期刊
JOURNAL OF CLINICAL MEDICINE
卷 9, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/jcm9082399
关键词
Middle East respiratory syndrome; coronavirus; RNA-dependent RNA polymerase; cell-based reporter assay; nucleoside analog; remdesivir
资金
- National Research Council of Science & Technology (NST) - Korea government (MSIT) [CRC-16-01-KRICT, NSN1621350]
- 'National Research Council of Science & Technology (NST)-Korea Institute of Oriental Medicine (KIOM)' Postdoctoral Research Fellowship for Young Scientists at the Korea Institute of Oriental Medicine in South Korea
Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19) are emerging zoonotic diseases caused by coronavirus (CoV) infections. The viral RNA-dependent RNA polymerase (RdRp) has been suggested as a valuable target for antiviral therapeutics because the sequence homology of CoV RdRp is highly conserved. We established a cell-based reporter assay for MERS-CoV RdRp activity to test viral polymerase inhibitors. The cell-based reporter system was composed of the bicistronic reporter construct and the MERS-CoV nsp12 plasmid construct. Among the tested nine viral polymerase inhibitors, ribavirin, sofosbuvir, favipiravir, lamivudine, zidovudine, valacyclovir, vidarabine, dasabuvir, and remdesivir, only remdesivir exhibited a dose-dependent inhibition. Meanwhile, the Z-factor and Z '-factor of this assay for screening inhibitors of MERS-CoV RdRp activity were 0.778 and 0.782, respectively. Ribavirin and favipiravir did not inhibit the MERS-CoV RdRp activity, and non-nucleoside HCV RdRp inhibitor, dasabuvir, partially inhibited MERS-CoV RdRp activity. Taken together, the cell-based reporter assay for MERS-CoV RdRp activity confirmed remdesivir as a direct inhibitor of MERS-CoV RdRp in cells. A cell-based MERS-CoV RdRp activity reporter assay is reliable and accurate for screening MERS-CoV RdRp-specific inhibitors. It may provide a valuable platform for developing antiviral drugs for emerging CoV infections.
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