Data mining and molecular dynamics analysis to detect HIV-1 reverse transcriptase RNase H activity inhibitor

Naeem Abdul Ghafoor; Kevser Kübra Kırboğa; Ömür Baysal; Barış Ethem Süzek; Ragıp Soner Silme

doi:10.1007/s11030-023-10707-6

Data mining and molecular dynamics analysis to detect HIV-1 reverse transcriptase RNase H activity inhibitor

Mol Divers. 2023 Aug 10. doi: 10.1007/s11030-023-10707-6. Online ahead of print.

Authors

Naeem Abdul Ghafoor¹, Kevser Kübra Kırboğa^{2

3}, Ömür Baysal⁴, Barış Ethem Süzek⁵, Ragıp Soner Silme⁶

Affiliations

¹ Department of Molecular Biology and Genetics, Faculty of Science, Muğla Sıtkı Koçman University, Kötekli, 48121, Muğla, Turkey.
² Bioengineering Department, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey.
³ Informatics Institute, Istanbul Technical University, Maslak, 34469, Istanbul, Turkey.
⁴ Molecular Microbiology Unit, Department of Molecular Biology and Genetics, Faculty of Science, Muğla Sıtkı Koçman University, Kötekli, 48121, Muğla, Turkey. omurbaysal@mu.edu.tr.
⁵ Department of Computer Engineering, Faculty of Engineering, Muğla Sıtkı Koçman University, Kötekli, 48000, Muğla, Turkey.
⁶ Center for Research and Practice in Biotechnology and Genetic Engineering, Istanbul University, Vezneciler, Fatih, 34119, Istanbul, Turkey.

PMID: 37561229
DOI: 10.1007/s11030-023-10707-6

Abstract

HIV-1 is a deadly virus that affects 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 effect of RNase H activity on viral replication and the interaction of Phomoarcherin B with other HIV-1 proteins should be investigated.

Keywords: Computational biology; Drug discovery; HIV-1; Molecular docking; Molecular dynamics; Pol gene; Reverse-transcriptase RNase H.