Background: Lack of effective early-stage HIV-1 inhibitor instigated the need for screening
of novel gp120-CD4 binding inhibitor. Polyphenols, a secondary metabolite derived from natural
sources are reported to have broad spectrum HIV-1 inhibitory activity. However, the gp120-CD4
binding inhibitory activity of polyphenols has not been analysed in silico yet.
Objectives: To establish the usage of phytopolyphenols (Theaflavin, Epigallocatechin (EGCG), Ellagic
acid and Gallic acid) as early stage HIV-1 inhibitor by investigating their binding mode in reported
homology of gp120-CD4 receptor complex using in silico screening studies and in vitro cell
Methods: The in silico molecular docking and molecular simulation studies were performed using
Schrödinger 2013-2 suite installed on Fujitsu Celsius Workstation. The in vitro cell line studies were
performed in the TZM-bl cell line using MTT assay and β-galactosidase assay.
Results: The results of molecular docking indicated that Theaflavin and EGCG exhibited high XP
dock score with binding pose exhibiting Van der Waals interaction and hydrophobic interaction at
the deeper site in the Phe43 cavity with Asp368 and Trp427. Both Theaflavin and EGCG form a
stable complex with the prepared HIV-1 receptor and their binding mode interaction is within the
vicinity 4 Å. Further, in vitro cell line studies also confirmed that Theaflavin (SI = 252) and EGCG
(SI = 138) exert better HIV-1 inhibitory activity as compared to Ellagic acid (SI = 30) and Gallic
acid (SI = 34).
Conclusion: The results elucidate a possible binding mode of phytopolyphenols, which pinpoints
their plausible mechanism and directs their usage as early stage HIV-1 inhibitor.