In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors

Published: 16 March 2023
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  • Saipul Maulana Master Program of Department Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
  • Tutik Sri Wahyuni Department Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Center for Natural Products Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
  • Prihartini Widiyanti Biomedical Engineering, Faculty of Science and Technology, Universitas Airlangga, Surabaya; Institute of Tropical Disease (ITD), Universitas Airlangga, Surabaya, Indonesia.
  • Muhammad Sulaiman Zubair Faculty of Science, Department of Pharmacy, University of Tadulako, Palu, Indonesia.

Background: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has been discovered, searching for its inhibitors by in silico technique becomes possible.

Objective: This study aims to virtually screen the potential of phytoconstituents from the Begonia genus as 3Cl pro-SARS-CoV- 2 inhibitors, based on its crucial role in viral replication, hence making these proteases “promising” for the anti-SARS-CoV-2 target.

Methods: In silico screening was carried out by molecular docking on the web-based program DockThor and validated by a retrospective method. Predictive binding affinity (Dock Score) was used for scoring the compounds. Further molecular dynamics on Desmond was performed to assess the complex stability.

Results: Virtual screening protocol was valid with the area under curve value 0.913. Molecular docking revealed only β-sitosterol-3-O-β-D-glucopyranoside with a lower docking score of - 9.712 kcal/mol than positive control of indinavir. The molecular dynamic study showed that the compound was stable for the first 30 ns simulations time with Root Mean Square Deviation <3 Å, despite minor fluctuations observed at the end of simulation times. Root Mean Square Fluctuation of catalytic sites HIS41 and CYS145 was 0.756 Å and 0.773 Å, respectively.

Conclusions: This result suggests that β-sitosterol-3-O-β-D- glucopyranoside might be a prospective metabolite compound that can be developed as anti-SARS-CoV-2.

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Maulana, S., Wahyuni, T. S., Widiyanti, P., & Zubair, M. S. (2023). <em>In silico</em> screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors. Journal of Public Health in Africa, 14(s1).


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