Currently available antiviral drugs target the pol-encoded retroviral enzymes or integrases, in addition,
inhibitors that target HIV-1 envelope-receptor interactions have also been recently approved. Recent understanding
of the interactions between HIV-1 and host restriction factors has provided fresh avenues for development
of novel antiviral drugs. For example, viral infectivity factor (Vif) now surfaced as an important therapeutic target in
treatment of HIV infection. Vif suppresses A3G antiviral activity by targeting these proteins for polyubiquitination and proteasomal
degradation. In the present study we analyzed the inhibitory potential of VEC5 and RN18 to inhibit the Vif-A3G interaction
through protein- protein docking studies. Perusal of the study showed that, VEC5 and RN18 though inhibits the interaction
however showed sub optimal potential. To overcome this set back, we identified 35 structural analogues of VEC5
and 18 analogues of RN18 through virtual screening approach. Analogue with PubCID 71624757 and 55358204
(AKOS006479723) -structurally akin to VEC5 and RN18 respectively showed much appreciable interaction than their respective
parent compound. Evident from Vif-A3G; protein - protein docking studies, analogue PubCID 71624757 demonstrated
1.08 folds better inhibitory potential than its parent compound VEC5 while analogue PubCID 55358204 was 1.15
folds better than RN18. Further these analogues passed drug likeness filters and predicted to be non- toxic. We expect these
analogues can be put to pharmacodynamic studies that can pave way the breakthrough in HIV therapeutics.
Keywords: Protein - Protein docking, RN18, VEC5, Vif, Vif inhibitors, VIF-A3G interactions, Virtual Screening.
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