third Medical Center of Chinese PLA General Hospital, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Xiaojing</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiao</LastName><ForeName>Tao</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Zhendong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Lili</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dela Cruz</LastName><ForeName>Charles S</ForeName><Initials>CS</Initials><AffiliationInfo><Affiliation>Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sharma</LastName><ForeName>Lokesh</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lei</LastName><ForeName>Xiaobo</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>NHC Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Respiratory Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>11</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Immunol</MedlineTA><NlmUniqueID>101560960</NlmUniqueID><ISSNLinking>1664-3224</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058492" MajorTopicYN="N">Drug Repositioning</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005275" MajorTopicYN="N">Fendiline</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057166" MajorTopicYN="N">High-Throughput Screening 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use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020280" MajorTopicYN="N">Sertraline</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000078784" MajorTopicYN="N">Vortioxetine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">COVID-19</Keyword><Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword><Keyword MajorTopicYN="Y">US Food and Drug Administration-approved compounds</Keyword><Keyword MajorTopicYN="Y">antiviral</Keyword><Keyword MajorTopicYN="Y">therapy</Keyword></KeywordList><CoiStatement>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate 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