A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease
Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-...
Gespeichert in:
| Veröffentlicht in: | PloS one 2021-02, Vol.16 (2), p.e0245962-e0245962, Article 0245962 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0245962 |
|---|---|
| container_issue | 2 |
| container_start_page | e0245962 |
| container_title | PloS one |
| container_volume | 16 |
| creator | Baker, Jeremy D. Uhrich, Rikki L. Kraemer, Gerald C. Love, Jason E. Kraemer, Brian C. |
| description | Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of similar to 6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found similar to 50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 |
| doi_str_mv | 10.1371/journal.pone.0245962 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1371_journal_pone_0245962</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A650392671</galeid><doaj_id>oai_doaj_org_article_895a0ece70cf42ddbee160139b5c757c</doaj_id><sourcerecordid>A650392671</sourcerecordid><originalsourceid>FETCH-LOGICAL-c743t-642e54a734a54d3fbdb7f1a73009efea6515490356777756188f16a6c78c07933</originalsourceid><addsrcrecordid>eNqNk11v0zAUhiMEYmPwDxBYQkIg1GLHn7lBqio-Jk2atMFuLcc5aTylcWY7A_497tpNK9rFkos4x8_7-vjYpyheEzwnVJLPl34Kg-nnox9gjkvGK1E-KQ5JRcuZKDF9em98ULyI8RJjTpUQz4sDSnnJMJGHRbdATZhWKMA4hdFHN6xQtAFgQK6BIbnWQUQdjCa55CJaIpOD1y6YPiITkRs6V7vkQ0S-RakDdL44O58t_UWJ1sYNaAw-gYnwsnjWZg282n2Pil_fvv5c_pidnH4_Xi5OZlYymmaClcCZkZQZzhra1k0tW5L_Ma6gBSM44azClAuZHy6IUi0RRlipLJYVpUfF263v2Puod0WKumSKKVkqrDJxvCUaby71GNzahL_aG6dvAj6stAnJ2R60qrjBYEFi27KyaWoAIjChVc2t5NJmry-71aZ6DY3NFcuV2TPdnxlcp1f-WkvFMcv5HhUfdgbBX00Qk167aKHvzQB-usmbc0KUIBl99x_68O521MrkDbih9XlduzHVC8ExrUohN17zB6j8NrB2Nt-o1uX4nuDjniAzCf6klZli1MfnZ49nTy_22ff32A5Mn7ro-yk5P8R9kG1BG3yMAdq7IhOsNw1xWw29aQi9a4gse3P_gO5Etx2QAbUFfkPt22gdDBbuMIyxIIJLxfIIl0uXzCazpZ-GlKWfHi-l_wDiYSVD</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2484872808</pqid></control><display><type>article</type><title>A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Baker, Jeremy D. ; Uhrich, Rikki L. ; Kraemer, Gerald C. ; Love, Jason E. ; Kraemer, Brian C.</creator><contributor>Schang, Luis M.</contributor><creatorcontrib>Baker, Jeremy D. ; Uhrich, Rikki L. ; Kraemer, Gerald C. ; Love, Jason E. ; Kraemer, Brian C. ; Schang, Luis M.</creatorcontrib><description>Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of similar to 6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found similar to 50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 <= 50 mu M. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0245962</identifier><identifier>PMID: 33524017</identifier><language>eng</language><publisher>SAN FRANCISCO: Public Library Science</publisher><subject>Antiviral agents ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Biological Assay ; Biology and Life Sciences ; Clinical trials ; Computer programs ; Coronaviridae ; Coronaviruses ; COVID-19 ; Drafting software ; Drug development ; Drug dosages ; Drug Evaluation, Preclinical ; Drug Repositioning ; Drug screening ; Drug therapy ; Editing ; Education ; Fluorescence ; Genomes ; Geriatrics ; Gerontology ; Global health ; Health care ; Hepacivirus - drug effects ; Hepatitis ; Hepatitis C ; Hepatitis C - drug therapy ; Hepatitis C virus ; High-Throughput Screening Assays ; Humans ; Infections ; Medicine ; Medicine and health sciences ; Methodology ; Multidisciplinary Sciences ; Pandemics ; Pathology ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology ; Pharmacology, Experimental ; Protease inhibitors ; Protease Inhibitors - pharmacology ; Proteins ; Psychiatry ; Public health ; Reproducibility of Results ; Research and Analysis Methods ; Respiratory diseases ; Reviews ; RNA viruses ; SARS-CoV-2 - drug effects ; Science & Technology ; Science & Technology - Other Topics ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Software ; Toxicity ; Veterans ; Viral diseases ; Viruses</subject><ispartof>PloS one, 2021-02, Vol.16 (2), p.e0245962-e0245962, Article 0245962</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>40</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000616578400002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c743t-642e54a734a54d3fbdb7f1a73009efea6515490356777756188f16a6c78c07933</citedby><cites>FETCH-LOGICAL-c743t-642e54a734a54d3fbdb7f1a73009efea6515490356777756188f16a6c78c07933</cites><orcidid>0000-0002-2252-7634</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850479/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850479/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,2929,23871,27929,27930,39263,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33524017$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Schang, Luis M.</contributor><creatorcontrib>Baker, Jeremy D.</creatorcontrib><creatorcontrib>Uhrich, Rikki L.</creatorcontrib><creatorcontrib>Kraemer, Gerald C.</creatorcontrib><creatorcontrib>Love, Jason E.</creatorcontrib><creatorcontrib>Kraemer, Brian C.</creatorcontrib><title>A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease</title><title>PloS one</title><addtitle>PLOS ONE</addtitle><addtitle>PLoS One</addtitle><description>Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of similar to 6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found similar to 50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 <= 50 mu M. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.</description><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Biological Assay</subject><subject>Biology and Life Sciences</subject><subject>Clinical trials</subject><subject>Computer programs</subject><subject>Coronaviridae</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Drafting software</subject><subject>Drug development</subject><subject>Drug dosages</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Repositioning</subject><subject>Drug screening</subject><subject>Drug therapy</subject><subject>Editing</subject><subject>Education</subject><subject>Fluorescence</subject><subject>Genomes</subject><subject>Geriatrics</subject><subject>Gerontology</subject><subject>Global health</subject><subject>Health care</subject><subject>Hepacivirus - drug effects</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C - drug therapy</subject><subject>Hepatitis C virus</subject><subject>High-Throughput Screening Assays</subject><subject>Humans</subject><subject>Infections</subject><subject>Medicine</subject><subject>Medicine and health sciences</subject><subject>Methodology</subject><subject>Multidisciplinary Sciences</subject><subject>Pandemics</subject><subject>Pathology</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Pharmacology, Experimental</subject><subject>Protease inhibitors</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Proteins</subject><subject>Psychiatry</subject><subject>Public health</subject><subject>Reproducibility of Results</subject><subject>Research and Analysis Methods</subject><subject>Respiratory diseases</subject><subject>Reviews</subject><subject>RNA viruses</subject><subject>SARS-CoV-2 - drug effects</subject><subject>Science & Technology</subject><subject>Science & Technology - Other Topics</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Software</subject><subject>Toxicity</subject><subject>Veterans</subject><subject>Viral diseases</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQkIg1GLHn7lBqio-Jk2atMFuLcc5aTylcWY7A_497tpNK9rFkos4x8_7-vjYpyheEzwnVJLPl34Kg-nnox9gjkvGK1E-KQ5JRcuZKDF9em98ULyI8RJjTpUQz4sDSnnJMJGHRbdATZhWKMA4hdFHN6xQtAFgQK6BIbnWQUQdjCa55CJaIpOD1y6YPiITkRs6V7vkQ0S-RakDdL44O58t_UWJ1sYNaAw-gYnwsnjWZg282n2Pil_fvv5c_pidnH4_Xi5OZlYymmaClcCZkZQZzhra1k0tW5L_Ma6gBSM44azClAuZHy6IUi0RRlipLJYVpUfF263v2Puod0WKumSKKVkqrDJxvCUaby71GNzahL_aG6dvAj6stAnJ2R60qrjBYEFi27KyaWoAIjChVc2t5NJmry-71aZ6DY3NFcuV2TPdnxlcp1f-WkvFMcv5HhUfdgbBX00Qk167aKHvzQB-usmbc0KUIBl99x_68O521MrkDbih9XlduzHVC8ExrUohN17zB6j8NrB2Nt-o1uX4nuDjniAzCf6klZli1MfnZ49nTy_22ff32A5Mn7ro-yk5P8R9kG1BG3yMAdq7IhOsNw1xWw29aQi9a4gse3P_gO5Etx2QAbUFfkPt22gdDBbuMIyxIIJLxfIIl0uXzCazpZ-GlKWfHi-l_wDiYSVD</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Baker, Jeremy D.</creator><creator>Uhrich, Rikki L.</creator><creator>Kraemer, Gerald C.</creator><creator>Love, Jason E.</creator><creator>Kraemer, Brian C.</creator><general>Public Library Science</general><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2252-7634</orcidid></search><sort><creationdate>20210201</creationdate><title>A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease</title><author>Baker, Jeremy D. ; Uhrich, Rikki L. ; Kraemer, Gerald C. ; Love, Jason E. ; Kraemer, Brian C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c743t-642e54a734a54d3fbdb7f1a73009efea6515490356777756188f16a6c78c07933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Biological Assay</topic><topic>Biology and Life Sciences</topic><topic>Clinical trials</topic><topic>Computer programs</topic><topic>Coronaviridae</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Drafting software</topic><topic>Drug development</topic><topic>Drug dosages</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Repositioning</topic><topic>Drug screening</topic><topic>Drug therapy</topic><topic>Editing</topic><topic>Education</topic><topic>Fluorescence</topic><topic>Genomes</topic><topic>Geriatrics</topic><topic>Gerontology</topic><topic>Global health</topic><topic>Health care</topic><topic>Hepacivirus - drug effects</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C - drug therapy</topic><topic>Hepatitis C virus</topic><topic>High-Throughput Screening Assays</topic><topic>Humans</topic><topic>Infections</topic><topic>Medicine</topic><topic>Medicine and health sciences</topic><topic>Methodology</topic><topic>Multidisciplinary Sciences</topic><topic>Pandemics</topic><topic>Pathology</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Pharmacology, Experimental</topic><topic>Protease inhibitors</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Proteins</topic><topic>Psychiatry</topic><topic>Public health</topic><topic>Reproducibility of Results</topic><topic>Research and Analysis Methods</topic><topic>Respiratory diseases</topic><topic>Reviews</topic><topic>RNA viruses</topic><topic>SARS-CoV-2 - drug effects</topic><topic>Science & Technology</topic><topic>Science & Technology - Other Topics</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Software</topic><topic>Toxicity</topic><topic>Veterans</topic><topic>Viral diseases</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baker, Jeremy D.</creatorcontrib><creatorcontrib>Uhrich, Rikki L.</creatorcontrib><creatorcontrib>Kraemer, Gerald C.</creatorcontrib><creatorcontrib>Love, Jason E.</creatorcontrib><creatorcontrib>Kraemer, Brian C.</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baker, Jeremy D.</au><au>Uhrich, Rikki L.</au><au>Kraemer, Gerald C.</au><au>Love, Jason E.</au><au>Kraemer, Brian C.</au><au>Schang, Luis M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease</atitle><jtitle>PloS one</jtitle><stitle>PLOS ONE</stitle><addtitle>PLoS One</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>16</volume><issue>2</issue><spage>e0245962</spage><epage>e0245962</epage><pages>e0245962-e0245962</pages><artnum>0245962</artnum><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Effective SARS-CoV-2 antiviral drugs are desperately needed. The SARS-CoV-2 main protease (Mpro) appears as an attractive target for drug development. We show that the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of similar to 6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro and found similar to 50 compounds with activity against Mpro. Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 <= 50 mu M. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir. This work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than boceprevir and suitable for rapid repurposing.</abstract><cop>SAN FRANCISCO</cop><pub>Public Library Science</pub><pmid>33524017</pmid><doi>10.1371/journal.pone.0245962</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-2252-7634</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-02, Vol.16 (2), p.e0245962-e0245962, Article 0245962 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_crossref_primary_10_1371_journal_pone_0245962 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Biological Assay Biology and Life Sciences Clinical trials Computer programs Coronaviridae Coronaviruses COVID-19 Drafting software Drug development Drug dosages Drug Evaluation, Preclinical Drug Repositioning Drug screening Drug therapy Editing Education Fluorescence Genomes Geriatrics Gerontology Global health Health care Hepacivirus - drug effects Hepatitis Hepatitis C Hepatitis C - drug therapy Hepatitis C virus High-Throughput Screening Assays Humans Infections Medicine Medicine and health sciences Methodology Multidisciplinary Sciences Pandemics Pathology Pharmacodynamics Pharmacokinetics Pharmacology Pharmacology, Experimental Protease inhibitors Protease Inhibitors - pharmacology Proteins Psychiatry Public health Reproducibility of Results Research and Analysis Methods Respiratory diseases Reviews RNA viruses SARS-CoV-2 - drug effects Science & Technology Science & Technology - Other Topics Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Software Toxicity Veterans Viral diseases Viruses |
| title | A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T00%3A17%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20drug%20repurposing%20screen%20identifies%20hepatitis%20C%20antivirals%20as%20inhibitors%20of%20the%20SARS-CoV2%20main%20protease&rft.jtitle=PloS%20one&rft.au=Baker,%20Jeremy%20D.&rft.date=2021-02-01&rft.volume=16&rft.issue=2&rft.spage=e0245962&rft.epage=e0245962&rft.pages=e0245962-e0245962&rft.artnum=0245962&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0245962&rft_dat=%3Cgale_cross%3EA650392671%3C/gale_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2484872808&rft_id=info:pmid/33524017&rft_galeid=A650392671&rft_doaj_id=oai_doaj_org_article_895a0ece70cf42ddbee160139b5c757c&rfr_iscdi=true |