Metabolite Profiling and in vitro Evaluation of Lepisanthes fruticosa Fruit Pulp Extract as Inhibitor against Dengue and West Nile Virus NS2B-NS3 Proteases

Background: Dengue virus serotype 2 (DENV2) and West Nile virus (WNV) fevers are mosquito-borne diseases with no effective treatment at present In recent years, the development of plant-based antivirals targeting the viral NS2B-NS3 serine proteases has been the main focus as the synthetic antivirals available are not specific and less safe. Objectives: To evaluate the inhibitory activity of Lepisanthes fruticosa pulp extract against NS2B-NS3 proteases from DENV2 and WNV and identify the metabolites from this fruit extract. Materials and Methods: In vitro DENV2 and WNV NS2B-NS3 proteases assays were carried out using the methanolic extract of L. fruticosa pulp. Liquid chromatography-electron spray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) and gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS) were performed to determine the metabolites present in this fruit species extract. Results: L fruticosa extract exhibited inhibitory activity toward DENV2 and WNV NS2B-NS3 proteases with 50% inhibitory concentration value of 1.733 +/- 0.195 and 9.245 +/- 0.938 mg/mL, respectively. LC-ESI-MS/MS of L. fruticosa extract identified epigallocatechin-catechin, epigallocatechin, epicatechin, catechin, cyanidin rutinoside, procyanidin trimer, rutin, myricetin rhamnohexoside, luteolin glucoside and its derivative which were from the flavonoid group. In addition, GC-MS/MS identified fatty acids and sterols. Conclusion: The inhibitory activity of L. fruticosa pulp extract toward NS2B-NS3 proteases from DENV2 and WNV suggests this fruit species as a potential source for the development of antiviral. Metabolites from the groups of flavonols, flavones, and sterols identified in L fruticosa pulp may contribute to the inhibitory properties of L. fruticosa.

Automated summary

The inhibitory activity of Lepisanthes fruticosa pulp extract against NS2B-NS3 proteases from DENV2 and WNV suggests the potential of this fruit species for antiviral development. Metabolites from the groups of flavonols, flavones, and sterols in L. fruticosa pulp may contribute to its inhibitory properties.