AI Article Synopsis

  • Hepatitis C Virus (HCV) poses a major health threat globally, often leading to severe liver diseases like cirrhosis, due to its rapidly changing genome driven by NS5B polymerase.
  • This study investigates marine bacteria-derived compounds that can potentially inhibit the HCV NS5B polymerase through virtual screening, focusing on their binding affinity and stability.
  • Four compounds emerged as top candidates after extensive analysis, and their strong binding to NS5B shows promise for further experimental testing as potential treatments against HCV.

Article Abstract

Hepatitis C Virus (HCV) is a significant health concern affecting a large portion of the global population and is a major cause of acute liver diseases, including cirrhosis. The variability in the HCV genome mainly results from the rapid replication facilitated by the NS5B polymerase, making it a prime target for anti-HCV drug development. This study explores potential compounds from marine bacteria that could inhibit the HCV NS5B polymerase by virtual screening, analyzing the energetics, and dynamic behavior of target-compound complexes. Virtual screening with the Lipinski filter was employed to select compounds from the marine bacteria database that demonstrated strong binding affinity to NS5B. The top four (CMNPD27216, CMNPD21066, CMNPD21065, and CMNPD27283) compounds, ranked by their re-docking scores, underwent additional evaluation. Molecular dynamics simulations for 200 ns were conducted to assess the dynamic stability of these complexes in a solvent environment. Furthermore, methods such as MM-GBSA, PCA, and free energy landscape analysis were used to analyze the system's energetics and identify stable conformations by locating transition states. The findings suggest that these compounds exhibit promising binding capabilities to HCV polymerase and could be considered for future experimental validation.

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Source
http://dx.doi.org/10.1007/s11030-024-10904-xDOI Listing

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