Effective control of COVID-19 MESHD
requires antivirals directed against SARS-CoV-2 virus. Here we assess ten available HCV protease inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS- CoV-2 Mpro PROTEIN
and HCV NS3/4A proteases, and virtual docking experiments show that all ten HCV drugs can potentially bind into the Mpro PROTEIN
binding cleft. Seven of these HCV drugs inhibit SARS-CoV-2 Mpro PROTEIN
protease activity, while four dock well into the PLpro PROTEIN
substrate binding cleft MESHD
and inhibit PLpro PROTEIN
protease activity. These same seven HCV drugs inhibit SARS-CoV-2 virus replication in Vero and/or human cells, demonstrating that HCV drugs that inhibit Mpro PROTEIN
, or both Mpro PROTEIN
and PLpro PROTEIN
, suppress virus replication. Two HCV drugs, simeprevir and grazoprevir synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, thereby increasing remdesivir inhibitory activity as much as 10-fold.
HighlightsO_LISeveral HCV protease inhibitors are predicted to inhibit SARS-CoV-2 Mpro PROTEIN
and PLpro PROTEIN
C_LIO_LISeven HCV drugs inhibit Mpro PROTEIN
enzyme activity, four HCV drugs inhibit PLpro PROTEIN
C_LIO_LISeven HCV drugs inhibit SARS-CoV-2 replication in Vero and/or human cells.
C_LIO_LIHCV drugs simeprevir and grazoprevir synergize with remdesivir to inhibit SARS- CoV-2.
eTOC blurbBafna MESHD
, White and colleagues report that several available hepatitis C MESHD
virus drugs inhibit the SARS-CoV-2 Mpro PROTEIN
and/or PLpro PROTEIN
proteases and SARS-CoV-2 replication in cell culture. Two drugs, simeprevir and grazoprevir, synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir antiviral activity as much as 10-fold.
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