American Journal of Microbiological Research
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American Journal of Microbiological Research. 2015, 3(6), 201-205
DOI: 10.12691/ajmr-3-6-5
Open AccessArticle

A Small Molecule Inhibitor of Serine Protease Inhibits the Replication of Flavivirus in Vitro

Satheesh Natarajan1, and Rohana Binti Yusuf1

1Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Pub. Date: December 04, 2015

Cite this paper:
Satheesh Natarajan and 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


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.

flavivirus NS2B/NS3pro serine protease small molecule compounds

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