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

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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.

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This work has been published as a preprint version (https://www.biorxiv.org/content/10.1101/2021.09.09.459559v1.full) and additional updates are available to the preprint version.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science, Muğla Sıtkı Koçman University, Kötekli, 48121, Muğla, Turkey

    Naeem Abdul Ghafoor

  2. Bioengineering Department, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey

    Kevser Kübra Kırboğa

  3. Informatics Institute, Istanbul Technical University, Maslak, 34469, Istanbul, Turkey

    Kevser Kübra Kırboğa

  4. Molecular Microbiology Unit, Department of Molecular Biology and Genetics, Faculty of Science, Muğla Sıtkı Koçman University, Kötekli, 48121, Muğla, Turkey

    Ömür Baysal

  5. Department of Computer Engineering, Faculty of Engineering, Muğla Sıtkı Koçman University, Kötekli, 48000, Muğla, Turkey

    Barış Ethem Süzek

  6. Center for Research and Practice in Biotechnology and Genetic Engineering, Istanbul University, Vezneciler, Fatih, 34119, Istanbul, Turkey

    Ragıp Soner Silme

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  1. Naeem Abdul Ghafoor
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Contributions

NAG: formal analysis; writing—original draft preparation. KKK: conceptualisation; investigation; formal analysis; writing—review & editing—original draft preparation. ÖB: conceptualisation; investigation; formal analysis; writing—original draft preparation—writing—review & editing. BES: investigation; formal analysis. RSS: conceptualisation; formal analysis; writing—original draft preparation. All authors commented on previous versions and read and approved the final manuscript.

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Correspondence to Ömür Baysal.

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The study is dedicated to the memory of the late Prof. Dr. Randall J. Cohrs.

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Ghafoor, N.A., Kırboğa, K.K., Baysal, Ö. et al. Data mining and molecular dynamics analysis to detect HIV-1 reverse transcriptase RNase H activity inhibitor. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10707-6

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