TY - JOUR
T1 - Statins and the Covid-19 main protease
T2 - In silico evidence on direct interaction
AU - Reiner, Željko
AU - Hatamipour, Mahdi
AU - Banach, Maciej
AU - Pirro, Matteo
AU - Al-Rasadi, Khalid
AU - Jamialahmadi, Tannaz
AU - Radenkovic, Dina
AU - Montecucco, Fabrizio
AU - Sahebkar, Amirhossein
N1 - Publisher Copyright:
Copyright © 2020 Termedia & Banach.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - 6LU7
KW - COVID-2019
KW - Docking
KW - Main protease
KW - Statins
UR - http://www.scopus.com/inward/record.url?scp=85085190038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085190038&partnerID=8YFLogxK
U2 - 10.5114/aoms.2020.94655
DO - 10.5114/aoms.2020.94655
M3 - Article
C2 - 32399094
AN - SCOPUS:85085190038
SN - 1734-1922
VL - 16
SP - 490
EP - 496
JO - Archives of Medical Science
JF - Archives of Medical Science
IS - 2
ER -