Development of potent remdesivir derivative against SARS-CoV-2 protease inhibitors: Design, modification, molecular modeling and MD simulations

Pak J Pharm Sci. 2021 May;34(3(Supplementary)):1119-1126.

Abstract

The pandemic Coronavirus (Covid-19) is continuously growing and spreading at the highest rate in all over the world. So, it is necessary to produce the new medicinal agents against this virus. The aim of the present study is to design a potent compound against COVID-19. Based on 3C-like main protease and recently developed solved structure (PDB ID: 6Y2F), a series of remdesivir analogs are designed and analyzed by employing molecular modeling against the SARS-CoV-2 by insilico approach. The molecular dynamics (MD) simulation for 500ps was performed to check the stability and orientation to inside the binding pocket for analogs R3, R9, R14 and R15. The study results exhibit that compsound R9 has strong interaction or least binding energy (-10.04kcal/mol) as compare to the other analogues due to the presences of methyl bromide and it may be useful to further investigation in vitro testing against Covid-19.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Antiviral Agents / therapeutic use*
  • COVID-19 Drug Treatment*
  • Humans
  • Molecular Docking Simulation
  • Pandemics / prevention & control
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / therapeutic use*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • remdesivir
  • Adenosine Monophosphate
  • Peptide Hydrolases
  • Alanine