To Explore the Potential Targets and Current Structure-based Design Strategies Utilizing Co-crystallized Ligand to Combat HCV

Abstract

Background: Hepatitis C Virus (HCV) belongs to the Hepacivirus family. HCV has been designated as a very dreadful virus as it can attack the liver causing inflammation and even may lead to cancer in chronic condition. It was es- timated that 71 million people around the world have chronic HCV infection. World Health Organization (WHO) reported that about 399000 people died because of chronic cirrhosis and liver cancer globally. In spite of abundance of availability of drugs for the treatment of HCV, however, the issue of drug resistance surpasses all the possibilities of therapeutic man- agement of HCV. Therefore, to address this issue of ‘drug-resistance’ various HCV targets were explored to quest the evaluation of the mechanism of the disease progression. Methods: An attempt has been made in the present study to explore the various targets of HCV involved in the mecha- nism(s) of the disease initiation and progression and to focus on the mode of binding of ligands, which are co-crystallized at the active cavity of different HCV targets. Conclusion: The present study could predict some crucial features of these ligands which possibly interacted with various amino acid residues responsible for their biological activity and molecular signaling pathway(s). Such binding mode may be considered as a template for the high throughput screening and designing of active congeneric ligands to combat HCV.

Trapping a non-cognate nucleotide upon initial binding for replication fidelity control in SARS-CoV-2 RNA dependent RNA polymerase

“…The SARS-CoV-2 virus responsible for the COVID-19 pandemic continues to evolve 1 and pose a threat to human life. 2 While much of the drug development besides successful vaccines has been focused on targeting the viral spike protein [3][4][5][6] or the main protease, [7][8][9][10] there are significant challenges remaining. The spike protein is known for its high variability 1,11,12 and the protease 13 can also mutate, becoming resistant to drugs, e.g., as seen in Hepatitis C virus (HCV).…”