Unveiling the molecular activity of HIV towards the CD4: A study based on subtype C via docking and dynamics approach.

Background: Acquired Immunodeficiency Syndrome (AIDS) is a critical global health issue caused by the human immunodeficiency virus (HIV). It has different strains and subtypes; among these, Subtype C accounts for higher infection rates than others. Despite its high prevalence, the molecular interactions with host receptors, specifically CD4, have not yet been explored.

Methods: This study investigates the molecular interactions between HIV subtype C and the CD4 receptor via docking and dynamics approach. Four HIV targets were examined, and their structure was modelled. Subsequently, these models were docked with the CD4 to analyze their binding interaction. The stability was examined over 200 simulations via Desmond software, and trajectories were analyzed, followed by Root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the radius of gyration (Rg), PCA (principal component analysis), etc., to assess their stability and interaction dynamics.

Results: The four target structures were modelled, and their quality was validated. Further, the docking analysis with CD4 revealed that the Envelope glycoprotein has -13.6 kcal/mol, protease has -11.2 kcal/mol, Reverse transcriptase has -12.4 kcal/mol, and integrase has -13.1 kcal/mol binding affinity towards it, followed by the number of hydrogen bond, such as 9, 6, 11, 6. The simulation over 200 ns demonstrated that the average RMSD for each complex started stabilizing within the 0.9 Å - 3.4 Å, followed by 25-50 ns, whereas the RMSF, Rg and PCA revealed the relative compactness and flexibility varied across different viral targets.

Conclusions: The study successfully identified the interactive residues of HIV subtype C toward the CD4 receptor. The binding affinities and stability data provide valuable insights into Subtype C's molecular interactions with the host, and these findings underscore the potential for developing treatments that disrupt these interactions to combat HIV more effectively.