Effective Drug Candidates against Global Pandemic of Novel Corona Virus (nCoV-2019): A Probability Check through

C G Bonde1, J Gawad1, R P Bhole2

  • 1Drug Design Laboratory, Department of Pharmaceutical Chemistry, SVKM's NMIMS School of Pharmacy and Technology Management, 425 405 Shirpur Campus, India.

Insights

Computational analysis identified Saquinavir as a potent drug candidate for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This antiretroviral medication shows promising binding to the virus

Area of Science:

  • Virology
  • Computational Chemistry
  • Drug Discovery

Background:

  • The global increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections necessitates urgent development of effective treatments.
  • Drug repurposing is a key strategy to rapidly identify potential therapies for novel viral diseases like COVID-19.

Purpose of the Study:

  • To identify potent, commercially available antiretroviral drugs for treating SARS-CoV-2 infection using computational methods.
  • To evaluate the efficacy of existing antiretroviral drugs against SARS-CoV-2 protease through molecular modeling.

Main Methods:

  • Utilized molecular modeling and molecular dynamics simulations to assess drug-protein interactions.
  • Performed free energy calculations to compare binding affinities of various antiretroviral agents to SARS-CoV-2 protease.
  • Analyzed structural flexibility and binding scores (G-score, E-model) of candidate drugs.

Main Results:

  • Saquinavir demonstrated superior binding affinity to the SARS-CoV-2 protease active site compared to Nelfinavir and Lopinavir.
  • Molecular dynamics studies indicated better binding of Saquinavir to the COVID-19 protease.
  • Saquinavir exhibited favorable G-score and E-model scores, suggesting significant therapeutic potential.

Conclusions:

  • Repurposing known protease inhibitors, particularly Saquinavir, is a viable strategy for treating SARS-CoV-2 infections.
  • Saquinavir shows promise as a first-line agent, potentially in combination with Ritonavir, for managing COVID-19.
  • Further clinical investigation into Saquinavir for SARS-CoV-2 treatment is warranted.