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Molecular dynamic simulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors |
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| Authors: | Nukoolkarn Veena Lee Vannajan Sanghiran Malaisree Maturos Aruksakulwong Ornjira Hannongbua Supot |
| Institution: | a Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand b Computational Simulation and Modeling Laboratory (CSML), Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand c Computer Chemistry Unit Cell (CCUC) Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand d Department of Chemistry, Faculty of Science, Rangsit University, Pathumtani 12000, Thailand |
| Abstract: | 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 3CLpro 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 3CLpro. The binding affinities of LPV and RTV to SARS-CoV 3CLpro 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. |
| Keywords: | SARS Proteinase MD simulations Ritonavir Lopinavir |
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