In silico evaluation of compounds from Hypericum perforetum for anti-HIV activity

Abstract Only a few medications are approved for the treatment of infected patients, despite the prevalence of HIV infection around the world and the absence of effective treatments for AIDS patients. The search for innovative anti-HIV medications with novel mechanisms of action and initiatives to lower attrition rates in the early stages of drug discovery is urgently needed. This study's goal is to assess Hypericum perforetum compounds for anti-HIV-1 activity after giving reported potential anti-HIV-1 leads priority. A series of recognised compounds from the medicinal plant H. perforetum were subjected to in silico HIV lead prioritisation. These molecules' energy-minimized architectures were docked with HIV-Protease. Using Autodock software, docking tests were conducted, and highly positive contacts between these compounds and the HIV-1 protease enzyme were found. With a higher docking score, occimene was discovered to be in the lead. Eight H. perforetum compounds were docked into HIV-1 protease in the current work, and one molecule, E-Beta-Ocimene, suggested that residues Asp29, Ile47, Val32, Leu76, and Pro79 might be crucial for the binding of these compounds. The findings indicated that there is room to increase the activity of occimene analogues in order to find an effective anti-HIV drug. References Brown, R. Qiang, P.J. Stadnik, L.J. Stotts, J.A. Von Arx. Virtual humans for implantable device safety assessment in MRI: mitigating magnetic resonance imaging hazards for implanted medical devices. IEEE Pulse, 8 (4) (2017), pp. 50-53. Fujimoto, L.M. Angelone, E. Lucano, S.S. Rajan, M.I. Iacono. Radio-frequency safety assessment of stents in blood vessels during magnetic resonance imaging Front. Physiol., 9 (2018), p. 1439. Grandi, S. Morotti, E. Pueyo, B. Rodriguez. Editorial: safety pharmacology - risk assessment QT interval prolongation and beyond. Front. Physiol., 9 (2018), p. 678. Gujjeti, R. P., & Mamidala, E. (2014). Anti-HIV activity and cytotoxic effects of Aerva lanata root extracts. American Journal of Phytomedicine and Clinical Therapeutics, 2(7), 894-900. Hunter, N.P. Smith The cardiac physiome project J. Physiol. (Lond.), 594 (23) (2016), pp. 6815-6816. Jean-Quartier, F. Jeanquartier, I. Jurisica, A. Holzinger. In silico cancer research towards 3R. BMC Cancer, 18 (1) (2018), p. 408. NACO. India HIV Estimates 2021. Fact Sheet. MoHFW, GoI, 2022. Pappalardo, G. Russo, F.M. Tshinanu, M. Viceconti. In silico clinical trials: concepts and early adoptions. Brief. Bioinformatics (2018). Parvinian, et al. Credibility evidence for computational patient models used in the development of physiological closed-loop controlled devices for critical care medicine. Front. Physiol., 10 (2019), p. 220. Passini, et al. Human in silico drug trials demonstrate higher accuracy than animal models in predicting clinical pro-arrhythmic cardiotoxicity. Front. Physiol., 8 (2017), p. 668. Pellizzer, C.A.A. Lemos, D.A.F. Almeida, V.E. de Souza Batista, J.F. Santiago Júnior, F.R. Verri. Biomechanical analysis of different implant-abutments interfaces in different bone types: an in silico analysis. Mater. Sci. Eng. C Mater. Biol. Appl., 90 (2018), pp. 645-650. Rodriguez, et al. Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop Europace, 18 (9) (2016), pp. 1287-1298. Swapna, K., Srujana, M., & Estari, M. (2022). Inhibitory effect against reverse transcriptase of HIV-1 of the extract of selected medicinal plants. International Journal of Health Sciences, 6(S5), 10623–10633. https://doi.org/10.53730/ijhs.v6nS5.10841 Viceconti, E. Dall’Ara. From bed to bench: How in silico medicine can help ageing research. Mech. Ageing Dev., 177 (2019), pp. 103-108