1Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
American Journal of Microbiological Research.
2015,
Vol. 3 No. 6, 201-205
DOI: 10.12691/ajmr-3-6-5
Copyright © 2015 Science and Education PublishingCite this paper: Satheesh Natarajan, Rohana Binti Yusuf. A Small Molecule Inhibitor of Serine Protease Inhibits the Replication of Flavivirus in Vitro.
American Journal of Microbiological Research. 2015; 3(6):201-205. doi: 10.12691/ajmr-3-6-5.
Correspondence to: Satheesh Natarajan, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Email:
satheesh.sahana@gmail.comAbstract
Flavivirus plays a significantly in human disease and mortality. The N-terminal domain of the flaviviral nonstructural NS3 protein codes for the serine, chymotrypsin fold proteinase NS3pro. The cofactor encoded by the upstream gene in the genome nonstructural NS2Bis essential for proteolytic activity of NS3pro. The processing and replication of the flaviviral polyprotein was exhibited by the two-component NS2B-NS3pro, this makes NS2B-NS3pro a promising target for anti-flavivirus drugs because of its essential function in the posttranslational processing of the viral polyprotein precursor. Based on the above hypothesis we identified and synthesized some anti viral compounds. (1’R, 2’S, 6’R)-2-hydroxy 4, 6-dimethoxyisopanduratin A 4 was synthesized in 38 % yield from commercially available products over three steps. Together with its precursor 2, 4, 6-trimethoxyisopanduratin A 3, both of these compounds showed promising competitive inhibitory activities towards dengue 2 virus NS3 protease with the Ki values of 39.68 and 19.84 µM, respectively. The starting materials β-trans-ocimene showed competitive inhibitory activities, but 2’, 4’, 6’-trimethoxychalcone was observed to be non-competitive.
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