Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations
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...
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| Format: | Article |
| Language: | English |
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Springer
2020-12-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016420302401 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Noreen |
| collection | DOAJ |
| description | 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 (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. |
| format | Article |
| id | doaj-art-0ae3feeae3084428a93ef05b0b59c378 |
| institution | Kabale University |
| issn | 1319-0164 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj-art-0ae3feeae3084428a93ef05b0b59c3782025-08-20T03:54:28ZengSpringerSaudi Pharmaceutical Journal1319-01642020-12-0128121580159110.1016/j.jsps.2020.10.005Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations Noreen0Roshan Ali1Syed Lal Badshah2Muhammad Faheem3Sumra Wajid Abbasi4Riaz Ullah5Ahmed Bari6Syed Babar Jamal7Hafiz Majid Mahmood8Adnan Haider9Sajjad Haider10Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan; Department of Chemistry, Islamia College University, Peshawar, Pakistan; Corresponding author at: Department of Chemistry, Islamia College University, Peshawar, Pakistan. Tel.: +92-346-971-3604.Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, PakistanDepartment of Chemistry, Islamia College University, Peshawar, PakistanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi, PakistanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi, PakistanDepartment of Pharmacognosy (MAPPRC), College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmacuitcal Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi, PakistanDepartment of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi, PakistanDepartment of Chemical Engineering, College of Engineering, King Saud University, Riyadh, Saudi ArabiaZika 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 (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.http://www.sciencedirect.com/science/article/pii/S1319016420302401Zika virusNS5 RNA-dependent RNA polymeraseVirtual screeningDocking studiesMolecular dynamicsBinding free energy |
| spellingShingle | 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 Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations Saudi Pharmaceutical Journal Zika virus NS5 RNA-dependent RNA polymerase Virtual screening Docking studies Molecular dynamics Binding free energy |
| title | Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations |
| title_full | Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations |
| title_fullStr | Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations |
| title_full_unstemmed | Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations |
| title_short | Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations |
| title_sort | identification of potential inhibitors of zika virus ns5 rna dependent rna polymerase through virtual screening and molecular dynamic simulations |
| topic | Zika virus NS5 RNA-dependent RNA polymerase Virtual screening Docking studies Molecular dynamics Binding free energy |
| url | http://www.sciencedirect.com/science/article/pii/S1319016420302401 |
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