Insights from computational studies on the potential of natural compounds as inhibitors against SARS-CoV-2 spike omicron variant

ABSTRACT Coronavirus disease 2019 (COVID-19) is a major global health emergency, with more than six million deaths worldwide. It is becoming increasingly challenging to treat COVID-19 due to the emergence of novel variants. The omicron variant is capable to evade defences and spread quickly. Among many validated COVID-19 targets, the spike (S) protein plays an important role in receptor recognition (via the S1 subunit) and membrane fusion (via the S2 subunit). The S protein is one of the vital targets for the development of drugs to combat this illness. In this research, we applied various computational methods such as molecular docking, molecular dynamics, MM-GBSA calculations, and ADMET prediction to identify potential natural products from Saudi medicinal plants against the spike omicron variant. As a result, three compounds (LTS0002490, LTS0117007, and LTS0217912) were identified with better binding affinity to the spike omicron variant compared to the reference compound (VE607). In addition, these compounds showed stable interactions with the target during molecular dynamics simulations for 140 ns. Last, these compounds have optimal ADMET properties. We suggest that these compounds may be considered promising hits to treat COVID-19 if experimentally validated.