Bazı HIV-1 Düşük Düzey Viremi Suşlarında Etravirin'e Karşı Dirençlerin In-Silico ve In- Vitro Yöntemlerle Araştırılması

Abstract

Human Immunodeficiency Virus (HIV) is a significant virus that, when left uncontrolled, leads to Acquired Immunodeficiency Syndrome (AIDS), a clinical condition characterized by the transmission of its genetic material to host immune system cells. To manage HIV infection and eliminate its transmissibility, antiretroviral therapy (ART) agents are employed. These agents function by inhibiting HIV proteins. Etravirine (ETR) is one of the non-nucleoside reverse transcriptase enzyme inhibitors. Low-Level Viremia (LLV) refers to the persistence of viral load in HIV-positive individuals who are under ongoing ART. The sustained viral load is a significant concern, as it indicates the continued transmissibility of HIV in infected individuals and may ultimately progress to AIDS. LLV is believed to result from virological failure, drug absorption issues, and mutation-induced drug resistance.

In our study, we investigated Etravirine (ETR) resistance using in-silico methods, specifically focusing on the following mutations: Lys104Gln, Lys102Gln, Lys101Arg-Lys104Arg, Ser191Phe, Ile94Leu-Lys104Arg, Lys104Glu-His235Leu, Ala98Ser, and Val179Ile. These mutations were analyzed in the reverse transcriptase (RT) enzyme obtained from strains of HIV-positive individuals with Low-Level Viremia (LLV). These mutations are located in the vicinity of the ETR inhibition site. The ETR resistance conferred by the Lys104Gln, Lys102Gln, Lys101Arg-Lys104Arg, Ser191Phe, Ile94Leu-Lys104Arg, Lys104Glu-His235Leu, Ala98Ser, and Val179Ile mutations was investigated using homology modeling, molecular docking, and protein-ligand interaction analysis methods.

Our study suggests that Ala98Ser and Val179Ile mutations, which have not been previously analyzed through in-silico methods, induce conformational changes in the binding region of the reverse transcriptase (RT) enzyme. These changes are believed to lead to a low level of resistance to Etravirine (ETR).