In silico identification of potential allosteric inhibitors of the SARS-CoV-2 helicase

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic ravages the globe causing unprecedented health and economic challenges. As the world prospects for a cure, scientists are looking critically at strategic protein targets within the SARS-CoV-2 that have therapeutic significance. The Helicase is one of such targets and it is an enzyme that affects all facets of the SARS-CoV-2 RNA metabolism. This study is aimed at identifying small molecules from natural products that have strong binding affinity with and exhibit inhibitory activity against an allosteric site (Pocket 26) on the SARS-CoV-2 Helicase. The molecular docking simulations of SARS-CoV-2 Helicase (QHD43415-12.pdb) against a library of small molecules obtained from edible African plants was executed using PyRx. Triphenylmethane, which had a docking score of-7.4 kcal/mol on SARS CoV-2 Helicase was chosen as a reference compound. Based on the molecular descriptors of the compounds as provided by PubChem, a virtual screening for oral bioavailability was performed. Further screening for molar refractivity, pharmacokinetic properties, and bioactivity were performed using SwissADME, pkCSM, and Molinspiration webservers respectively. Molecular dynamic simulation and analyses were performed using the Galaxy webserver which uses the GROMACS software. The lead compounds are Gibberellin A12, A20, and A51 obtained from Green peas and the Okra plant. Gibberellin A20 and A51 were predicted to perform better than the standard and Gibberellin A51 showed the greatest inhibitory activity against SARS-CoV-2 Helicase. © 2021 Rowaiye et al and the authors.