Identification and Molecular Dynamic Simulation of Flavonoids from Mediterranean species of Oregano against the Zika NS2B-NS3 Protease

TL;DR

This study identifies flavonoids from Mediterranean oregano as potential inhibitors of Zika virus protease, highlighting Cirsiliol as a promising compound through molecular docking and dynamic simulations.

Contribution

The paper reports the first computational screening of oregano flavonoids against Zika NS2B-NS3 protease, identifying Cirsiliol as a potential therapeutic candidate.

Findings

Cirsiliol showed the highest binding affinity of -8.5 kcal/mol.

Cirsiliol demonstrated good stability in 100 ns MD simulation.

The study suggests Cirsiliol for further in vitro and in vivo testing.

Abstract

The Zika virus, is an emerging infectious disease causing severe complications such as microcephaly in infants and Guillain Barre syndrome in adults. There is no licensed vaccination or approved medicine to treat ZIKV infection. Therefore, extensive research is being carried out to find compounds that can be used effectively as therapeutic molecules to treat ZIKV infection. Oregano, a commonly found herb in the Mediterranean region, has been used predominantly for culinary purposes. The fact that the members of the Origanum species are a storehouse of various bioactive compounds gives us a solid reason to study compounds extracted from it for therapeutic purposes. In this study, were retrieved 20 Flavonoids found in various Origanum species belonging to the Mediterranean region from the PubChem database and pharmacological analysis using SwissADME and Molecular docking using AutoDock Vina 4.0. were carried out against the NS2B NS3 protease since it serves as an effective drug target owing to its role in viral replication and immune evasion within the host. The best hit compounds were subjected to MD simulation at 100 ns using Desmond Schrodinger to analyze the molecule's stability. We observed Cirsiliol as the best hit compound against the NS2B NS3 complex with a binding affinity of -8.5 kcal per mol. It also showed good stability during MD simulation. We recommend the use of Cirsiliol for in vitro and in vivo studies for further investigation concerning the ZIKA virus.