Study of Oxadiazole derivatives as precursor for multi-functional inhibitor to SARS-CoV-2: A detailed virtual screening analysis

Authors

DOI:

https://doi.org/10.5564/mjc.v25i51.2909

Keywords:

COVID-19, Oxadiazole, transmembrane-serine, 3-chymotrypsin-like-protease, angiotensin-converting-enzyme

Abstract

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is highly contagious and has caused widespread loss of life. In the quest to find effective antiviral agents, attention has turned to oxadiazole derivatives, which are known for their potential antiviral properties in such as CoViTris2020, ChloViD2020, etc. To evaluate their effectiveness, molecular docking and molecular dynamics simulations are conducted for various oxadiazole derivative in interactions with critical proteins involved in the viral infection process. These proteins encompass transmembrane-serine-2 (TMPRSS2), 3-chymotrypsin-like-protease (3CLpro), angiotensin-converting-enzyme-2 (ACE2), and papain-like-protease (PLpro). The study shows that the oxadiazole derivatives exhibited their most stable complexes when interacting with TMPRSS2 in comparison to 3CLpro, ACE2, and PLpro. In particular, Oxa8 displayed a binding energy of -6.52 kcal/mol with TMPRSS2. In contrast, the binding energies with ACE2, 3CLpro, and PLpro were -5.74, -4.56, and -5.56 kcal/mol, respectively. RMSD analysis during MD simulations demonstrated that the complex structure remained consistently stable. During the initial 2 ns, the RMSD value for the ligand concerning its interaction with the protein backbone hovered around 2 Å, indicating a sustained level of structural stability. In conclusion, this study suggests that oxadiazole derivative Oxa8 holds promise as a potential inhibitor of SARS-CoV-2, particularly due to its strong binding affinity with TMPRSS2 and its enduring structural stability observed in molecular dynamics simulations.

Downloads

Download data is not yet available.
Abstract
152
PDF 212

References

Zhou H., Yang J., Zhou C., Chen B., Fang H., et al. (2021) Review of SARS-CoV2: compared with SARS-CoV and MERS-CoV. Front. Med., (Lausanne) 8, 628370. https://doi.org/10.3389/fmed.2021.628370

Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., et al. (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271-80. https://doi.org/10.1016/j.cell.2020.02.052

Cevik M., Tate M., Lloyd O., Maraolo A.E., Schafers J., Ho A. (2021) SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: A systematic review and meta-analysis. Lancet Microbe, 2(1), e13-22. https://doi.org/10.1016/S2666-5247(20)30172-5

Domling A., Gao L. (2020) Chemistry and Biology of SARS-CoV-2. Chem., 6(6), 1283-95. https://doi.org/10.1016/j.chempr.2020.04.023

Rabie A.M. (2021) CoViTris2020 and ChloViD2020: A striking new hope in COVID-19 therapy. Mol. Diversity, 25, 1839. https://doi.org/10.1007/s11030-020-10169-0

Rabie A.M. (2021) Two antioxidant 2,5-disubstituted-1,3,4-oxadiazoles (CoViTris2020 and ChloViD2020): Successful repurposing against COVID-19 as the first potent multitarget anti-SARS-CoV-2 drugs. New J. Chem., 45, 761. https://doi.org/10.1039/D0NJ03708G

Janardhanan J., Chang M., Mobashery S. (2016) The oxadiazole antibacterials. Current Opinion in Microbiology, 33, 13-17. https://doi.org/10.1016/j.mib.2016.05.009

Boström J., Hogner A., Llinàs A., Wellner E., Plowright A.T. (2012) Oxadiazoles in medicinal chemistry. J. Med. Chem., 55(5), 1817-30. https://doi.org/10.1021/jm2013248

Siwach A., Verma. (2020) Therapeutic potential of oxadiazole or furadiazole containing compounds. BMC Chemistry, 14, 70. https://doi.org/10.1186/s13065-020-00721-2

Glomb T., Świątek P. (2021) Antimicrobial activity of 1,3,4-oxadiazole derivatives. Int. J. Mol. Sci., 22(13), 6979. https://doi.org/10.3390/ijms22136979

Vaidya A., Jain S., Jain P., Jain P., Tiwari et al. (2016) Synthesis and biological activities of oxadiazole derivatives: A review. Mini Reviews in Medicinal Chemistry, 16(10), 825-845. https://doi.org/10.2174/1389557516666160211120835

Bajaj S., Roy P.P., Singh J. (2017) 1,3,4-oxadiazoles as telomerase inhibitor: Potential anticancer agents. Anti-Cancer Agents in Medicinal Chemistry, 17(14), 1869-1883. https://doi.org/10.2174/1871521409666170425092906

Meng H.-W., Shen Z.-B., Meng X.-S., Yin Z.-Q., Wang X.-R. et al. (2023) Novel flavonoid 1,3,4-oxadiazole derivatives ameliorate MPTP-induced Parkinson's disease via Nrf2/NF-κB signaling pathway. Bioorg. Chem., 138, 106654. https://doi.org/10.1016/j.bioorg.2023.106654

Naseem S., Temirak A., Imran A., Jalil S., Fatima S., et al. (2023) Therapeutic potential of 1,3,4-oxadiazoles as potential lead compounds for the treatment of Alzheimer's disease. RSC Adv., 13, 17526. https://doi.org/10.1039/D3RA01953E

Kumar S. (2022) Curcumin as a potential multiple-target inhibitor against SARS- ip CoV-2 infection: A detailed interaction study using quantum chemical calculations. J. Serb. Chem. Soc., 88(4), 381-394. https://doi.org/10.2298/JSC220921087K

Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 181(2), 281-292. https://doi.org/10.1016/j.cell.2020.02.058

Kumar V., Kumar R., Kumar N., Kumar S. (2023) Solvation dynamics of oxadiazoles as a potential candidate for drug preparation. Asian J. Chem., 35. https://doi.org/10.14233/ajchem.2023.27594

Somani R.R., Shirodkar P.Y. (2009) Oxadiazole: A biologically important heterocycle Der Pharma Chemica,1(1), 130-140.

Van Der Spoel D., Lindahl E., Hess B., Groenhof G., Mark A.E., Berendsen H.J., (2005) GROMACS: Fast, flexible, and free. J. Comput. Chem., 26, 1701. https://doi.org/10.1002/jcc.20291

Bjelkmar P., Larsson P., Cuendet M.A., Hess B., Lindahl E., (2010) Implementation of the CHARMM force field in GROMACS: Analysis of protein stability effects from correction maps, virtual interaction sites, and water models. J. Chem. Theory Comput., 6 459. https://doi.org/10.1021/ct900549r

MacKerell A.D.Jr, Banavali N., Foloppe N., (2000) Development and current status of the CHARMM force field for nucleic acids. Biopolymers, 56(4), 257-65. https://doi.org/10.1002/1097-0282(2000)56:4<257::AID-BIP10029>3.0.CO;2-W

Kumar S.P., Kumar S., Fazal A.D., Bera S., (2023) Molecular aggregation kinetics of heteropolyene: An experimental, topological and solvation dynamics studies. Journal of Photochemistry and Photobiology A: Chemistry, 445 115084. https://doi.org/10.1016/j.jphotochem.2023.115084

Kumar S.P., Kumar S., (2023) Weak intra and intermolecular interactions via aliphatic hydrogen bonding in piperidinium based ionic liquids: Experimental, topological and molecular dynamics studies. J. Mol. Liq., 375, 121354. https://doi.org/10.1016/j.molliq.2023.121354

Kumar S., Singh S.K., Vaishnav J.K., Hill J.G., Das A. (2017) Interplay among electrostatic, dispersion, and steric interactions: Spectroscopy and quantum chemical calculations of π-hydrogen bonded complexes. Chem. Phys. Chem., 18(7), 828-838. https://doi.org/10.1002/cphc.201601405

Kumar S., Singh S.K., Calabrese C., Maris A., et al. (2014) Structure of saligenin: Microwave, UV and IR spectroscopy studies in a supersonic jet combined with quantum chemistry calculations. Phys. Chem. Chem. Phys., 16, 17163-17171. https://doi.org/10.1039/C4CP01693A

Kumar S., Mukherjee A., Das A. (2012) Structure of Indole•••Imidazole heterodimer in a supersonic jet: A gas phase study on the interaction between the aromatic side chains of tryptophan and histidine residues in proteins. J. Phys. Chem., A 116(47), 11573-11580. https://doi.org/10.1021/jp309167a

Abraham M.J., Murtola T., Schulz R., Páll S., Smith J.C., et al. (2015) GROMACS: High-performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1, 19-25. https://doi.org/10.1016/j.softx.2015.06.001

Berendsen H.J., van der Spoel D., van Drunen R. (1995) GROMACS: A message-passing parallel molecular dynamics implementation. Comput. Phys. Commun., 91(1-3), 43-56. https://doi.org/10.1016/0010-4655(95)00042-E

Downloads

Additional Files

Published

2024-02-01

How to Cite

Kumar, V., & Kumar, S. (2024). Study of Oxadiazole derivatives as precursor for multi-functional inhibitor to SARS-CoV-2: A detailed virtual screening analysis. Mongolian Journal of Chemistry, 25(51). https://doi.org/10.5564/mjc.v25i51.2909

Issue

Section

Articles