Individual and common inhibitors of coronavirus and picornavirus main proteases.
Picornaviruses (PV) and coronaviruses (CoV) are positive-stranded RNA viruses which infect millions of people worldwide each year, resulting in a wide range of clinical outcomes. As reported in this study, using high throughput screening against approximately 6800 small molecules, we have identified several novel inhibitors of SARS-CoV 3CL(pro) with IC(50) of low microM. Interestingly, one of them equally inhibited both 3C(pro) and 3CL(pro) from PV and CoV, respectively. Using computer modeling, the structural features of these compounds as individual and common protease inhibitors were elucidated to enhance our knowledge for developing anti-viral agents against PV and CoV.
Kuo
Chih-Jung
CJ
Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan, ROC.
Liu
Hun-Ge
HG
Lo
Yueh-Kuei
YK
Seong
Churl-Min
CM
Lee
Kee-In
KI
Jung
Young-Sik
YS
Liang
Po-Huang
PH
D000595:Amino Acid Sequence; D003198:Computer Simulation; D017124:Conserved Sequence; D017934:Coronavirus / Q000187:drug effects* / Q000201:enzymology*; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010849:Picornaviridae / Q000187:drug effects* / Q000201:enzymology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D010447:Peptide Hydrolases