Molecular docking study of ruthenium-p-cymene complexes with isothiazole derivatives as SARS-CoV-2 main protease inhibitors

2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023 (387-390)

АУТОР(И) / AUTHOR(S): Marko Radovanović, Ignjat Filipović, Maja Đukić, Marija Ristić, Ivan Jakovljević, Zoran D. Matović

Е-АДРЕСА / E-MAIL: marko.radovanovic@pmf.kg.ac.rs

Download Full Pdf   

DOI: 10.46793/ICCBI23.387R

САЖЕТАК / ABSTRACT:

Since proper treatment for COVID-19 still has not been developed, exploration of novel options is required. Activities of different metal complexes, promising results gained from examining different thiazole derivatives, and research in the field of natural products like p-cymene, produced an idea to test piano stool ruthenium p-cymene complexes with isothiazole derivatives as ligands. In silico methods are often used as the first step in a series of experiments during the development of new drugs, and docking simulations are a quick way to determine the feasibility of novel compounds as potential inhibitors of target enzymes. Existing compounds of ruthenium with published crystal structures were tested against the main protease of SARS-CoV-2. All of the tested compounds show a potential ability to bind to the target enzyme, while the compound with phenyl and morpholinyl substituents in isothiazole ligand shows the best activity among tested compounds. Authors feel confident that further research on this topic will yield compounds with even better potential activities against the main protease of the SARS-CoV-2.

КЉУЧНЕ РЕЧИ / KEYWORDS:

ruthenium, p-cymene, isothiazole, docking, SARS-CoV-2

ЛИТЕРАТУРА / REFERENCES:

  • X. Yang, Y. Yu, J. Xu, H. Shu, H. Liu, Y. Wu, L. Zhang, Z. Yu, M. Fang, T. Yu, Y. Wang., Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study, Lancet Respiratory Medicine, 8 (2020) 475-481.
  • L. Dai, G.F. Gao., Viral targets for vaccines against COVID‐19, Nature Reviews Immunology, 21 (2021) 73‐82.
  • K. Ioannou, M.C. Vlasiou., Metal-based complexes against SARS-CoV-2, Biometals, 35 (2022) 639-652.
  • A. Panagiotopoulos, M. Tseliou, I. Karakasiliotis, D. Kotzampasi, V. Daskalakis, N. Kesesidis, G. Notas, C. Lionis, M. Kampa, S. Pirintsos, G. Sourvinos, E. Castana., p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein, Pharmacology Research & Perspectives, 9 (2021) e00798.
  • R.W. Elsayed, M.A. Sabry, H.I. El-Subbagh, S.M. Bayoumi, S.M. El-Sayed., Thiazole-based SARS-CoV-2 protease (COV Mpro) inhibitors: Design, synthesis, enzyme inhibition, and molecular modeling simulations, Archiv der Pharmazie, 355 (2022) e2200121.
  • M.K. Looi., What are the latest covid drugs and treatments?, BMJ, 381 (2023) p872.
  • M.B. Djukić, M.S. Jeremić, I.P. Filipović, O.R. Klisurić, R.M. Jelić, S. Popović, S. Matić, V. Onnis, Z.D. Matović., Ruthenium(II) Complexes of Isothiazole Ligands: Crystal Structure, HSA/DNA Interactions, Cytotoxic Activity and Molecular Docking Simulations, ChemistrySelect, 5 (2020) 11489.
  • M.B. Đukić, M.S. Jeremić, I.P. Filipović, O.R. Klisurić, V.V. Kojić, D.S. Jakimov, R.M. Jelić, V. Onnis, Z.D. Matović., Synthesis, characterization, HSA/DNA interactions and antitumor activity of new [Ru(η6-p-cymene)Cl2(L)] complexes, Journal of Inorganic Biochemistry, 213 (2020) 111256.
  • G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson., Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity, Journal of Computational Chemistry, 16 (2009) 2785-2791.
  • Z. Jin, X. Du, Y. Xu, Y. Deng, M. Liu, Y. Zhao, B. Zhang, X. Li, L. Zhang, C. Peng, Y. Duan, J. Yu, L. Wang, K. Yang, F. Liu, R. Jiang, X. Yang, T. You, X. Liu, X. Yang, F. Bai, H. Liu, X. Liu, L.W. Guddat, W. Xu, G. Xiao, C. Qin, Z. Shi, H. Jiang, Z. Rao, H. Yang., Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature, 582 (2020) 289–293.
  • C. Huang, P. Wei, K. Fan, Y. Liu, L. Lai., 3C-like Proteinase from SARS Coronavirus Catalyzes Substrate Hydrolysis by a General Base Mechanism, Biochemistry, 43 (2004) 4568–4574.