Targeting the Crimean-Congo haemorrhagic fever virus with natural compounds: an in silico study
DOI:
https://doi.org/10.60988/p.v37i2S.206Keywords:
in silico; Crimean-Congo haemorrhagic fever virus; natural compounds; FDA-approved drugs; antiviral drugsAbstract
The Crimean-Congo haemorrhagic fever virus (CCHFV) is a highly transmissible pathogen capable of inducing severe haemorrhagic manifestations with high fatality rates. This study has aimed at demonstrating a virtual screening workflow and compound selection strategy to evaluate the potential of natural compounds to inhibit CCHFV through its ovarian tumor domain protease (vOTU); a key mediator of immune evasion. From a curated library of 5,749 natural compounds, five candidates met the selection criteria. Among these, 1,3,6-trigalloyl glucose exhibited the highest binding affinity (XP GScore: -9.351 kcal/mol) and geometric stability, as evidenced by a root mean square deviation (RMSD) of <4.5 Å in molecular dynamics simulations. The second most promising compound, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-(6-deoxy-α-L-gulopyranosyl)-β-D-talopyranoside, demonstrated an XP GScore of -7.909 kcal/mol and an RMSD <2.8 Å. These findings suggest that the identified natural compounds may serve as promising antiviral candidates against CCHFV. Further experimental validation is warranted in order to assess their therapeutic potential. Overall, this study underscores the utility of in silico approaches for the identification of novel antiviral agents derived from natural sources.
References
1. Khan M.A., Zafar S. Addressing the ripple effect of Crimean-Congo hemorrhagic fever in Pakistan and the imminent risk of a global health crisis. Infect. Dis. Clin. Microbiol. 6(3), 252–254, 2024. DOI: 10.36519/idcm.2024.430
2. Di Bella S., Babich S., Luzzati R., Cavasio R.A., Massa B., Braccialarghe N., et al. Crimean-Congo haemorrhagic fever (CCHF): present and future therapeutic armamentarium. Infez. Med. 32(4), 421–433, 2024. DOI: 10.53854/liim-3204-2
3. Rodriguez S.E., Hawman D.W., Sorvillo T.E., O’Neal T.J., Bird B.H., Rodriguez L.L., et al. Immunobiology of Crimean-Congo hemorrhagic fever. Antiviral Res. 199, 105244, 2022. DOI: 10.1016/j.antiviral.2022.105244
4. Roney M., Mohd Aluwi M.F.F. The importance of in silico studies in drug discovery. Intell. Pharm. 2(4), 578–579, 2024. DOI: 10.1016/j.ipha.2024.01.010
5. Scholte F.E.M., Spengler J.R., Welch S.R., Harmon J.R., Coleman-McCray J.D., Davies K.A., et al. Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model. Virus Res. 345, 199398, 2024. DOI: 10.1016/j.virusres.2024.199398
6. Clasman J.R., Everett R.K., Srinivasan K., Mesecar A.D. Decoupling deISGylating and deubiquitinating activities of the MERS virus papain-like protease. Antiviral Res. 174, 104661, 2020. DOI: 10.1016/j.antiviral.2019.104661
7. Tian W.J., Wang X.J. Broad-spectrum antivirals derived from natural products. Viruses 15(5), 1100, 2023. DOI: 10.3390/v15051100
8. Fakih T.M. Natural compounds activities against SARS-CoV-2 Mpro through bioinformatics approaches for development of antivirus candidates. J. Kim. Sains dan Apl. 24(5), 170–176, 2021. DOI: 10.14710/jksa.24.5.170-176
