Unraveling the Pathogenesis of Crimean-Congo Hemorrhagic Fever: A Novel Approach via Non-Targeted Metabolomics by NMR Spectroscopy

The application of metabolomics for studying modifications in host metabolism due to viral infections has proven to be a game-changing approach. Prior to our study, only one other ‘omics’ study has been carried out that investigates the interplay between the host and CCHFV and its subsequent pathogenesis. We employed NMR spectroscopy, given its advantages in terms of reproducibility, minimal sample preparation, and capability to analyze complex biofluids. Our methodology builds upon the proven success of metabolomics in the research of other viral hemorrhagic fevers such as Ebola, Marburg, and Dengue. Our research underlines the critical role of SAH, a metabolite involved in numerous biochemical reactions. We provide new insights into the metabolic alterations occurring in CCHF patients. These alterations not only shed light on the disease’s pathogenesis but also pave the way for potential biomarkers and therapeutic targets. Among all the metabolites detected, S-Adenosyl-L-homocysteine and Carnosine stood out as the most prevalent, warranting further exploration of their roles in CCHFV pathogenesis and their potential as therapeutic targets. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement CD acknowledges support from TUBITAK (Project No: 221S353). The authors acknowledge the use of the services and facilities of n2STAR-Koc University Nanofabrication and Nanocharacterization Center for Scientific and Technological Advanced Research. The authors gratefully acknowledge use of the services and facilities of the Koch University Is Bank Infectious Disease Center (KUIS-CID). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by Koç University Ethics Committee and all the procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee ethical standards. A written informed consent was obtained from all patients. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors