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In silico identification of potential allosteric inhibitors of the SARS-CoV-2 Helicase.pdf (1.4 MB)
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In Silico Identification of Potential Allosteric Inhibitors of the SARS-CoV-2 Helicase

preprint
revised on 29.06.2020 and posted on 30.06.2020 by Adekunle Rowaiye, Olukemi Onuh, Titilayo Asala, Amoge Ogu, Doofan Bur, Ezinne Nwankwo, Uchenna Orji, Zainab Ibrahim, Jamila Hamza, Adaku Ugorji

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.

History

Email Address of Submitting Author

adekunlerowaiye@gmail.com

Institution

National Biotechnology Development Agency, Abuja

Country

Nigeria

ORCID For Submitting Author

0000-0002-8773-5944

Declaration of Conflict of Interest

No conflict of interest

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