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




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


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.


Download data is not yet available.


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.

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.

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.

Domling A., Gao L. (2020) Chemistry and Biology of SARS-CoV-2. Chem., 6(6), 1283-95.

Rabie A.M. (2021) CoViTris2020 and ChloViD2020: A striking new hope in COVID-19 therapy. Mol. Diversity, 25, 1839.

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.

Janardhanan J., Chang M., Mobashery S. (2016) The oxadiazole antibacterials. Current Opinion in Microbiology, 33, 13-17.

Boström J., Hogner A., Llinàs A., Wellner E., Plowright A.T. (2012) Oxadiazoles in medicinal chemistry. J. Med. Chem., 55(5), 1817-30.

Siwach A., Verma. (2020) Therapeutic potential of oxadiazole or furadiazole containing compounds. BMC Chemistry, 14, 70.

Glomb T., Świątek P. (2021) Antimicrobial activity of 1,3,4-oxadiazole derivatives. Int. J. Mol. Sci., 22(13), 6979.

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.

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.

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.

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.

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.

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.

Kumar V., Kumar R., Kumar N., Kumar S. (2023) Solvation dynamics of oxadiazoles as a potential candidate for drug preparation. Asian J. Chem., 35.

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.

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.

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.<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.

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.

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.

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.

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.

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.

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.


Additional Files



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), 1–10.