Targeting Crimean-Congo hemorrhagic fever virus: computational and MD-driven discovery of Moringa oleifera peptides against the RdRp-embedded OTU protease.

“Targeting Crimean-Congo hemorrhagic fever virus: computational and MD-driven discovery of Moringa oleifera peptides against the RdRp-embedded OTU protease. Hassam M(1), Rubina(2), Zheng H(3), Moin ST(2), Uddin R(4)(5). Author information: (1)Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. (2)Third World Center for Science and Technology H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. (3)School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. (4)Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. mriazuddin@iccs.edu. (5)Western Caspian University, Baku, Azerbaijan. mriazuddin@iccs.edu. Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne pathogen causes hemorrhagic disease with high fatality rates, and no approved vaccines/antivirals currently exist. The viral L protein contains a unique ovarian tumor (OTU) protease domain that cleaves ubiquitin and ubiquitin-like modifiers from host proteins, thereby aiding immune evasion and viral replication. Targeting the OTU domain represents a promising strategy for therapeutic intervention. Peptides obtained from Moringa oleifera proteome that mimic the binding mode of the endogenous ubiquitin molecule. These peptides were computationally screened for their ability to bind the OTU protease domain, incorporating both conventional cysteine protease inhibitors and protein-protein interaction interface mimetics. This study revealed Pep31 with a strong balance of binding affinity, solubility, and structural stability, highlighting its potential as a novel OTU protease inhibitor. While our findings are computational, they provide a foundation for experimental validation and the future development of peptide-based antivirals targeting CCHFV. © 2026. The Author(s). Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study did not involve any experiments with human participants, animals, or clinical data. All research was conducted using publicly available data, computational modeling, and in silico analyses. Therefore, ethical approval and informed consent were not required. The authors affirm that the research adheres to the ethical standards and guidelines of Scientific Reports. All authors have reviewed and approved the final manuscript and declare that the work is original and free from any conflicts of interest.”