Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8109699 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9096 (Electronic) Linking ISSN: 01663542 NLM ISO Abbreviation: Antiviral Res Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: [Amsterdam ; New York : Elsevier/North-Holland Biomedical Press, c1981-
    • Subject Terms:
      Antimetabolites/*pharmacology ; Antiviral Agents/*pharmacology ; Betacoronavirus/*drug effects ; Coronavirus Infections/*drug therapy ; Coronavirus Infections/*virology ; Emetine/*pharmacology ; Homoharringtonine/*pharmacology ; Lopinavir/*pharmacology ; Pneumonia, Viral/*drug therapy ; Pneumonia, Viral/*virology ; Virus Replication/*drug effects; Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Amides/pharmacology ; Animals ; Betacoronavirus/physiology ; COVID-19 ; Chlorocebus aethiops ; Drug Combinations ; Epithelial Cells ; Humans ; Pandemics ; Pyrazines/pharmacology ; Ribavirin/pharmacology ; SARS-CoV-2 ; Vero Cells ; COVID-19 Drug Treatment
    • 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.
      (Copyright © 2020 Elsevier B.V. All rights reserved.)
    • Comments:
      Comment in: Pharmacol Res. 2020 Aug;158:104898. (PMID: 32438034)
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    • Grant Information:
      HHSN272201400006C United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: ABSTRACT; COVID-19; Emetine; Homoharringtonine; Lopinavir; Remdesivir; Ritonavir
    • Accession Number:
      0 (Amides)
      0 (Antimetabolites)
      0 (Antiviral Agents)
      0 (Drug Combinations)
      0 (Pyrazines)
      2494G1JF75 (Lopinavir)
      3QKI37EEHE (remdesivir)
      415SHH325A (Adenosine Monophosphate)
      49717AWG6K (Ribavirin)
      6FG8041S5B (Homoharringtonine)
      EW5GL2X7E0 (favipiravir)
      OF5P57N2ZX (Alanine)
      X8D5EPO80M (Emetine)
    • Publication Date:
      Date Created: 20200407 Date Completed: 20200706 Latest Revision: 20221207
    • Publication Date:
      20240829
    • Accession Number:
      PMC7127386
    • Accession Number:
      10.1016/j.antiviral.2020.104786
    • Accession Number:
      32251767