Research Paper
Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches

https://doi.org/10.1016/j.meegid.2020.104451Get rights and content

Highlights

  • The present study was designed to identify potential molecules against the structural proteins of SARS-CoV-2, responsible for envelope formation, virion assembly and pathogenesis.

  • The study identified rutin and doxycycline, as the most potent inhibitor of SARS-CoV-2 envelope (E) protein.

  • Caffeic acid and ferulic acid were found to inhibit SARS-CoV-2 membrane (M) protein.

  • While simeprevir and grazoprevir showed a high binding affinity for nucleocapsid (N) protein

  • The identified ligand showed excellent pharmacokinetic properties and the protein-ligand complexes were stable throughout MD simulation period.

Abstract

WHO has declared the outbreak of COVID-19 as a public health emergency of international concern. The ever-growing new cases have called for an urgent emergency for specific anti-COVID-19 drugs. Three structural proteins (Membrane, Envelope and Nucleocapsid protein) play an essential role in the assembly and formation of the infectious virion particles. Thus, the present study was designed to identify potential drug candidates from the unique collection of 548 anti-viral compounds (natural and synthetic anti-viral), which target SARS-CoV-2 structural proteins. High-end molecular docking analysis was performed to characterize the binding affinity of the selected drugs-the ligand, with the SARS-CoV-2 structural proteins, while high-level Simulation studies analyzed the stability of drug-protein interactions. The present study identified rutin, a bioflavonoid and the antibiotic, doxycycline, as the most potent inhibitor of SARS-CoV-2 envelope protein. Caffeic acid and ferulic acid were found to inhibit SARS-CoV-2 membrane protein while the anti-viral agent's simeprevir and grazoprevir showed a high binding affinity for nucleocapsid protein. All these compounds not only showed excellent pharmacokinetic properties, absorption, metabolism, minimal toxicity and bioavailability but were also remain stabilized at the active site of proteins during the MD simulation. Thus, the identified lead compounds may act as potential molecules for the development of effective drugs against SARS-CoV-2 by inhibiting the envelope formation, virion assembly and viral pathogenesis.

Keywords

SARS-CoV-2
Structural proteins
Molecular docking
Simulation
Virion
Envelope

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