Computational hunting of natural active compounds as an alternative for Remdesivir to target RNA-dependent polymerase

• Published in: Cellular and Molecular Biology 2021-01, Vol.67 (1), p.45-49
• Main Authors: Saeed, Mohd, Saeed, Amir, Alam, Md Jahoor, Alreshidi, Mousa
• Format: Article
• Language: English
• ISSN: 0145-5680; 1165-158X
• DOI: 10.14715/cmb/2021.67.1.7

The hunt for potential lead/drug molecules from different resources, especially from natural resources, for possible treatment of COVID-19 is ongoing. Several compounds have already been identified, but only a few are good enough to show potential against the virus. Among the identified druggable target proteins of SARS-CoV-2, this study focuses on non-structural RNA-dependent RNA polymerase protein (RdRp), a well-known enzyme for both viral genome replication and viral mRNA synthesis, and is therefore considered to be the primary target. In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as ꞌ-6.29 kcal/mol and 58.39 µMꞌ, and ꞌ-7.93kcal/mol and 45.3 µMꞌ, respectively. The finding indicated that the selected hits (Cyclocurcumin and Silybin B) could act as non-nucleotide anti-polymerase agents, and can be further optimized as a potential inhibitor of RdRp by benchwork experiments.