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

• Main Authors: Saipul Maulana (Author), Tutik S. Wahyuni (Author), Prihartini Widiyanti (Author), Muhammad S. Zubair (Author)
• Format: Book
• Published: AOSIS, 2023-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2038-9922; 2038-9930; 10.4081/jphia.2023.2508
• Keywords: begonia; sars-cov-2; 3-chymotrypsin-like protease (3clpro); molecular docking; molecular dynamics; Public aspects of medicine; RA1-1270
• Source: Journal of Public Health in Africa, Vol 14, Iss 1 (2023)

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.