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Conservation Analysis of HIV-1 Protein Sequences Reveal Potential Drug Binding Sites: A Case of Viral Protein U and Protease

Vinay Choudhary Darapaneni, Jayalakshmi Sakhamuri, vivek darapaneni


The HIV-1 viral protein U (Vpu) and protease play a pivotal role in the infectious lifecycle of human immunodeficiency virus-1. The objective of this study is to find the degree of conservation of the viral protein U (Vpu) and protease protein and to detect conserved binding sites, which might be used as target sites for potential anti-Vpu and anti-protease drugs. The conservation analysis was based on 4231 amino acid sequences for Vpu and 13,457 amino acid sequences for protease. The conservation analysis revealed a number of conserved and variable residues. The universally conserved residues identified in this study might be involved in either structure stabilizing or protein-protein interactions. The novel conserved potential binding sites which have been identified are: Vpu (Ile39, Arg45, Ile46 and Gly71) and protease (Pro9, Thr80 and Asn83). Along with conservational analysis, structural analysis revealed novel binding sites, namely four conserved sites on Vpu (Arg49, Ala50, Ser53, Gly54, Gly59; Glu56, Ser57, Asp60; Glu56, Gly71; Glu48, Glu51, Asp52, Gly54-Glu56) and single novel conserved site on protease (Thr4, Trp6 and Arg87, Asn88, Thr91, Gln92). The outcome of this study provides the basis for developing anti-Vpu and anti-protease drugs which have abridged potential to induce drug resistance through mutations.


Vpu, Protease; Conservation; Drugs; Mutation; Resistance; HIV-1; Binding sites


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