Post Date
Oct 10 2024

Identification of New Potential Inhibitors of Hepatitis C Virus (HCV) and SARS-CoV-2 Replication

Year
2024
Supervisor:
Dr. Syed Shahzad Ul Hussan
Students:
Hafsa Iftikhar
MS/PhD
PhD

Abstract:

 Hepatitis C virus (HCV) infections are the leading cause of liver cancer all around the world. Due to rapidly evolving nature of this virus, it develops resistance against effective drugs. Although many officious treatment regimens are available, resistance against every currently used drug has been reported that is increasing gradually. Therefore, there is a need of continuous effort to discover new antiviral agents especially in the absence of an effective vaccine. Non-structural protein 5A (NS5A) of HCV plays essential roles in viral replication cycle particularly in genomic replication, viral particle assembly and host immune modulation. Moreover, there is no homologue of this protein in human that makes it an important target for therapeutic interventions. This study aimed to discover new inhibitors of NS5A of HCV genotype 3a and its drug resistant variant, which is the most prevalent genotype in Pakistan. We used two parallel approaches, in silico screening and biophysical high throughput screening to identify potential inhibitors, which were validated in two cell cultures-based assays, replicon and HCVcc assay. In this regard we identified and validated three new inhibitors of HCV NS5a which not only inhibit replication of wild-type virus but also inhibit drug resistant variants. Moreover, in the second project of PhD during the early days of COVID-19 pandemic we used computational approach to study the interactions of already know drugs and drug like molecules with three different proteins of SARS-CoV2 with aim to create knowledge for drug re-purposing. Publications:

 1. Shami, A. A., Akhtar, M. T., Mumtaz, M. W., Mukhtar, H., Tahir, A., Shahzad-ul-Hussan, S., Chaudhary, S, U., Muneer, B., Iftikhar, H., & Neophytou, M. (2023). NMR-Based Metabolomics: A New Paradigm to Unravel Defense-Related Metabolites in Insect-Resistant Cotton Variety through Different Multivariate Data Analysis Approaches. Molecules, 28(4), 1763. 

2. Iftikhar, H., Maqsooq, U., Tariq, R., & Arif, M. (2021). Diversity analysis of USDA Mini-core panel of rice germplasm using Biochemical and waxy gene linked DNA markers. Journal Plantarum, 3(2)-04 25-43. 

3. Iftikhar, H., Ali, H. N., Farooq, S., Naveed, H., & Shahzad-ul-Hussan, S. (2020). Identification of potential inhibitors ofthree key enzymes of SARS-CoV2 using computational approach. Computers in Biology and Medicine, 122,1038