Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing.

Nature
L. RivaSumit K Chanda

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to take at least 12-18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose-response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2-4 and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from induced pluripote...Continue Reading

References

May 1, 1991·DICP : the Annals of Pharmacotherapy·J C Garrelts
May 18, 2004·Biochemical and Biophysical Research Communications·Norio YamamotoNaoki Yamamoto
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Sep 18, 2008·Bioorganic & Medicinal Chemistry Letters·Arun K GhoshAndrew D Mesecar
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kiira RatiaAndrew D Mesecar
Feb 12, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Richard EastellSteve Deacon
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Apr 13, 2012·Genome Medicine·Yvonne Y Li, Steven Jm Jones
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 4, 2012·Expert Review of Anti-infective Therapy·Yanchen Zhou, Graham Simmons
Dec 14, 2012·PLoS Neglected Tropical Diseases·Andrea MarziHeinz Feldmann
Jul 23, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Richard EastellSteve Deacon
Oct 19, 2013·The Journal of Clinical Investigation·Mahboobe GhaediLaura E Niklason
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Apr 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael B HarbutFeng Wang
Mar 30, 2016·Current Opinion in Virology·Tomas Cihlar, Marshall Fordyce
Feb 6, 2017·PLoS Neglected Tropical Diseases·Melissa S LoveCase W McNamara
Apr 14, 2017·PLoS Neglected Tropical Diseases·Elizabeth A NelsonJudith M White
Apr 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Michael J BollongPeter G Schultz
Aug 19, 2017·The Lancet Infectious Diseases·Peter Ferenci
Oct 5, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jeff JanesArnab K Chatterjee
Jan 12, 2019·Nature Communications·Shuofeng YuanKwok-Yung Yuen
Apr 5, 2019·Nature Communications·Yingyao ZhouSumit K Chanda
Nov 7, 2019·Journal of Cellular Biochemistry·Farhath SultanaRicardo A Battaglino
Jan 16, 2020·Microorganisms·Sarah D'AlessandroSerena Delbue
Feb 13, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Kelvin Kai-Wang ToKwok-Yung Yuen
Feb 23, 2020·Journal of Korean Medical Science·Wan Beom ParkMyoung Don Oh

❮ Previous
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Citations

Sep 3, 2020·Nanomedicine·Georgia Wilson JonesBengt Fadeel
Aug 24, 2020·The American Journal of Tropical Medicine and Hygiene·Craig R RaynerEdward J Mills
Oct 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Meng WuDennis L Kasper
Oct 19, 2020·Protein Science : a Publication of the Protein Society·Rose OughtredMike Tyers
Nov 26, 2020·Proteomics·Lucia Grenga, Jean Armengaud
Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa L AugustinTaufiq Rahman
Dec 6, 2020·Medicinal Research Reviews·Jimin XuJia Zhou
Dec 8, 2020·Expert Opinion on Therapeutic Patents·Jacopo CusinatoMattia Mori
Nov 13, 2020·Emerging Microbes & Infections·Cun LiKwok Yung Yuen
Aug 14, 2020·The Journal of Cell Biology·Fred D MastJohn D Aitchison
Dec 29, 2020·Journal of Biomolecular Structure & Dynamics·Julián F Fernández, Martín J Lavecchia
Jan 6, 2021·Journal of Biomolecular Structure & Dynamics·Pushyaraga P Venugopal, Debashree Chakraborty
Jan 8, 2021·PLoS Neglected Tropical Diseases·Veronica Schmitz, Jéssica Brandão Dos Santos
Jan 8, 2021·Frontiers in Bioengineering and Biotechnology·Tobias BierigRoger M Benoit
Nov 16, 2020·International Immunopharmacology·Arun KumarVishal Aggarwal
Nov 21, 2020·The Journal of Biological Chemistry·Caroline B PlesciaRobert V Stahelin
Dec 31, 2020·STAR Protocols·Touraj Aligholipour FarzaniAlon Herschhorn
Oct 31, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Khalid El BairiSaid Afqir
Jan 22, 2021·Expert Opinion on Therapeutic Patents·Ilaria VicentiFrancesco Saladini
Dec 18, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tesia BobrowskiEugene N Muratov
Jan 20, 2021·Journal of Proteome Research·Paige HaasRuth Hüttenhain
Feb 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isabella RomeoStefano Alcaro
Dec 12, 2020·Frontiers in Plant Science·Tatiana MatveevaSofia Sokornova
Dec 22, 2020·Clinical & Translational Immunology·Marina GarcíaUNKNOWN Karolinska KI/K COVID‐19 Study Group
Jan 8, 2021·Global Health & Medicine·Robert W Shafer
Jan 23, 2021·Membranes·Jordana Muñoz-BasagoitiNuria Izquierdo-Useros
Jan 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ruixuan WangSheng-Xiang Lin
Jan 9, 2021·Frontiers in Medicine·Angela Holly VillamagnaJ Stone Doggett
Jan 15, 2021·Journal of Experimental Pharmacology·Pasquale PaglianoAmelia Filippelli
Jan 26, 2021·Journal of Parkinson's Disease·Conor Fearon, Alfonso Fasano
Oct 17, 2020·The Journal of Biological Chemistry·Daniel W KnellerAndrey Kovalevsky
Dec 22, 2020·Expert Opinion on Drug Discovery·Carolina L BelleraAlan Talevi
Dec 3, 2020·Risk Management and Healthcare Policy·Nandeeta SamadMainul Haque

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Datasets Mentioned

BETA
MT230904
GSE153940
MN908947

Methods Mentioned

BETA
RNA-seq
flow cytometry
light
PCR
size-exclusion chromatography
size-exclusion chromatographic

Software Mentioned

gene set enrichment analysis ( GSEA )
viridis
ReFRAME
pheatmap
GVK Excelra GoStar
Calibr Excelra
Metascape
R
GSEA
Clarivate

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