Design and Identification of Potential HIV-1 Entry Inhibitors Using In Silico Click Chemistry and Molecular Modeling Methods
Andrianov A.M.1, Yushkevich A.M.2, Bosko I.P.2, Karpenko A.D.2, Kornoushenko Yu.V.1, Furs K.V.2, Tuzikov A.V.2
1Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus
2United Institute of Informatics Problems, National Academy of Sciences of Belarus
Abstract. An integrated approach including the click chemistry methodology, molecular docking, quantum mechanics, and molecular dynamics was used to computer-aided design of potential HIV-1 inhibitors able to block the membrane-proximal external region (MPER) of HIV-1 gp41, which plays an important role in the fusion of the viral and host cell membranes. Evaluation of the binding efficiency of the designed compounds to the HIV-1 MPER peptide was performed using the methods of molecular modeling, resulting in nine chemical compounds exhibiting high-affinity binding to this functionally important site of the trimeric “spike” of the viral envelope. The data obtained indicate that the identified compounds are promising for the development of novel antiviral drugs, HIV fusion inhibitors blocking the early stages of HIV infection.
Key words: HIV-1, gp41 protein, membrane-proximal external region, HIV fusion inhibitors, molecular modeling, antiviral drugs.