Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King
Document Type
Article
Publication Date
6-1-2021
Abstract
The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 +/- 5.45 mu M) and potent (7.55 +/- 1.64 mu M) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have pi-pi interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.
Keywords
Myristica cinnamomea King, Acylphenols, Malacaricone C, Malabaricone E, DENV-2 NS2B/NS3 protease
Divisions
foundation,Science
Funders
Universiti Malaya [Grant No: RP001-2012A/B & UM.C/625/1/HIR/MOHE/SC/37],Centre National de la Recherche Scientifique (CNRS) [Grant No: 57-02-03-1007]
Publication Title
Tropical Biomedicine
Volume
38
Issue
2
Publisher
Malaysian Soc Parasitology Tropical Medicine
Publisher Location
21-5-2, BLOCK, E, DIAMOND SQUARE, JALAN 3-50, OFF JALAN GOMBAK, KUALA LUMPUR, MALAYSIA