Structure Based Virtual Screening and Molecular Docking Studies for Identification of Allosteric Inhibitors against Zika Virus Protease NS2B-NS3
Structure Based Virtual Screening and Molecular Docking Studies for Identification of Allosteric Inhibitors against Zika Virus Protease NS2B-NS3
Musrrat Fatima, Muhammad Saad Khan, Hamid Rashid, Asim Mehmood, Sumaira Kanwal, Muhammad Asif Rasheed and Farrukh Jamil*
ABSTRACT
Zika virus (ZIKV) has gained research interests after its recent outbreak in Brazil and America in 2015, where it affected millions of people. Studies have shown its role in developing microcephaly and GBS Syndrome. There is a need to develop drugs against ZIKV. Here we uses pharmacoinformatics techniques to identify potential inhibitors against ZIKV protease NS2B-NS3, which has a well-known role in the viral replication. By using three dimensional structure of the NS2B-NS3, an allosteric site has been identified in the protein. Moreover, the identified site is used for structure-based virtual screening. After screening 100,000 compounds, 14 compounds are selected, which fulfilled different already established drug likeliness parameters such as rule of five and nontoxic nature. These 14 compounds are used for pharmacophore modeling, and Zinc natural compounds database (ZND) is screened against the developed pharmacophore. The compounds with the highest pharmacophore fit scores are screened and docked on the identified allosteric site of NS2B-NS3. Analysis of the data showed two compounds (ZINC00845171, ZINC08782519)as potential inhibitors for NS2B-NS3 of ZIKV.
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October 2018
Vol. 50, Iss. 5, Pages 1601-1998
