Computer-aided drug design against spike glycoprotein of SARS-CoV-2 to aid COVID-19 treatment
Fecha
2020Autor
Shehroz, Muhammad
Zaheer, Tahreem
Hussain, Tanveer
Resumen
Background: SARS-CoV-2 has the Spike glycoprotein (S) which is crucial in attachment with host receptor and cell
entry leading to COVID-19 infection. The current study was conducted to explore drugs against Receptor Binding
Domain (RBD) of SARS-CoV-2 using in silico pharmacophore modelling and virtual screening approach to combat
COVID-19.
Methods: All the available sequences of RBD in NCBI were retrieved and multiple aligned to get insight into its
diversity. The 3D structure of RBD was modelled and the conserved region was used as a template to design
pharmacophore using LigandScout. Lead compounds were screened using Cambridge, Drugbank, ZINC and
TIMBLE databases and these identified lead compounds were screened for their toxicity and Lipinski's rule of five.
Molecular docking of shortlisted lead compounds was performed using AutoDock Vina and interacting residues
were visualized.
Results: Active residues of Receptor Binding Motif (RBM) in S, involved in interaction with receptor, were found to
be conserved in all 483 sequences. Using this RBM motif as a pharmacophore a total of 1327 lead compounds
were predicted initially from all databases, however, only eight molecules fit the criteria for safe oral drugs.
Conclusion: The RBM region of S interacts with Angiotensin Converting Enzyme 2 (ACE2) receptor and Glucose
Regulated Protein 78 (GRP78) to mediate viral entry. Based on in silico analysis, the lead compounds scrutinized
herewith interact with S, hence, can prevent its internalization in cell using ACE2 and GRP78 receptor.
The compounds predicted in this study are based on rigorous computational analysis and the evaluation of
predicted lead compounds can be promising in experimental studies.
Palabras clave
Bioinformatics; Immunology; Computer-aided drug design; Drug binding; Infectious disease; Viral protein; Viruses; SARS-CoV-2; Receptor binding domain; Virtual screening; Lead compounds; Anti-Viral drugs; COVID-19Enlace al recurso
https://doi.org/10.1016/j.heliyon.2020.e05278Colecciones
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