Abstract: International Journal of Molecular Sciences Article Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2 Shailima Rampogu 1,2,† , Gihwan Lee 1,† , Jun Sung Park 2,† , Keun Woo Lee 1, * and Myeong Ok Kim 2, * 1 2 * †



 Citation: Rampogu, S.; Lee, G.; Park, J.S.; Lee, K.W.; Kim, M.O. Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2. Int. J. Mol. Sci. 2022, 23, 1771. https://doi.org/ 10.3390/ijms23031771 Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Korea; shailima.rampogu@gmail.com (S.R.); pika0131@naver.com (G.L.) Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; jsp@gnu.ac.kr Correspondence: kwlee@gnu.ac.kr (K.W.L.); mokim@gnu.ac.kr (M.O.K.) These authors contributed equally to this work. Abstract: Recently, the world has been witnessing a global pandemic with no effective therapeutics yet, while cancer continues to be a major disease claiming many lives. The natural compound curcumin is bestowed with multiple medicinal applications in addition to demonstrating antiviral and anticancer activities. In order to elucidate the impact of curcumin on COVID-19 and cancer, the current investigation has adapted several computational techniques to unfold its possible inhibitory activity. Accordingly, curcumin and similar compounds and analogues were retrieved and assessed for their binding affinities at the binding pocket of SARS-CoV-2 main protease and DDX3. The best binding pose was escalated to molecular dynamics simulation (MDS) studies to assess the time dependent stability. Our findings have rendered one compound that has demonstrated good molecular dock score complemented by key residue interactions and have shown stable MDS results inferred by root mean square deviation (RMSD), radius of gyration (Rg), binding mode, hydrogen bond interactions, and interaction energy. Essential dynamics results have shown that the systemadapts minimum energy conformation to attain a stable state. The discovered compound (curA) could act as plausible inhibitor against SARS-CoV-2 and DDX3. Furthermore, curA could serve as a chemical scaffold for designing and developing new compounds. Keywords: natural compound analogues; main protease; SARS-CoV-2; DDX3; dual inhibitor Academic Editors: Priyanka Banerjee and Robert Preissner Received: 1 January 2022 Accepted: 27 January 2022 Published: 4 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).