Sivasothy Y, Liew S Y, Othman M A, Abdul Wahab S M, Hariono M, Mohd Nawi M S, Abdul Wahab H, Awang K
School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Selangor, Malaysia.
Chemistry Division, Centre for Foundation Studies in Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
Trop Biomed. 2021 Jun 1;38(2):79-84. doi: 10.47665/tb.38.2.044.
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 μM) and potent (7.55 ± 1.64 μM) 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 π-π 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.
NS2B/NS3蛋白酶对登革病毒的发病机制至关重要。因此，抑制这种蛋白酶被认为是开发新型抗病毒药物的关键策略。在本研究中，从锡兰肉豆蔻果实中分离得到的酰基酚类化合物马拉巴酮C（3）和E（4），分别被鉴定为中等活性（27.33±5.45μM）和强效活性（7.55±1.64μM）的登革病毒2型NS2B/NS3蛋白酶抑制剂，这也是关于酰基酚类化合物对登革病毒2型NS2B/NS3蛋白酶抑制活性的首次报道。基于分子对接研究，化合物3和4均与Tyr161存在π-π相互作用。化合物3与Gly151、Gly153和Tyr161存在氢键相互作用，而化合物4则与Ser135、Asp129、Phe130和Ile86形成氢键。本研究结果表明，马拉巴酮C（3）和E（4）可作为天然来源的新型登革热抗病毒药物开发的先导化合物。
