An Insight into Decoding Drug-resistant Key Proteins, in-silico TargetingApproach and Various Inhibitory Therapeutics of Hepatitis C Virus: ASystematic Review

Introduction: Hepatitis C virus (HCV) is believed to cause 130–170 million infections worldwide, or roughly 3% population worldwide, and poses a serious risk to global health. Hepatitis C is an enveloped +ve RNA virus belonging to the family Flaviviridae. All around the world, HCV infection is the main cause of serious liver diseases such as cirrhosis and hepatocellular carcinoma. Even though drugs have been around for a while, only a small number of them have been proven to be effective against every HCV genotype because of their genetic diversity and complexity. The objective of the paper to understand various protein targets of HCV and study various inhibitors from different sources and their scope in the treatment of HCV infection. Methods: The terms "core proteins," "structural and non-structural HCV proteins," "treatment strategies of HCV," and "hepatitis C virus" were used to search the scientific database for relevant publications. A selection of reports from PubMed, MEDLINE, Scopus, Web of Science, followed by Science Direct, and Google Scholar that were searched through 2024 are included in this review. In this work, the findings were evaluated, collected, and presented. There were 218 papers in all, and the number of articles published between 2010 and 2024 increased exponentially. Results: This study provides an overview of what is currently known about the virology, transmission, diagnosis, and treatment of HCV. Additionally, it offers a thorough examination of HCV proteins as potential targets for the creation of vaccines and antiviral medications. The NS5B polymerase, NS3/4A protease, entrance receptors, including CD81, and core proteins are among the specific HCV proteins that have been suggested as possible therapeutic targets. Additionally, the potential uses of HCV proteins as prognostic and diagnostic biomarkers. Although successful, the current direct- acting antiviral treatments have drawbacks related to resistance, genotype specificity, and cost. In order to guide future research on better preventive, diagnostic, and therapeutic approaches against this worldwide infectious disease threat, this review attempts to compile crucial knowledge on HCV biology and pathogenesis. Discussion: The findings of the review indicate the importance of understanding various protein targets of HCV and studying various inhibitors from different sources and their scope in the treatment of HCV infection. In support of the review, an in-silico based meta-analysis study is included to infer the complete antiviral potential of Hepatitis C Virus- Drug Resistance and different proteinsbased therapeutic targets. Conclusion: We intended to highlight the advances gained in managing and preventing HCV infection, as well as the ongoing challenges to HCV prevention. The primary goal was to connect with global health objectives in order to reduce the burden of chronic hepatitis, ultimately eliminating it as a public health hazard in the near future. The PROSPERO registration number for systematic review is 1080028.