Pharmacophore based virtual screening for natural product database revealed possible inhibitors for SARS-COV-2 main protease.

The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.

Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study.

The COVID-19 pandemic has urged for the repurposing of existing drugs for rapid management and treatment. Renin inhibitors down regulation of ACE2, which is an essential receptor for SARS-CoV-2 infection that is responsible for COVID-19, in addition to their ability to act as protease inhibitors were encouraging aspects for their investigation as possible inhibitors of main protease of SARS-CoV-2 via computational studies. A Pharmacophore model was generated using the newly released SARS-COV-2 main protease inhibitors. Virtual screening was performed on renin inhibitors, and Drug likeness filter identified remikiren and 0IU as hits. Molecular docking for both compounds showed that the orally active renin inhibitor remikiren (Ro 42-5892) of Hoffmann-La Roche exhibited good molecular interaction with Cys145 and His41 in the catalytic site of SARS-CoV-2 main protease. Molecular dynamics simulation suggested that the drug is stable in the active site of the enzyme.