PMID:
J Biomol Struct Dyn. 2019 Oct 24:1-16. Epub 2019 Oct 24. PMID: 31595837
Abstract Title:
The identification of active compounds inextract inhibiting dengue virus serine protease and its computational studies.
Abstract:
The number of global dengue incidences is alarmingly high in recent years. The global distribution of four dengue serotypes has also added economic burden in the dengue-endemic countries. To discover the potent dengue virus inhibitors in the antler form of(Lingzhi or Reishi), the water extraction of normaland its antler form were conducted and the chemical compounds were identified by LC-MS. Six distinct chemical compounds identified in high abundance were hesperetin, thymidine, lucidenic acid, 11-aminoundecanoic acid, 5-carboxyvanillic acid and ganocin B. The water extracts ofin its antler form inhibited the DENV2 NS2B-NS3 protease activity at 84.6 ± 0.7%, higher than the normal. Then, molecular docking was performed on the homology model built from an in-house sequence. Docking simulation results showed that hesperetin and ganocin B were the best leads to bind at the catalytic triad of DENV2 NS2B-NS3pro via hydrogen bonding, van der Waals and pi-pi interactions. Extensive overlapping of HOMO-LUMO orbitals at the ringed regions of hesperetin helped to facilitate the entry of ligand to the catalytic triad cleft. LC-MS, molecular docking and density functional theory analyses confirmed that hesperetin was the strongest inhibitor against NS2B-NS3 protease. Communicated by Ramaswamy H. Sarma.
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