Data mining and molecular dynamics analysis to detect HIV-1 reverse transcriptase RNase H activity inhibitor
MOLECULAR DIVERSITY, vol.1, pp.1-20, 2023 (Scopus)
- Publication Type: Article / Article
- Volume: 1
- Publication Date: 2023
- Doi Number: 10.1007/s11030-023-10707-6
- Journal Name: MOLECULAR DIVERSITY
- Journal Indexes: Scopus, BIOSIS, Chemical Abstracts Core, MEDLINE
- Page Numbers: pp.1-20
- Istanbul University Affiliated: Yes
Abstract
HIV-1 is a deadly virus that afects millions of people worldwide. In this study, we aimed to inhibit viral replication by
targeting one of the HIV-1 proteins and identifying a new drug candidate. We used data mining and molecular dynamics
methods on HIV-1 genomes. Based on MAUVE analysis, we selected the RNase H activity of the reverse transcriptase (R.T)
enzyme as a potential target due to its low mutation rate and high conservation level. We screened about 94,000 small molecule inhibitors by virtual screening. We validated the hit compounds' stability and binding free energy through molecular
dynamics simulations and MM/PBSA. Phomoarcherin B, known for its anticancer properties, emerged as the best candidate
and showed potential as an HIV-1 reverse transcriptase RNase H activity inhibitor. This study presents a new target and drug
candidate for HIV-1 treatment. However, in vitro and in vivo tests are required. Also, the efect of RNase H activity on viral
replication and the interaction of Phomoarcherin B with other HIV-1 proteins should be investigated.