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10.1038/s41586-020-2577-1 http://scihub22266oqcxt.onion/10.1038/s41586-020-2577-1 32707573!7603405!32707573     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32707573&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2020 ; 586 (7827): 113-119 Nephropedia Template TP {{tp|p=32707573|t=2020. Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing |pdf=|usr=}}{{32707573}} gab.com Text Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=32707573 #FOAvip 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 apilimod(2-4) 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 pluripotent stem cells, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19. Twit Text FOAVip Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=32707573 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32707573 #FOAvip English Wikipedia <ref>{{Cite pmid|32707573}}</ref> Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing #MMPMID32707573 Riva L; Yuan S; Yin X; Martin-Sancho L; Matsunaga N; Pache L; Burgstaller-Muehlbacher S; De Jesus PD; Teriete P; Hull MV; Chang MW; Chan JF; Cao J; Poon VK; Herbert KM; Cheng K; Nguyen TH; Rubanov A; Pu Y; Nguyen C; Choi A; Rathnasinghe R; Schotsaert M; Miorin L; Dejosez M; Zwaka TP; Sit KY; Martinez-Sobrido L; Liu WC; White KM; Chapman ME; Lendy EK; Glynne RJ; Albrecht R; Ruppin E; Mesecar AD; Johnson JR; Benner C; Sun R; Schultz PG; Su AI; Garcia-Sastre A; Chatterjee AK; Yuen KY; Chanda SK Nature 2020[Oct]; 586 (7827): 113-119 PMID32707573show ga 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 apilimod(2-4) 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 pluripotent stem cells, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19. |*Drug Evaluation, Preclinical[MESH] |*Drug Repositioning[MESH] |Adenosine Monophosphate/analogs & derivatives/pharmacology[MESH] |Alanine/analogs & derivatives/pharmacology[MESH] |Alveolar Epithelial Cells/cytology/drug effects[MESH] |Antiviral Agents/*analysis/*pharmacology[MESH] |Betacoronavirus/*drug effects/growth & development[MESH] |COVID-19[MESH] |COVID-19 Drug Treatment[MESH] |Cell Line[MESH] |Coronavirus Infections/*drug therapy/*virology[MESH] |Cysteine Proteinase Inhibitors/analysis/pharmacology[MESH] |Dose-Response Relationship, Drug[MESH] |Drug Synergism[MESH] |Gene Expression Regulation/drug effects[MESH] |Humans[MESH] |Hydrazones[MESH] |Induced Pluripotent Stem Cells/cytology[MESH] |Models, Biological[MESH] |Morpholines/analysis/pharmacology[MESH] |Pandemics[MESH] |Pneumonia, Viral/*drug therapy/*virology[MESH] |Pyrimidines[MESH] |Reproducibility of Results[MESH] |SARS-CoV-2[MESH] |Small Molecule Libraries/analysis/pharmacology[MESH] |Triazines/analysis/pharmacology[MESH] |Virus Internalization/drug effects[MESH]Discovery of SARS-CoV-2 antiviral drugs through large-scale compound r(epmc).pdf DeepDyve Pubget Overpricing