Comparison of Newly Assembled Full Length HIV-1 Integrase With Prototype Foamy Virus Integrase: Structure-Function Prospective

Abstract

BackgroundDrug design against human immunodeficiency virus type 1 (HIV-1) integrase through its mechanistic study is of great interest in the area in biological research. The main obstacle in this area is the absence of the full-length crystal structure for HIV-1 integrase to be used as a model. A complete structure, similar to HIV-1 of a prototype foamy virus integrase in complex with DNA, including all conservative residues, is available and has been extensively used in recent investigations.ObjectivesThe aim of this study was to determine whether the above model is precisely representative of HIV-1 integrase. This would critically determine the success of any designed drug using the model in deactivation of integrase and AIDS treatment.Materials and MethodsPrimarily, a new structure for HIV-1 was constructed, using a crystal structure of prototype foamy virus as the starting structure. The constructed structure of HIV-1 integrase was simultaneously simulated with a prototype foamy virus integrase on a separate occasion.ResultsOur results indicate that the HIV-1 system behaves differently from the prototype foamy virus in terms of folding, hydration, hydrophobicity of binding site and stability.ConclusionsBased on our findings, we can conclude that HIV-1 integrase is vastly different from the prototype foamy virus integrase and does not resemble it, and the modeling output of the prototype foamy virus simulations could not be simply generalized to HIV-1 integrase. Therefore, our HIV-1 model seems to be more representative and more useful for future research.

Chelation Motifs Affecting Metal-dependent Viral Enzymes: N′-acylhydrazone Ligands as Dual Target Inhibitors of HIV-1 Integrase and Reverse Transcriptase Ribonuclease H Domain

“…In fact, compounds 15, 18 and 23 are predicted to establish secondary interactions with PFV residues Asp185, Tyr212, and Glu221, which correspond to HIV IN Asp116, Tyr143 and Glu152 (Dayer, 2016). Moreover, compound 23 establish additional secondary interactions with the hydroxyl group of Tyr212 and with the nitrogen of the peptidic bridge between Asp185 and Gln186.…”

“…Intriguingly, striking similarities can be seen in the coordination modes proposed for the best compound 18 and compounds 15 and 23 compared to those of some 3-hydroxypyrimidine-2,4-dione-5-N-benzylcarboxamides, recently described as potent inhibitors of HIV-1 IN and RNase H ( Wu et al, 2016 ). In fact, compounds 15, 18 and 23 are predicted to establish secondary interactions with PFV residues Asp185, Tyr212, and Glu221, which correspond to HIV IN Asp116, Tyr143 and Glu152 ( Dayer, 2016 ). Moreover, compound 23 establish additional secondary interactions with the hydroxyl group of Tyr212 and with the nitrogen of the peptidic bridge between Asp185 and Gln186.…”

Coronavirus (2019-nCoV) Deactivation via Spike Glycoprotein Shielding by Old Drugs, Bioinformatic Study

“…In order to study the dynamic behavior of spike proteins especially at RBD and fusion core we performed molecular dynamic simulations using double-precision MPI version of GROMACS 4.5.5 installed on UBUNTU version 16.04 with GROMOS force field for 20 ns at 37degrees centigrade and 1 atmosphere [29].…”

Structural Insights on Retroviral DNA Integration: Learning from Foamy Viruses

“…Some studies have raised doubts on HIV-1 IN inhibitor screening platforms using PFV-IN, indicating that the HIV-1 IN system behaves differently from PFV in terms of folding, recognition, and hydrophobicity of the tDNA binding site, and stability [82]. Although conformational changes and the energy landscape are still unclear, the molecular docking and molecular dynamics study validates the reliability of the platform and reestablishes PFV IN as one of the most credible surrogate model for HIV-1 INSTIs studies and anti-AIDS drug development based on IN structure.…”