In silico screening of natural compounds for antiviral activity against the influenza virus
DOI:
https://doi.org/10.60988/p.v37i2S.207Keywords:
in silico; influenza virus; natural compounds; neuraminidase; antiviralAbstract
Influenza A viruses are major pathogens responsible for significant global morbidity and mortality, necessitating the development of novel antiviral agents targeting drug-resistant strains. This study has assessed the antiviral potential of various natural compounds against influenza A by performing molecular docking analyses in order to evaluate their binding affinities with neuraminidase (Protein Data Bank identifier: 3TI6); a critical viral enzyme that facilitates progeny virion release and dissemination. A total of 5,749 unique phytoconstituents were computationally screened, yielding five candidates with high binding affinities: pentagalloylglucose (-15.238 kcal/mol), stachyurin (-12.833 kcal/mol), osyritin (-12.398 kcal/mol), stachysoside A (-12.166 kcal/mol), and repandusinic acid A (-11.911 kcal/mol). Molecular dynamics simulations of repandusinic acid A corroborated the docking results and geometry optimization data, demonstrating enhanced structural stability and conformational flexibility relative to analogous compounds, with a root mean square deviation of 0.147 Å. These findings indicate that the identified bioactive compounds, particularly repandusinic acid A, hold promise as antiviral agents targeting neuraminidase. However, extensive experimental validation is required in order to elucidate their therapeutic efficacy, toxicity profiles, and pharmacokinetic parameters in clinical contexts.
References
1. Ashraf M.A., Raza M.A., Amjad M.N., Ud Din G., Yue L., Shen B., et al. A comprehensive review of influenza B virus, its biological and clinical aspects. Front. Microbiol. 15, 1467029, 2024. DOI: 10.3389/fmicb.2024.1467029
2. Huang Q.J., Song K., Xu C., Bolon D.N.A., Wang J.P., Finberg R.W., et al. Quantitative structural analysis of influenza virus by cryo-electron tomography and convolutional neural networks. Structure 30(5), 777–786, e3, 2022. DOI: 10.1016/j.str.2022.02.014
3. Lampejo T. Influenza and antiviral resistance: an overview. Eur. J. Clin. Microbiol. Infect. Dis. 39(7), 1201–1208, 2020. DOI: 10.1007/s10096-020-03840-9
4. Zhao J.H., Wang Y.W., Yang J., Tong Z.J., Wu J.Z., Wang Y.B., et al. Natural products as potential lead compounds to develop new antiviral drugs over the past decade. Eur. J. Med. Chem. 260, 115726, 2023. DOI: 10.1016/j.ejmech.2023.115726
5. Fraga-Corral M., Otero P., Cassani L., Echave J., Garcia-Oliveira P., Carpena M., et al. Traditional applications of tannin rich extracts supported by scientific data: chemical composition, bioavailability and bioaccessibility. Foods 10(2), 251, 2021. DOI: 10.3390/foods10020251
6. Márquez-Domínguez L., Jasso-Miranda C., Sedeño-Monge V., Santos-López G. Non-analog compounds to sialic acid as inhibitors of influenza virus neuraminidase: an underexplored approach for novel antivirals – systematic review. Sci. Pharm. 92(2), 33, 2024. DOI: 10.3390/scipharm92020033
7. Xu J., Luo Q., Huang Y., Li J., Ye W., Yan R., et al. Influenza neuraminidase mutations and resistance to neuraminidase inhibitors. Emerg. Microbes Infect. 13(1), 2429627, 2024. DOI: 10.1080/22221751.2024.2429627
8. Javaid A., Bibi N., Mahmood M.S., Batool H., Batool S., Hamid A., et al. Screening of natural compounds as inhibitor of Mpro SARS-CoV-2 protein; a molecular dynamics approach. Curr. Pharm. Des. 31(7), 559–574, 2025. DOI: 10.2174/0113816128315762240828052002
9. Saber M.M., Salama M.M., Badary O.A. The potential of natural products in the management of COVID-19. Adv. Exp. Med. Biol. 1457, 215–235, 2024. DOI: 10.1007/978-3-031-61939-7_12
