Molecular dynamic simulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors

J Theor Biol. 2008 Oct 21;254(4):861-7. doi: 10.1016/j.jtbi.2008.07.030. Epub 2008 Jul 29.


Since the emergence of the severe acute respiratory syndrome (SARS) to date, neither an effective antiviral drug nor a vaccine against SARS is available. However, it was found that a mixture of two HIV-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the SARS virus. To understand the fine details of the molecular interactions between these proteinase inhibitors and the SARS virus via complexation, molecular dynamics simulations were carried out for the SARS-CoV 3CL(pro) free enzyme (free SARS) and its complexes with lopinavir (SARS-LPV) and ritonavir (SARS-RTV). The results show that flap closing was clearly observed when the inhibitors bind to the active site of SARS-CoV 3CL(pro). The binding affinities of LPV and RTV to SARS-CoV 3CL(pro) do not show any significant difference. In addition, six hydrogen bonds were detected in the SARS-LPV system, while seven hydrogen bonds were found in SARS-RTV complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Computer Simulation*
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / drug effects
  • HIV Protease Inhibitors / therapeutic use*
  • Hydrogen Bonding
  • Ligands
  • Lopinavir
  • Models, Molecular*
  • Multienzyme Complexes
  • Protein Binding
  • Pyrimidinones / therapeutic use*
  • Ritonavir / therapeutic use*
  • Viral Proteins / chemistry*
  • Viral Proteins / drug effects


  • HIV Protease Inhibitors
  • Ligands
  • Multienzyme Complexes
  • Pyrimidinones
  • Viral Proteins
  • Lopinavir
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases
  • Ritonavir