Open Access Open Access  Restricted Access Subscription or Fee Access

In silico evaluation for the repurposing of antiviral drugs towards multiple targets of monkey pox viral disease

Addala Gowtham Venkat Sai

Abstract


Objective: Monkeypox is a growing public health problem. The disease is caused by the monkeypox virus. The latest epidemic has been linked to previously unknown mutations and variations. Tecovirimat is a poxvirus medication that has been licenced by the US Food and Drug Administration (FDA). Otherwise, there is little pharmacopoeia and scientific interest in
monkeypox. Computational screening and molecular interactions were used in this work to investigate the possible repurposing of numerous medications already authorised by the FDA or other regulatory bodies for alternative purposes. Major known proteins A48R, Nucleoside Analog & D13L, Capsid protein inhibitor, inhibition of these proteins results in suppressing viral replication. Methods: In current research, 70 antiviral drugs were chosen to examine their binding affinities with targeted proteins (A48R & D13L). Molecular docking was done with the tool PyRx, the practical tool. The progress was done computationally with data and structures retrieved from the databases DRUG BANK & PDB. The structure validation of proteins was done with the tools PDBsum generate and BIOVIA the discovery studio software. ADMET screening was done using ADMET filters to examine the pharmacological properties. Results: Since the ligands Fosdagrocorat, Hypericin, Lixivaptan,  Maraviroc & Saquinavir
shown the least binding affinity towards the viral proteins. Conclusion: The ligands were suitable for using as an antiviral drug in maintenance of monkeypox virus. The examined ligands may supress the activity of viral replication and control the progression of virus. The drug repurposing provides an idea about the drugs that might be helpful in management and treatment of monkeypox disease.


Full Text:

PDF

References


Lam, H. Y. I., Guan, J. S., & Mu, Y. (2022). In Silico Repurposed Drugs against Monkeypox

Virus. Molecules, 27(16), 5277. https://doi.org/10.3390/molecules27165277

Gessain, A., Nakoune, E., & Yazdanpanah, Y. (2022). Monkeypox. New England Journal of

Medicine, 387(19), 1783-1793.

Rabaan, A. A., Abas, A. H., Tallei, T. E., Al‐Zaher, M. A., Al‐Sheef, N. M., Al‐Nass, E.

Z., ... & Bin Emran, T. (2022). Monkeypox Outbreak 2022: What We Know So Far and Its

Potential Drug Targets and Management Strategies. Journal of Medical Virology.

Rizk, J. G., Lippi, G., Henry, B. M., Forthal, D. N., & Rizk, Y. (2022). Prevention and

treatment of monkeypox. Drugs, 1-7.

Lum, F. M., Torres-Ruesta, A., Tay, M. Z., Lin, R. T., Lye, D. C., Rénia, L., & Ng, L. F.

(2022). Monkeypox: disease epidemiology, host immunity and clinical interventions. Nature

Reviews Immunology, 22(10), 597-613.

Mercorelli, B., Palù, G., & Loregian, A. (2018). Drug repurposing for viral infectious

diseases: how far are we?. Trends in microbiology, 26(10), 865-876.

Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C,

Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L,

Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the

DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The Protein Data

Bank. Nucleic Acids Res [Internet]. 2000;28(1):235–42.

Panikar S, Shoba G, Arun M, Sahayarayan JJ, Usha Raja Nanthini A, Chinnathambi A, et al.

Essential oils as an effective alternative for the treatment of COVID-19: Molecular

interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties. J

Infect Public Health [Internet]. 2021;14(5):601–10. Available from:

http://dx.doi.org/10.1016/j.jiph.2020.12.037

Laskowski RA. PDBsum: summaries and analyses of PDB structures. Nucleic Acids Res

[Internet]. 2001;29(1):221–2. Available from: http://dx.doi.org/10.1093/nar/29.1.221

Fabregat A, Sidiropoulos K, Viteri G, Marin-Garcia P, Ping P, Stein L, D'Eustachio P,

Hermjakob H. Reactome diagram viewer: data structures and strategies to boost performance.

Bioinformatics. 2018 Apr 1;34(7):1208-1214. doi: 10.1093/bioinformatics/btx752. PubMed

PMID: 29186351.

Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: a powerful

approach for structure-based drug discovery. Current computer-aided drug design, 7(2),

–157. https://doi.org/10.2174/157340911795677602

Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with

PyRx. In Chemical biology (pp. 243-250). Humana Press, New York, NY.

Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, et al. ADMETlab 2.0: an integrated online

platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids

Res [Internet]. 2021;49(W1):W5–14. Available from: http://dx.doi.org/10.1093/nar/gkab255

Caillat, C., Topalis, D., Agrofoglio, L. A., Pochet, S., Balzarini, J., Deville-Bonne, D., &

Meyer, P. (2008). Crystal structure of poxvirus thymidylate kinase: an unexpected

dimerization has implications for antiviral therapy. Proceedings of the National Academy of

Sciences of the United States of America, 105(44), 16900–16905.

https://doi.org/10.1073/pnas.0804525105

Garriga, D., Headey, S., Accurso, C., Gunzburg, M., Scanlon, M., & Coulibaly, F. (2018).

Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin.

Proceedings of the National Academy of Sciences of the United States of America, 115(33),

–8429. https://doi.org/10.1073/pnas.1810398115

Srivastava, V., Naik, B., Godara, P., & Prusty, D. (2022). Identification of FDA-approved

drugs with triple targeting mode of action for the treatment of Monkeypox: a high throughput

virtual screening study.




DOI: https://doi.org/10.37628/ijaba.v9i1.846

Refbacks

  • There are currently no refbacks.