Two Inhibitors Against the 3C-Like Proteases of Swine Coronavirus and Feline Coronavirus

Mengxin Zhou, Yutong Han, Mengxia Li, Gang Ye, Guiqing Peng

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Coronaviruses (CoVs) are important human and animal pathogens that cause respiratory and gastrointestinal diseases. Porcine epidemic diarrhoea (PED), characterized by severe diarrhoea and vomiting in pigs, is a highly lethal disease caused by porcine epidemic diarrhoea virus (PEDV) and causes substantial losses in the swine industry worldwide. However, currently available commercial drugs have not shown great therapeutic effects. In this study, a fluorescence resonance energy transfer (FRET)-based assay was applied to screen a library containing 1,590 compounds and identified two compounds, 3-(aminocarbonyl)-1-phenylpyridinium and 2,3-dichloronaphthoquinone, that target the 3C-like protease (3CLpro) of PEDV. These compounds are of low molecular weight (MW) and greatly inhibited the activity of this enzyme (IC50 values were obtained in this study). Furthermore, these compounds exhibited antiviral capacity against another member of the CoV family, feline infectious peritonitis virus (FIPV). Here, the inhibitory effects of these compounds against CoVs on Vero cells and feline kidney cells were identified (with EC50 values) and cell viability assays were performed. The results of putative molecular docking models indicate that these compounds, labeled compound 1 and compound 2, contact the conserved active sites (Cys144, Glu165, Gln191) of 3CLpro via hydrogen bonds. These findings provide insight into the antiviral activities of compounds 1 and 2 that may facilitate future research on anti-CoV drugs.

Original languageEnglish (US)
Pages (from-to)1421-1430
Number of pages10
JournalVirologica Sinica
Volume36
Issue number6
DOIs
StatePublished - Dec 2021
Externally publishedYes

Bibliographical note

Funding Information:
We thank Professor Yunfeng Song for his valuable suggestions on the manuscript. This work was supported by the National Key R&D Plan of China (grant no. 2018YFD0500102) and the Natural Science Foundation of Hubei Province of China (grant no. 2016CFA069).

Publisher Copyright:
© 2021, Wuhan Institute of Virology, CAS.

Keywords

  • 3C-like Protease
  • Coronavirus (CoVs)
  • Feline infectious peritonitis virus (FIPV)
  • Inhibitor
  • Porcine epidemic diarrhoea virus (PEDV)

PubMed: MeSH publication types

  • Journal Article

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