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Drug repurposing and small molecule screening for phospholipase A2 inhibition in Naja species venoms: an integrated in silico and in vitro approach
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DOI：10.1080/15569543.2025.2591040.png)
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Abstract
En 中文
Envenoming by Naja species is of serious public health impact in Africa and phospholipase A2 (PLA2s) are of the primary enzymes causing fatalities in envenomed victims. This study identified promising inhibitors of the Phospholipase A2 (PLA2) enzyme from Naja species.
In this study, 1823 FDA-approved drugs, Catechin and Varespladib were docked against the PLA2 enzyme from Naja sp. venoms with PyRx software and visualized using BIOVIA Discovery Studio. The ADMET properties was determined using AdmetLab 3.0. The inhibitory potential of three out of the eight promising inhibitors, including paliperidone, bexarotene, and mizolastine, alongside Catechin and EchiTab-PLUS (control), were tested against isolated PLA2 from Naja nigricollis, Naja haje, and Naja melanoleuca venoms as a single agent and in combination at concentrations of 0.1 mM and 0.05 mM.
Molecular docking results indicate that paliperidone had the lowest binding affinity score of -9.7 kcal/mol compared to Varespladib and Catechin which had -7.0 and -6.7 kcal/mol, respectively. The ADMET analysis indicated that all the promising inhibitors are likely to be orally bioavailable, with Catechin being the safest and most easily metabolized. The in vitro study revealed that Catechin exhibited considerable inhibitory activity against the PLA2 enzyme. Catechin at 0.1 mM, showed the highest inhibition of 52%, 44%, and 33% against the PLA2 enzyme from N. nigricollis, N. haje, and N. melanoleuca venoms, respectively. Findings indicate that Catechin is a promising and safe inhibitor candidate of the PLA2 enzyme in Naja spp. Venoms.
Keywords:
ADMET profiling
catechin
computational drug discovery
drug repurposing
FDA-approved drugs
molecular docking
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