Molecular docking analysis of zidovudine triphosphate with conserved residues from NS3 protein

Dengue fever poses a significant global health concern, yet despite extensive research there is no specific antiviral therapy against the infection. Therefore, it is of interest to study the interaction between the highly conserved N-terminal of NS3 protein of DENV-4 and an FDA approved antiviral, zidovudine triphosphate (ZDV-TP), using molecular docking and molecular dynamics (MD) simulation studies. Docking showed significant binding between NS3 protein and ZDV-TP with -7.7 kcal/mol of binding energy. ZDV-TP interacted with the conserved and active site residues of N-terminal NS3 protease including Gly133, Thr134, Ser135, Gly151 and Asn152. These residues are crucial for viral replication and are highly conserved in all the serotypes of DENV. MD simulation studies showed that the NS3-ZDV-TP complex had no major conformational instability with an approximately linear trajectory up to 200 ns simulation. ZDV-TP was well anchored at its binding position and minimized the compactness as compared to NS3 protein only, indicating high affinity for NS3.