In Search of Multi-Stage Mutation Resistant HIV Drugs: A DFT Study

Abstract

Aims: Searching of highly active (activity at the pico molar level) multi-stage, mutation registrant HIV-1 drug through theoretical and computational methodologies. Background: Recent advances of computational methodology to predict the important properties of a drug, like IC50, LogP, CC50, etc., assist in model and in-silico characterization of compounds as drug for variant deadly diseases. The drug potency of thio-propionate derivatives of iron, ruthenium and osmium carbonyl clusters are reported as less toxic,water-soluble, easy metabolic and effective as cancer drugs. Objective: The study of the drug-like activity of organo-metallic clusters of group-8 metals as HIV drug using the latest computational aids is the objective of the present research. Method: Quantum computational methodologies are used to predict the IC50, and LogP, CC50 of the modeled compounds. Density Functional Theory (DFT) calculations are used where it is required. Molecular docking methods are used for the study of the metabolic probability of the compound which has the best activity as an HIV drug. Result: It is observed that IC50 of Ru5(CO)14(µ−H)(µ−S(CH2)2COO−)Na+ is only 220 pico-mole as HIV-1 capsid -A inhibitor. Its inhibition activities in other enzymatic processes involved in the HIV life cycle in the human body are also studied and compared with the most used market available drugs. This modeled compound has supreme activity and less toxicity compared to the FDA approved drugs chosen for the comparison. Conclusion: From this study, it could be concluded that this modeled compound would be a multi-stage, mutation resistant HIV drug. Other: These findings would enrich the HIV drug search. Funding Statement: None to declare Declaration of Interests: None to declare