Molecular docking and pharmacokinetics analysis of phytochemicals from Piper caninum as dengue NS2B-NS3 protease inhibitors

Abstract

Dengue fever affects 390 million people each year. Currently, there is no specific medicine to treat this disease. Thus, the search for potential NS2B-NS3 protease in-hibitors has attracted increasing research interest. The dengue protease NS2B-NS3 was used as a molecular target because of its vital function in viral replication. Piper caninum belongs to the Piperaceae family, found inhabited in Malaysia and Indone-sia. This plant possesses various phytochemicals with various health benefits. How-ever, the anti-dengue activity of this plant is yet to be discovered. Therefore, the objective of this research is to evaluate the inhibitory activity of phytochemicals from P. caninum against NS2B-NS3 using in silico experimentation. Molecular docking using AutoDock Vina was utilized to identify the binding interaction of phytochem-icals on NS2B-NS3. SwissADME and ProTox-II web servers were used to analyse the ADMET (absorption, distribution, metabolism, excretion, and toxicity) of the phytochemicals. Results showed that cepharadione A, bornyl caffeate, and (+)-bornyl p-coumarate had comparable molecular interaction with the reference com-pound, curcumin. Analysis of in silico pharmacokinetics properties revealed that these phytochemicals have good pharmacokinetics profiles and excellent drug-abil-ity, which obeyed Lipinski’s Rule of Five. This study shows the potential inhibitory activity of the phytochemicals against NS2B-NS3 for a lead in the development of dengue inhibitors.