Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro
An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evalu...
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| Veröffentlicht in: | Antiviral research 2020-06, Vol.178, p.104786-104786, Article 104786 |
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| creator | Choy, Ka-Tim Wong, Alvina Yin-Lam Kaewpreedee, Prathanporn Sia, Sin Fun Chen, Dongdong Hui, Kenrie Pui Yan Chu, Daniel Ka Wing Chan, Michael Chi Wai Cheung, Peter Pak-Hang Huang, Xuhui Peiris, Malik Yen, Hui-Ling |
| description | An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.
•Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC50 at 23.15 μM.•Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC50 at 26.63 μM.•Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC50 at 2.55 and 0.46 μM, respectively.•Combination of remdesivir and emetine showed synergistic effect in vitro. |
| doi_str_mv | 10.1016/j.antiviral.2020.104786 |
| format | Article |
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•Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC50 at 23.15 μM.•Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC50 at 26.63 μM.•Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC50 at 2.55 and 0.46 μM, respectively.•Combination of remdesivir and emetine showed synergistic effect in vitro.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2020.104786</identifier><identifier>PMID: 32251767</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>ABSTRACT ; Adenosine Monophosphate - analogs & derivatives ; Alanine - analogs & derivatives ; Amides - pharmacology ; Animals ; Antimetabolites - pharmacology ; Antiviral Agents - pharmacology ; Betacoronavirus - drug effects ; Betacoronavirus - physiology ; Chlorocebus aethiops ; Coronavirus Infections - drug therapy ; Coronavirus Infections - virology ; COVID-19 ; Drug Combinations ; Emetine ; Emetine - pharmacology ; Epithelial Cells ; Homoharringtonine ; Homoharringtonine - pharmacology ; Humans ; Lopinavir ; Lopinavir - pharmacology ; Pandemics ; Pneumonia, Viral - drug therapy ; Pneumonia, Viral - virology ; Pyrazines - pharmacology ; Remdesivir ; Ribavirin - pharmacology ; Ritonavir ; SARS-CoV-2 ; Vero Cells ; Virus Replication - drug effects</subject><ispartof>Antiviral research, 2020-06, Vol.178, p.104786-104786, Article 104786</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><rights>2020 Elsevier B.V. All rights reserved. 2020 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-8966d1df27210022018fd033d1cd4fa54146c85c63a1f49cdece0664b32c908d3</citedby><cites>FETCH-LOGICAL-c475t-8966d1df27210022018fd033d1cd4fa54146c85c63a1f49cdece0664b32c908d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.antiviral.2020.104786$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32251767$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choy, Ka-Tim</creatorcontrib><creatorcontrib>Wong, Alvina Yin-Lam</creatorcontrib><creatorcontrib>Kaewpreedee, Prathanporn</creatorcontrib><creatorcontrib>Sia, Sin Fun</creatorcontrib><creatorcontrib>Chen, Dongdong</creatorcontrib><creatorcontrib>Hui, Kenrie Pui Yan</creatorcontrib><creatorcontrib>Chu, Daniel Ka Wing</creatorcontrib><creatorcontrib>Chan, Michael Chi Wai</creatorcontrib><creatorcontrib>Cheung, Peter Pak-Hang</creatorcontrib><creatorcontrib>Huang, Xuhui</creatorcontrib><creatorcontrib>Peiris, Malik</creatorcontrib><creatorcontrib>Yen, Hui-Ling</creatorcontrib><title>Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.
•Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC50 at 23.15 μM.•Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC50 at 26.63 μM.•Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC50 at 2.55 and 0.46 μM, respectively.•Combination of remdesivir and emetine showed synergistic effect in vitro.</description><subject>ABSTRACT</subject><subject>Adenosine Monophosphate - analogs & derivatives</subject><subject>Alanine - analogs & derivatives</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Antimetabolites - pharmacology</subject><subject>Antiviral Agents - pharmacology</subject><subject>Betacoronavirus - drug effects</subject><subject>Betacoronavirus - physiology</subject><subject>Chlorocebus aethiops</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - virology</subject><subject>COVID-19</subject><subject>Drug Combinations</subject><subject>Emetine</subject><subject>Emetine - pharmacology</subject><subject>Epithelial Cells</subject><subject>Homoharringtonine</subject><subject>Homoharringtonine - pharmacology</subject><subject>Humans</subject><subject>Lopinavir</subject><subject>Lopinavir - pharmacology</subject><subject>Pandemics</subject><subject>Pneumonia, Viral - drug therapy</subject><subject>Pneumonia, Viral - virology</subject><subject>Pyrazines - pharmacology</subject><subject>Remdesivir</subject><subject>Ribavirin - pharmacology</subject><subject>Ritonavir</subject><subject>SARS-CoV-2</subject><subject>Vero Cells</subject><subject>Virus Replication - drug effects</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkFtLwzAUx4MoOqdfQfsB1pmkbdK-CGN4A0GYlzcJWXLqzliTkcaC397O6dAnn87hnP8FfoScMzpmlImL5Vi7iB0GvRpzyjfXXJZijwxYKXla0Ursk0GvFGlW5PyIHLftklIqZFUekqOM84JJIQfkdQaNhXYTNUpWfo1Of63QQEQHo0Q7myx84xc6BHRv0bv-nKBb4Bxj8jiZPaZT_5LyJMB6hUZH9K5_Jx3G4E_IQa1XLZx-zyF5vr56mt6m9w83d9PJfWpyWcS0rISwzNZcckYp55SVtaVZZpmxea2LnOXClIURmWZ1XhkLBqgQ-TzjpqKlzYbkcpu7fp83YA242JNR64CNDh_Ka1R_Pw4X6s13SjIus1L0AXIbYIJv2wD1zsuo2hBXS7UjrjbE1ZZ47zz7Xb3z_SDuBZOtAHoAHUJQrUFwBiwGMFFZj_-WfAK405hc</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Choy, Ka-Tim</creator><creator>Wong, Alvina Yin-Lam</creator><creator>Kaewpreedee, Prathanporn</creator><creator>Sia, Sin Fun</creator><creator>Chen, Dongdong</creator><creator>Hui, Kenrie Pui Yan</creator><creator>Chu, Daniel Ka Wing</creator><creator>Chan, Michael Chi Wai</creator><creator>Cheung, Peter Pak-Hang</creator><creator>Huang, Xuhui</creator><creator>Peiris, Malik</creator><creator>Yen, Hui-Ling</creator><general>Elsevier B.V</general><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>5PM</scope></search><sort><creationdate>20200601</creationdate><title>Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro</title><author>Choy, Ka-Tim ; Wong, Alvina Yin-Lam ; Kaewpreedee, Prathanporn ; Sia, Sin Fun ; Chen, Dongdong ; Hui, Kenrie Pui Yan ; Chu, Daniel Ka Wing ; Chan, Michael Chi Wai ; Cheung, Peter Pak-Hang ; Huang, Xuhui ; Peiris, Malik ; Yen, Hui-Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-8966d1df27210022018fd033d1cd4fa54146c85c63a1f49cdece0664b32c908d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>ABSTRACT</topic><topic>Adenosine Monophosphate - analogs & derivatives</topic><topic>Alanine - analogs & derivatives</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Antimetabolites - pharmacology</topic><topic>Antiviral Agents - pharmacology</topic><topic>Betacoronavirus - drug effects</topic><topic>Betacoronavirus - physiology</topic><topic>Chlorocebus aethiops</topic><topic>Coronavirus Infections - drug therapy</topic><topic>Coronavirus Infections - virology</topic><topic>COVID-19</topic><topic>Drug Combinations</topic><topic>Emetine</topic><topic>Emetine - pharmacology</topic><topic>Epithelial Cells</topic><topic>Homoharringtonine</topic><topic>Homoharringtonine - pharmacology</topic><topic>Humans</topic><topic>Lopinavir</topic><topic>Lopinavir - pharmacology</topic><topic>Pandemics</topic><topic>Pneumonia, Viral - drug therapy</topic><topic>Pneumonia, Viral - virology</topic><topic>Pyrazines - pharmacology</topic><topic>Remdesivir</topic><topic>Ribavirin - pharmacology</topic><topic>Ritonavir</topic><topic>SARS-CoV-2</topic><topic>Vero Cells</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choy, Ka-Tim</creatorcontrib><creatorcontrib>Wong, Alvina Yin-Lam</creatorcontrib><creatorcontrib>Kaewpreedee, Prathanporn</creatorcontrib><creatorcontrib>Sia, Sin Fun</creatorcontrib><creatorcontrib>Chen, Dongdong</creatorcontrib><creatorcontrib>Hui, Kenrie Pui Yan</creatorcontrib><creatorcontrib>Chu, Daniel Ka Wing</creatorcontrib><creatorcontrib>Chan, Michael Chi Wai</creatorcontrib><creatorcontrib>Cheung, Peter Pak-Hang</creatorcontrib><creatorcontrib>Huang, Xuhui</creatorcontrib><creatorcontrib>Peiris, Malik</creatorcontrib><creatorcontrib>Yen, Hui-Ling</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choy, Ka-Tim</au><au>Wong, Alvina Yin-Lam</au><au>Kaewpreedee, Prathanporn</au><au>Sia, Sin Fun</au><au>Chen, Dongdong</au><au>Hui, Kenrie Pui Yan</au><au>Chu, Daniel Ka Wing</au><au>Chan, Michael Chi Wai</au><au>Cheung, Peter Pak-Hang</au><au>Huang, Xuhui</au><au>Peiris, Malik</au><au>Yen, Hui-Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>178</volume><spage>104786</spage><epage>104786</epage><pages>104786-104786</pages><artnum>104786</artnum><issn>0166-3542</issn><eissn>1872-9096</eissn><abstract>An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.
•Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC50 at 23.15 μM.•Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC50 at 26.63 μM.•Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC50 at 2.55 and 0.46 μM, respectively.•Combination of remdesivir and emetine showed synergistic effect in vitro.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32251767</pmid><doi>10.1016/j.antiviral.2020.104786</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Antiviral research, 2020-06, Vol.178, p.104786-104786, Article 104786 |
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| subjects | ABSTRACT Adenosine Monophosphate - analogs & derivatives Alanine - analogs & derivatives Amides - pharmacology Animals Antimetabolites - pharmacology Antiviral Agents - pharmacology Betacoronavirus - drug effects Betacoronavirus - physiology Chlorocebus aethiops Coronavirus Infections - drug therapy Coronavirus Infections - virology COVID-19 Drug Combinations Emetine Emetine - pharmacology Epithelial Cells Homoharringtonine Homoharringtonine - pharmacology Humans Lopinavir Lopinavir - pharmacology Pandemics Pneumonia, Viral - drug therapy Pneumonia, Viral - virology Pyrazines - pharmacology Remdesivir Ribavirin - pharmacology Ritonavir SARS-CoV-2 Vero Cells Virus Replication - drug effects |
| title | Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro |
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