tetano
Editor, Senior Moderator
Arch Med Sci. 2020 Mar 27;16(3):497-507. doi: 10.5114/aoms.2020.94046. eCollection 2020.
State-of-the-art tools to identify druggable protein ligand of SARS-CoV-2.
Azeez SA[SUP]1[/SUP], Alhashim ZG[SUP]1,[/SUP][SUP]2[/SUP], Al Otaibi WM[SUP]1[/SUP], Alsuwat HS[SUP]1[/SUP], Ibrahim AM[SUP]1,[/SUP][SUP]3[/SUP], Almandil NB[SUP]4[/SUP], Borgio JF[SUP]1,[/SUP][SUP]5[/SUP].
Author information
Abstract
Introduction:
The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2.
Material and methods:
State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands.
Results:
The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; DG = -10.2567 kcal/mol; pKi = 7.713 ?M) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; DG = -12.2112 kcal/mol; pKi = 7.885 ?M) of SARS-CoV-2.
Conclusions:
The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-of-the-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19.
Copyright: ? 2020 Termedia & Banach.
KEYWORDS:
COVID-19; SARS-CoV-2; druggable protein; envelope protein; ligand; molecular docking; nucleocapsid phosphoprotein; phylogenetic tree
PMID:32399095PMCID:PMC7212236DOI:10.5114/aoms.2020.94046
Free PMC Article
State-of-the-art tools to identify druggable protein ligand of SARS-CoV-2.
Azeez SA[SUP]1[/SUP], Alhashim ZG[SUP]1,[/SUP][SUP]2[/SUP], Al Otaibi WM[SUP]1[/SUP], Alsuwat HS[SUP]1[/SUP], Ibrahim AM[SUP]1,[/SUP][SUP]3[/SUP], Almandil NB[SUP]4[/SUP], Borgio JF[SUP]1,[/SUP][SUP]5[/SUP].
Author information
Abstract
Introduction:
The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2.
Material and methods:
State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands.
Results:
The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; DG = -10.2567 kcal/mol; pKi = 7.713 ?M) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; DG = -12.2112 kcal/mol; pKi = 7.885 ?M) of SARS-CoV-2.
Conclusions:
The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-of-the-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19.
Copyright: ? 2020 Termedia & Banach.
KEYWORDS:
COVID-19; SARS-CoV-2; druggable protein; envelope protein; ligand; molecular docking; nucleocapsid phosphoprotein; phylogenetic tree
PMID:32399095PMCID:PMC7212236DOI:10.5114/aoms.2020.94046
Free PMC Article