P1 and P1? para-fluoro phenyl groups show enhanced binding and favorable predicted pharmacological properties: Structure-based virtual screening of extended lopinavir analogs against multi-drug resistant HIV-1 protease
Three libraries of extended lopinavir analogs were designed for docking analysis. Lead compound (14) with favorable binding and pharmacological properties was identified using virtual screening. Compound 14 has para-fluoro phenyl groups as P1 and P1? moieties. Compound 14 showed favorable binding affinity against wild type and an ensemble of MDR HIV-1 protease variants. Compound 14 restored lost contacts in the expanded active site cavity of MDR HIV-1 protease. Compound 14 showed favorable pharmacological properties as other FDA approved protease inhibitors.
virtual screening lopinavir hiv-1 protease protease inhibitors hiv/aids multidrug-resistance