In Silico Identification of Potential Allosteric Inhibitors of the SARS-CoV-2 Helicase
2020
The 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. One of such targets
is the Helicase which is an enzyme that affects all aspects of SARS-CoV-2 RNA
metabolism. The aim of this study is to identify small molecules from natural
products that have strong binding affinity with and inhibitory activity against
an allosteric site (Pocket 26) of SARS-CoV-2 Helicase. Pyrx was used for the in silico molecular docking simulations
of SARS-CoV-2 Helicase (QHD43415-12.pdb) against a library of small molecules
obtained from edible African plants. Triphenylmethane which had a docking score
of -7.4 kcal/mol was chosen as a reference molecule. Virtual screening for oral
bioavailability was done based on the molecular descriptors of the compounds as
provided by Pubchem. SwissADME, pkCSM, and Molinspiration were used for further
screening for molar refractivity, saturation, promiscuity, pharmacokinetic
properties, and bioactivity respectively. The Galaxy webserver which uses the
GROMACS software was used for the molecular dynamic simulation and analyses.
The lead compounds are Gibberellin A12, A20 and A51 obtained from Green peas
and the Okra plant. Gibberellin A20 and A51 performed
better than the standard. Gibberellin A51 is predicted to show the greatest
inhibitory activity against SARS-CoV-2 Helicase. It is recommended that the
inhibitory activities of the lead compounds be further investigated.
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