A novel respiratory pathogen, SARS-CoV-2 has recently received worldwide
attention and has been declared a public health emergency of global
concern. Entry of SARS-CoV-2 is mediated through the viral spike
glycoprotein (S2). Afterwards, the virus gets hold of the host cell
machinery by employing the use of viral main protease 3CLpro and NSP15
endoribonuclease. In the present in silico study, active site mapping of
the viral virulence factors was rendered by means of DoG Site Scorer.
The possibility of repurposing of 2-deoxy-D-glucose (2-DG), a
radio-chemo-modifier drug used for optimizing cancer therapy, and one of
its derivative (1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose, has
been investigated by conducting ligand-receptor docking. Binding pose
depictions of ligands and viral receptors were assessed by employing
molecular dynamics analysis. Molinspiration and Toxicity Estimation
Software tools were used to assess the drug likeliness, bioactivity
indices and ADMETox values. 2-DG can dock efficiently with viral main
protease 3CLpro as well as NSP15 endoribonuclease, thus efficiently
inactivating these viral receptors leading to incapacitation of the
SARS-CoV-2 virus. Such incapacitation was possible by means of formation
of a hydrogen bond between 2-DG and proline residues of viral protease.
The 2-DG derivative formed a hydrogen bond with the glutamine amino acid
residues of the viral spike glycoprotein. The present in silico study
supports the potential benefits of using 2-DG and its glucopyranose
derivative as repurposed drugs/prodrugs for mitigating the novel
COVID-19 infection. Since both these moieties present no signs of
serious toxicity, further empirical studies on model systems and human
clinical trials to ascertain effective dose-response are warranted and
should be urgently initiated.
Glucose antimetabolite 2-Deoxy-D-Glucose and its derivative as promising candidates for tackling COVID-19: Insights derived from in silico docking and molecular simulations