Virtual Screening of the Indonesian Medicinal Plant and Zinc Databases for Potential Inhibitors of the RNA-Dependent RNA Polymerase (RdRp) of 2019 Novel Coronavirus

Muhammad Arba; Andry Nur-Hidayat; Ida Usman; Arry Yanuar; Setyanto Tri Wahyudi; Gilbert Fleischer; Dylan James Brunt; Chun Wu

doi:10.22146/ijc.56120

Virtual Screening of the Indonesian Medicinal Plant and Zinc Databases for Potential Inhibitors of the RNA-Dependent RNA Polymerase (RdRp) of 2019 Novel Coronavirus

https://doi.org/10.22146/ijc.56120

Muhammad Arba^(1*), Andry Nur-Hidayat⁽²⁾, Ida Usman⁽³⁾, Arry Yanuar⁽⁴⁾, Setyanto Tri Wahyudi⁽⁵⁾, Gilbert Fleischer⁽⁶⁾, Dylan James Brunt⁽⁷⁾, Chun Wu⁽⁸⁾

(1) Faculty of Pharmacy, Universitas Halu Oleo, Kendari 93232, Indonesia
(2) Faculty of Pharmacy, Universitas Halu Oleo, Kendari 93232, Indonesia
(3) Department of Physics, Universitas Halu Oleo, Kendari 93232, Indonesia
(4) Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia
(5) Department of Physics, IPB University, Bogor 16680, Indonesia
(6) Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States
(7) Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States
(8) Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States
(*) Corresponding Author

Abstract

The novel coronavirus disease 19 (Covid-19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a pandemic across the world, which necessitate the need for the antiviral drug discovery. One of the potential protein targets for coronavirus treatment is RNA-dependent RNA polymerase. It is the key enzyme in the viral replication machinery, and it does not exist in human beings, therefore its targeting has been considered as a strategic approach. Here we describe the identification of potential hits from Indonesian Herbal and ZINC databases. The pharmacophore modeling was employed followed by molecular docking and dynamics simulation for 40 ns. 151 and 14480 hit molecules were retrieved from Indonesian herbal and ZINC databases, respectively. Three hits that were selected based on the structural analysis were stable during 40 ns, while binding energy prediction further implied that ZINC1529045114, ZINC169730811, and 9-Ribosyl-trans-zeatin had tighter binding affinities compared to Remdesivir. The ZINC169730811 had the strongest affinity toward RdRp compared to the other two hits including Remdesivir and its binding was corroborated by electrostatic, van der Waals, and nonpolar contribution for solvation energies. The present study offers three hits showing tighter binding to RdRp based on MM-PBSA binding energy prediction for further experimental verification.

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DOI: https://doi.org/10.22146/ijc.56120