We have located links that may give you full text access.
Inhibitory mechanism of 5-bromo-3-indoleacetic acid for non-structural-3 helicase hepatitis C virus with dynamics correlation network analysis.
Computational Biology and Chemistry 2018 October 10
Hepatitis C virus, Nonstructural 3 helicase (NS3h) protein is a well-studied segment of Non-structural 3/4 A helicase-protease protein that is crucial for the RNA duplex unwinding and RNA translocation during the process of HCV replication. Similar to other HCV nonstructural proteins, helicase is a potential target for antiviral drugs and several antiviral molecules have been used to target the RNA-binding cleft, despite the fact that none of those helicase antivirals have advanced the clinical trials. Compound 2t9 (5-bromo-1H-indol-3-yl acetic acid) has been identified through the integrated strategies and considered as a potential lead compound for the inactivation of HCV helicase. This inhibitor bind to the 3´-terminal RNA-binding cleft, and reduced the RNA binding and unwinding activity of the targeted protein. In the current study, using all-atom molecular dynamic simulation and correlations network strategy, we scrutinized the inhibitory mechanism of compound 2t9 that needs to be elucidated for the improvement of indole-based and similar HCV helicase inhibitors. Consequently, by comparing the structural dynamics of free (NS3hWT ) and bound (NS3h/2t9WT ) protein, we identified that the inhibitor-bound protein achieved a conformation resemblance to the open conformation, where the RNA is displaced results in destabilization of RNA-binding cleft, disruption in ATP/ADP binding site and alter the inter-domain communication. The results were evaluated by using the W501 L mutated system. The information based on detailed dynamic aspects of the drug targeted protein will facilitate the researchers in the development of HCV antiviral drugs.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app