Molecular mechanism of virgin coconut oil as a Nsp-3 inhibitor of SARS-CoV-2

Abstract

Virgin coconut oil (VCO) is a natural product that contains mostly medium-chain lipids, such as palmitates, stearates, and oleates. This study aims to explore whether VCO would make an effective to Nsp3b as one of target for virtual ligand screening of potential drug targets inhibitor of SARS-CoV-2, especially medium-chain content. In this study, computational investigations (in silico) were conducted using five long-chain molecules constituting VCO, namely palmitate, myristate, stearate, laurate, and oleate. Molecular docking simulation was conducted using the PLANTS 1.1. The binding affinity results revealed palmitate, and stearate have lower score than the co-crystalize ligand of Nsp3. Stearate and palmitate binding affinity score were -6.45 and -6.23 respectively, while co-crystalize ligand as our ligand control is -5.71, despite co-crystalize ligand hydrogen bonds is more than both of palmitate and stearate. In addition to molecular docking, we perform molecular dynamic simulation and found stearate relatively stable to bind Nsp3. The RMSD of complex protein to stearate was stable below 1 nm over 20 ns simulation. This could be caused by hydrogen bonds between stearate and Nsp3 protein, where average of hydrogen bond is 1.2, and recorded to be higher during the last 10 ns with an average of 1.5. Both palmitate and stearate also found have biological activity against several virus including adenovirus, poxvirus, and influenza virus with score greater than 0.5 (score from 0 to 1).