Year: 2012
Type: article
Abstract: Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV) delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41) which advances through four distinct conformational states: (i) native, (ii) pre-hairpin intermediate, (iii) fusion active (fusogenic), and (iv) post-fusion. The pre-hairpin intermediate is a particularly attractive step for therapeutic intervention given that gp41 N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) domains are transiently exposed prior to the formation of a six-helix bundle required for fusion. Most peptide-based inhibitors, including the FDA-approved drug T20, target the intermediate and there are significant efforts to develop small molecule alternatives. Here, we review current approaches to studying interactions of inhibitors with gp41 with an emphasis on atomic-level computer modeling methods including molecular dynamics, free energy analysis, and docking. Atomistic modeling yields a unique level of structural and energetic detail, complementary to experimental approaches, which will be important for the design of improved next generation anti-HIV drugs.
Source: Biology
Authors: William J. Allen, Robert C. Rizzo
Institution: Stony Brook University
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W2000406617