Repositioning of RdRp Inhibitors Against HCV NS5B Polymerase Utilizing Structure-Based Molecular Docking
1Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Kashipur-244713,India.
Insights
Drug repurposing identified potential Hepatitis C Virus (HCV) treatments. Structure-based docking screened existing inhibitors against HCV RNA-dependent RNA polymerase (RdRp), revealing promising candidates for further development.
Area of Science:
- Virology
- Drug Discovery
- Computational Chemistry
Background:
- Hepatitis C Virus (HCV) affects millions globally, causing cirrhosis and liver cancer.
- Existing HCV treatments face challenges with drug resistance and toxicity.
- Drug repurposing offers an economical strategy to identify novel anti-HCV therapies.
Purpose of the Study:
- To identify potential drug candidates for Hepatitis C Virus (HCV) by repurposing inhibitors of RNA-dependent RNA polymerase (RdRp).
- To evaluate the binding affinity and interaction modes of existing RdRp inhibitors against the HCV NS5B polymerase using molecular docking.
Main Methods:
- Structure-based molecular docking simulations were employed.
- Eighty-seven compounds with inhibitory activity against Dengue virus (DENV), Zika virus (ZIKV), and Yellow fever virus (YFV) RdRp were screened.
- Interactions were compared against sofosbuvir diphosphate, a known HCV RdRp inhibitor.
Main Results:
- Several compounds, including N-sulfonylanthranilic acid derivative (6), R1479 (17), DMB220 (20), FD-83-KI26 (23), CCG-7648 (40), T-1106 (50), mycophenolic acid (65), and DMB213 (69), showed significant binding affinity.
- These compounds exhibited docking scores ranging from -7.602 to -8.971 Kcal/Mol.
- The binding modes of these compounds closely resembled that of the reference drug.
Conclusions:
- The identified compounds demonstrate satisfactory affinity for the Hepatitis C Virus RdRp.
- These compounds represent potential leads for developing new anti-HCV therapies.
- Structure-based drug repurposing is a cost-effective method for screening anti-HCV drug candidates.
Objective:
Hepatitis C Virus (HCV) is very dreadful as it can attack an estimated 71 million people around the world. The World Health Organization (WHO) reported that every year about 399000 people die due to HCV caused by chronic cirrhosis and liver cancer globally. There are many drugs available for the treatment of HCV. But drug resistance and toxicity are major issues. The quest for potential drugs utilizing repositioning would be a very useful and economical method to combat HCV.
Methods:
One of the most common HCV targets is RNA-dependent RNA polymerase (RdRp). The RdRp is common in HCV, Dengue virus (DENV), Zika virus (ZIKV), and Yellow fever virus (YFV) belonging to the same family of Flaviviridae. An attempt has been made in the present study to reposition different DENV, ZIKV, and YFV RdRp inhibitors against HCV NS5B polymerase utilizing structure-based molecular docking which explores the affinity and mode of binding of these RdRp inhibitors.
Results:
Several 87 compounds having dengue, yellow fever and zika RdRp inhibitory activities have been taken into consideration for the screening of potential RdRp leads utilizing docking simulation, which focuses on the affinity and mode of binding of sofosbuvir diphosphate, a standard HCV, RdRp inhibitor.
Conclusion:
The compounds 6 (N-sulfonylanthranilic acid derivative), 17 (R1479), 20 (DMB220), 23 (FD-83-KI26), 40 (CCG-7648), 50 (T-1106), 65 (mycophenolic acid), and 69 (DMB213) exhibited docking score within the range of -7.602 to -8.971 Kcal/Mol having almost same mode of interaction as compared to the reference drug molecule. The drugs mentioned above possess satisfactory affinity to bind the hepatitis C viral RdRp and thus may be used to treat the disease. Therefore, these predicted compounds may be potential leads for further testing of anti HCV activity and can be repurposed to combat HCV. The high throughput shotgun of drug repurposing utilizing structure-based docking simulation freeware would be a cost-effective way to screen the potential anti-HCV leads.
More Related Videos
06:03Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Related Concept Videos
01:30Inhibitors of Viral Protein Synthesis
01:22Antiviral Nucleoside Inhibitors