Machine Learning-Enhanced Computational Approaches for Chikungunya Drug Discovery: Integrating Molecular Docking, Toxicity Prediction, Pharmacophore Analysis

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Authors

Oluwasegun Babaleye¹

1. The Nigeria Institute of Medical Research

Conference / event

Addressing the Health Challenge in Africa: A Decade of Building Worldclass and Innovative Scientific Capacity, July 2024 (Accra, Ghana)

Poster summary

The Chikungunya virus (CHIKV) is a mosquito-borne alphavirus from the Togaviridae family, causing Chikungunya fever. It is mainly transmitted by Aedes mosquitoes, including Aedes aegypti and Aedes albopictus, which also spread dengue and Zika viruses. Other transmission routes include blood transfusions and mother-to-child transmission. Symptoms typically appear 2 to 12 days after infection, with sudden high fever, joint pain, muscle pain, headache, and rash. A study used PubChem compounds and a convolutional neural network (CNN) to predict binding affinity to CHIKV protease, achieving a Mean Squared Error (MSE) of 4.35 and a Concordance Index (CI) of 0.805. Molecular docking identified Baicalein and Epigallocatechin gallate (EGCG) as potential inhibitors. Further research is needed to assess their clinical efficacy and safety.

Keywords

Chikungunya virus (CHIKV), Machine learning, Molecular docking, Pharmacophore

Research areas

Medicine, Biological Sciences, Immunology, Genetics, Bioinformatics and Genomics

References

1. Baker, R.E., Mahmud, A.S., Miller, I.F. et al. Infectious disease in an era of global change. Nat Rev Microbiol 20, 193–205 (2022). https://doi.org/10.1038/s41579-021-00639-z. r, R.E., Mahmud, A.S., Miller, I.F. et al. Infectious disease in an era of global change. Nat Rev Microbiol 20, 193–205 (2022). https://doi.org/10.1038/s41579-021-00639-z.
2. Bewick V, Cheek L, Ball J. Statistics review 7: Correlation and regression. Crit Care. 2003 Dec;7(6):451-9. doi: 10.1186/cc2401. Epub 2003 Nov 5. PMID: 14624685; PMCID: PMC374386.
3. Caglioti C, Lalle E, Castilletti C, Carletti F, Capobianchi MR, Bordi L. Chikungunya virus infection: an overview. New Microbiol. 2013 Jul;36(3):211-27. Epub 2013 Jun 30. PMID: 23912863.
4. Chauhan K, Jandu JS, Brent LH, et al. Rheumatoid Arthritis. [Updated 2023 May 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441999/
5. Dias DA, Urban S, Roessner U. A historical overview of natural products in drug discovery. Metabolites. 2012 Apr 16;2(2):303-36. doi: 10.3390/metabo2020303. PMID: 24957513; PMCID: PMC3901206.
6. D'Souza S, Prema KV, Balaji S, Shah R. Deep Learning-Based Modeling of Drug-Target Interaction Prediction Incorporating Binding Site Information of Proteins. Interdiscip Sci. 2023 Jun;15(2):306-315. doi: 10.1007/s12539-023-00557-z. Epub 2023 Mar 26. PMID: 36967455; PMCID: PMC10148762.
7. Ferrari E, Bettuzzi S, Naponelli V. The Potential of Epigallocatechin Gallate (EGCG) in Targeting Autophagy for Cancer Treatment: A Narrative Review. Int J Mol Sci. 2022 May 28;23(11):6075. doi: 10.3390/ijms23116075. PMID: 35682754; PMCID: PMC9181147.
8. Saisawang C, Sillapee P, Sinsirimongkol K, Ubol S, Smith DR, Ketterman AJ. Full length and protease domain activity of chikungunya virus nsP2 differ from other alphavirus nsP2 proteases in recognition of small peptide substrates. Biosci Rep. 2015 Apr 22;35(3):e00196. doi: 10.1042/BSR20150086. PMID: 26182358; PMCID: PMC4445351.
9. Singh, Sunit, Unni, Salini. Chikungunya virus: Host-pathogen interaction, 2011/03/01, Reviews in medical virology. 10.1002/rmv.681.
10. Zeller H, Van Bortel W, Sudre B. Chikungunya: Its History in Africa and Asia and Its Spread to New Regions in 2013-2014. J Infect Dis. 2016 Dec 15;214(suppl 5): S436-S440. doi: 10.1093/infdis/jiw391. PMID: 27920169.

Funding

1. no funding

Supplemental files

No data provided

Additional information

Competing interests

No competing interests were disclosed.

Data availability statement

The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.

Creative Commons license

Copyright © 2024 Babaleye. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.