Indones. J. Chem., 2020, 20 (6), 1430 - 1440 Muhammad Arba et al. 1430 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 1,* , Andry Nur-Hidayat 1 , Ida Usman 2 , Arry Yanuar 3 , Setyanto Tri Wahyudi 4 , Gilbert Fleischer 5 , Dylan James Brunt 5 , and Chun Wu 5,** 1 Faculty of Pharmacy, Universitas Halu Oleo, Kendari 93232, Indonesia 2 Department of Physics, Universitas Halu Oleo, Kendari 93232, Indonesia 3 Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia 4 Department of Physics, IPB University, Bogor 16680, Indonesia 5 Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States * Corresponding author: email: muh.arba@uho.ac.id * ; wuc@rowan.edu ** Received: May 16, 2020 Accepted: August 3, 2020 DOI: 10.22146/ijc.56120 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. Keywords: Covid-19; herbal; ZINC; RdRp, in silico; coronavirus ■ INTRODUCTION The novel coronavirus disease in 2019 (Covid-19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared as a pandemic across the world as it impacts all countries worldwide with more than two million people infected and hundred thousand fatalities [1]. The current situation still has the potential to elevate considering its rapid contagious nature and no drug or vaccine for this particular coronavirus has been found until recently. This necessitates the urgent effort to find small molecules with the potential to inhibit specific proteins of the coronavirus. Antiviral drug discovery including the 2019 novel coronavirus is subjected to the specific proteins responsible for the viral life cycle continuation. One of the druggable proteins with the potential to target is RNA-dependent RNA polymerase (RdRp) which belongs to the nucleic acid polymerase. The crucial function of RdRp is its role in catalyzing the synthesis of the viral