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

• Published in: Virologica Sinica 2021-12, Vol.36 (6), p.1421-1430
• Main Authors: Zhou, Mengxin, Han, Yutong, Li, Mengxia, Ye, Gang, Peng, Guiqing
• Format: Article
• Language: English
• Subjects: Animals; Antiviral agents; Antiviral Agents - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cats; Cell viability; Chlorocebus aethiops; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus Infections - drug therapy; Coronavirus Infections - veterinary; Coronavirus, Feline - drug effects; Coronaviruses; Diarrhea; Epidemics; Feline infectious peritonitis; Fluorescence resonance energy transfer; Gastrointestinal diseases; Hydrogen bonding; Kidneys; Medical Microbiology; Microbial Genetics and Genomics; Microbiology; Molecular Docking Simulation; Molecular modelling; Molecular weight; Oncology; Peritonitis; Research Article; Swine; Swine Diseases - virology; Vero Cells; Virology; Vomiting
• ISSN: 1674-0769; 1995-820X
• DOI: 10.1007/s12250-021-00415-6

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 (3CL pro ) of PEDV. These compounds are of low molecular weight (MW) and greatly inhibited the activity of this enzyme (IC 50 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 EC 50 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 3CL pro 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.