Document Type : Article
Author
Department of Biology, Payame Noor University, Tehran, Iran
10.30473/eab.2025.74787.1996
Abstract
Crimean-Congo Hemorrhagic Fever (CCHF) is a zoonotic viral disease with high mortality, for which no specific and effective treatment has yet been introduced. The causative virus, classified within the Nairovirus genus and Orthonairoviridae family, encodes a polyprotein via its L segment, which includes the RNA-dependent RNA polymerase (RdRp) and an N-terminal OTU protease domain. The OTU domain, through its deubiquitinase (DUB) activity, plays a role in suppressing the host immune response and, due to its relatively conserved sequence, represents a promising target for antiviral drug design. This study aimed to evaluate the inhibitory effect of the natural compound Phellopterin (Phe), derived from Heracleum persicum, on the OTU domain. The crystal structure of OTU (PDB ID: 3PRP) was prepared and subjected to molecular docking using AutoDock 4.0. The top-ranked complex was then analyzed via a 150-nanosecond molecular dynamics (MD) simulation using GROMACS. Phellopterin showed a favorable binding affinity (ΔG = –8.1 kcal/mol) and formed stable interactions with residues such as Ala79–Leu86 near the active-site entry. Analyses including RMSD, RMSF, Rg, hydrogen bonding, and PCA confirmed the structural stability of the complex. ADMET evaluation also indicated desirable pharmacokinetic properties, oral absorption, cellular permeability, and safety. Altogether, Phellopterin may serve as a potential inhibitor of the CCHFV OTU protease and provide a foundation for the development of effective natural antiviral agents.
Keywords
- Crimean-Congo Hemorrhagic Fever virus
- Furanocoumarins
- Molecular docking simulation
- Phellopterin
- RNA-dependent RNA polymerase
Main Subjects
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