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Editor, Senior Moderator
Arch Med Sci. 2020 Apr 25;16(3):490-496. doi: 10.5114/aoms.2020.94655. eCollection 2020.
Statins and the COVID-19 main protease: in silico evidence on direct interaction.
Reiner Ž[SUP]1[/SUP], Hatamipour M[SUP]2,[/SUP][SUP]3[/SUP], Banach M[SUP]4,[/SUP][SUP]5[/SUP], Pirro M[SUP]6[/SUP], Al-Rasadi K[SUP]7[/SUP], Jamialahmadi T[SUP]8,[/SUP][SUP]9[/SUP], Radenkovic D[SUP]10[/SUP], Montecucco F[SUP]11,[/SUP][SUP]12[/SUP], Sahebkar A[SUP]13,[/SUP][SUP]8,[/SUP][SUP]14[/SUP].
Author information
Abstract
Introduction:
No proven drug and no immunisation are yet available for COVID-19 disease. The SARS-CoV-2 main protease (Mpro), a key coronavirus enzyme, which is a potential drug target, has been successfully crystallised. There is evidence suggesting that statins exert anti-viral activity and may block the infectivity of enveloped viruses. The aim of this study was to assess whether statins are potential COVID-19 Mpro inhibitors, using a molecular docking study.
Material and methods:
Molecular docking was performed using AutoDock/Vina, a computational docking program. SARS-CoV-2 Mpro was docked with all statins, while antiviral and antiretroviral drugs - favipiravir, nelfinavir, and lopinavir - were used as standards for comparison.
Results:
The binding energies obtained from the docking of 6LU7 with native ligand favipiravir, nelfinavir, lopinavir, simvastatin, rosuvastatin, pravastatin, pitavastatin, lovastatin, fluvastatin, and atorvastatin were -6.8, -5.8, -7.9, -7.9, -7.0, -7.7, -6.6, -8.2, -7.4, -7.7, and -6.8 kcal/mol, respectively. The number of hydrogen bonds between statins and amino acid residues of Mpro were 7, 4, and 3 for rosuvastatin, pravastatin, and atorvastatin, respectively, while other statins had two hydrogen bonds.
Conclusions:
These results indicate, based upon the binding energy of pitavastatin, rosuvastatin, lovastatin, and fluvastatin, that statins could be efficient SARS-CoV-2 Mpro inhibitors. This is supported by the fact that the effects of some statins, especially pitavastatin, have a binding energy that is even greater than that of protease or polymerase inhibitors. However, further research is necessary to investigate their potential use as drugs for COVID-19.
Copyright: ? 2020 Termedia & Banach.
KEYWORDS:
6LU7; COVID-2019; docking; main protease; statins
PMID:32399094PMCID:PMC7212226DOI:10.5114/aoms.2020.94655
Free PMC Article
Statins and the COVID-19 main protease: in silico evidence on direct interaction.
Reiner Ž[SUP]1[/SUP], Hatamipour M[SUP]2,[/SUP][SUP]3[/SUP], Banach M[SUP]4,[/SUP][SUP]5[/SUP], Pirro M[SUP]6[/SUP], Al-Rasadi K[SUP]7[/SUP], Jamialahmadi T[SUP]8,[/SUP][SUP]9[/SUP], Radenkovic D[SUP]10[/SUP], Montecucco F[SUP]11,[/SUP][SUP]12[/SUP], Sahebkar A[SUP]13,[/SUP][SUP]8,[/SUP][SUP]14[/SUP].
Author information
Abstract
Introduction:
No proven drug and no immunisation are yet available for COVID-19 disease. The SARS-CoV-2 main protease (Mpro), a key coronavirus enzyme, which is a potential drug target, has been successfully crystallised. There is evidence suggesting that statins exert anti-viral activity and may block the infectivity of enveloped viruses. The aim of this study was to assess whether statins are potential COVID-19 Mpro inhibitors, using a molecular docking study.
Material and methods:
Molecular docking was performed using AutoDock/Vina, a computational docking program. SARS-CoV-2 Mpro was docked with all statins, while antiviral and antiretroviral drugs - favipiravir, nelfinavir, and lopinavir - were used as standards for comparison.
Results:
The binding energies obtained from the docking of 6LU7 with native ligand favipiravir, nelfinavir, lopinavir, simvastatin, rosuvastatin, pravastatin, pitavastatin, lovastatin, fluvastatin, and atorvastatin were -6.8, -5.8, -7.9, -7.9, -7.0, -7.7, -6.6, -8.2, -7.4, -7.7, and -6.8 kcal/mol, respectively. The number of hydrogen bonds between statins and amino acid residues of Mpro were 7, 4, and 3 for rosuvastatin, pravastatin, and atorvastatin, respectively, while other statins had two hydrogen bonds.
Conclusions:
These results indicate, based upon the binding energy of pitavastatin, rosuvastatin, lovastatin, and fluvastatin, that statins could be efficient SARS-CoV-2 Mpro inhibitors. This is supported by the fact that the effects of some statins, especially pitavastatin, have a binding energy that is even greater than that of protease or polymerase inhibitors. However, further research is necessary to investigate their potential use as drugs for COVID-19.
Copyright: ? 2020 Termedia & Banach.
KEYWORDS:
6LU7; COVID-2019; docking; main protease; statins
PMID:32399094PMCID:PMC7212226DOI:10.5114/aoms.2020.94655
Free PMC Article