Background: HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the
replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains
of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and
RNase H domain of RT shares striking structural similarity; it contains conserved DDE triad (two
aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain.
Objective: To search for novel compounds with dual inhibition of IN and RNase H for the drug
development against both wild and drug-resistant strains of HIV.
Methods: In the present work, attempts have been made to search compounds against both IN and
the RNase H domain of RT. Using structure-based virtual screening approach; Asinex database of
small molecules was screened against the viral IN. Top thirty ranked hits obtained, were further
evaluated against RNase H domain of RT using Extra Precision (XP) mode of Glide docking.
Furthermore, eleven common potential hits were observed which were subjected to the in-silico
prediction of drug-likeness properties. Later on, molecular dynamics simulation was performed for
the best common active hit (AS6), in the complex with selected enzymes.
Result: In silico screening of Asinex database compounds against IN and RNase H resulted in total
seven compounds namely AS3, AS5, AS6, AS15, AS17, AS18, and AS20 having dual inhibition
Conclusion: This study warrants the dual inhibition activity of AS6 against IN and RNase H
confirms its anti-HIV activity.