Targeting the omicron variant of SARS-CoV-2 with phytochemicals from Saudi medicinal plants: molecular docking combined with molecular dynamics investigations
Lina Eltaib, Abdulrahim A. Alzain
Abstract
The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered in November 2021, the omicron variant is more transmissible and is able to evade the immune system better than other previously identified SARS-CoV-2 variants, leading to a spike in cases. Great efforts have been made to discover inhibitors against SARS-CoV-2. Main protease (Mpro) inhibitors are considered promising anti-SARS-CoV-2 agents. The U.S. FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir is the first orally bioavailable inhibitor of SARS-CoV-2 Mpro. There is an urgent need to monitor the mutations and solve the problem of resistance, especially omicron Mpro, which contains one mutation - P132H. In the present study, 132,57 phytochemicals from 80 medicinal plants grown in Saudi Arabia were docked into the active site of Mpro omicron variant. Free binding energies were also calculated. This led to the discovery of five phytochemicals that showed better docking scores than the bound ligand nirmatrelvir. In addition, these molecules exhibited favorable free binding energies. The stability of compounds 1-5 with the protein was studied using molecular dynamics (MD) simulations. These compounds showed acceptable ADMET properties. The results were compared with the wild type. These candidates could be envisioned as new hits against SARS-CoV-2.Communicated by Ramaswamy H. Sarma