Molecular modeling studies of peptide drug candidates against SARS.
Flexible alignment and docking studies were conducted for the three octapeptides, ATLQANEV, AVLQSGFR, and ATLQAIAS, that were cleavable by SARS-CoV Mpro. It has been observed that all pharmacophores of the three peptides overlap very well, and that ATLQANEV binds best with the receptor, followed by AVLQSGFR, and then ATLQAIAS. During the process of docking the octapeptides to the SARS enzyme, the residues of the catalytic dyad, i.e., His-41 and Cys-145 are actively involved in forming the hydrogen bonds, so is the center residue (Gln) of all the three octapeptides. The findings are fully consistent with experimental observations. The present studies suggest that the octapeptides ATLQANEV and ATLQAIAS, like AVLQSGFR, might also be the good starting points for designing potential drugs against SARS.
Zhang
Rui
R
Tianjin Institute of Bioinformatics and Drug Discoveries and Tianjin Normal University, China.
Wei
Dong-Qing
DQ
Du
Qi-Shi
QS
Chou
Kuo-Chen
KC
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*
D000998:Antiviral Agents; D010455:Peptides