Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease

摘要: To date, no suitable vaccine or specific antiviral drug is available to treat Chikungunya viral (CHIKV) fever. Hence, it essential identify candidates that could potentially impede CHIKV infection. Here, we present the development of a homology model nsP2 protein based on crystal structure Venezuelan equine encephalitis virus (VEEV). The modeled was optimized using molecular dynamics simulation; junction peptides nonstructural complex were then docked in order investigate possible protein-protein interactions between and proteins cleaved by nsP2. modeling studies conducted shed light binding modes, critical with provide insight into chemical features needed inhibit CHIK Energy-optimized pharmacophore mapping performed peptides. Based results, propose must be an inhibitor protease. resulting contained aromatic ring, hydrophobic three hydrogen-bond donor sites. Using these features, screened large public library compounds (Asinex, Maybridge, TOSLab, Binding Database) find potential ligand protein. yielded fitness score more than 1.0 further subjected Glide HTVS XP. report best four their docking scores; have IDs 27943, 21362, ASN 01107557 01541696. We bind active site protease this enzyme. Furthermore, backbone structural scaffolds lead serve as building blocks when designing drug-like molecules for treatment