Identification of Potential Inhibitors of Zika Virus NS5 RNA-Dependent RNA Polymerase Through Virtual Screening and Molecular Dynamic Simulations

Noreen, Roshan Ali, Syed Lal Badshah, Muhammad Faheem, Sumra Wajid Abbasi, Riaz Ullah, Ahmed Bari, Syed Babar Jamal, Hafiz Majid Mahmood, Adnan Haider, Sajjad Haider
2020 Saudi Pharmaceutical Journal  
Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of flaviviruses are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase
more » ... RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.
doi:10.1016/j.jsps.2020.10.005 pmid:33424251 pmcid:PMC7783101 fatcat:nglvkij33ncnde6ol4u3kbbtyi