About: Computational Determination of Potential Inhibitors of SARS-CoV-2 Main Protease

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Computational Determination of Potential Inhibitors of SARS-CoV-2 Main Protease
Creator	Pham, Anh Pham, Le, Duc-Hung Ly, Thi Ngo, Son Quynh, Ngoc Vu, Van
Source	Medline; PMC
abstract	[Image: see text] The novel coronavirus (SARS-CoV-2) has infected several million people and caused thousands of deaths worldwide since December 2019. As the disease is spreading rapidly all over the world, it is urgent to find effective drugs to treat the virus. The main protease (Mpro) of SARS-CoV-2 is one of the potential drug targets. Therefore, in this context, we used rigorous computational methods, including molecular docking, fast pulling of ligand (FPL), and free energy perturbation (FEP), to investigate potential inhibitors of SARS-CoV-2 Mpro. We first tested our approach with three reported inhibitors of SARS-CoV-2 Mpro, and our computational results are in good agreement with the respective experimental data. Subsequently, we applied our approach on a database of ∼4600 natural compounds, as well as 8 available HIV-1 protease (PR) inhibitors and an aza-peptide epoxide. Molecular docking resulted in a short list of 35 natural compounds, which was subsequently refined using the FPL scheme. FPL simulations resulted in five potential inhibitors, including three natural compounds and two available HIV-1 PR inhibitors. Finally, FEP, the most accurate and precise method, was used to determine the absolute binding free energy of these five compounds. FEP results indicate that two natural compounds, cannabisin A and isoacteoside, and an HIV-1 PR inhibitor, darunavir, exhibit a large binding free energy to SARS-CoV-2 Mpro, which is larger than that of 13b, the most reliable SARS-CoV-2 Mpro inhibitor recently reported. The binding free energy largely arises from van der Waals interaction. We also found that Glu166 forms H-bonds to all of the inhibitors. Replacing Glu166 by an alanine residue leads to ∼2.0 kcal/mol decreases in the affinity of darunavir to SARS-CoV-2 Mpro. Our results could contribute to the development of potential drugs inhibiting SARS-CoV-2.
has issue date	2020-06-12(xsd:dateTime)
bibo:doi	10.1021/acs.jcim.0c00491
bibo:pmid	32530282
has license	no-cc
sha1sum (hex)	0119324f1e24ccfe582fc896d56c6de3a3579587
schema:url	https://doi.org/10.1021/acs.jcim.0c00491
resource representing a document's title	Computational Determination of Potential Inhibitors of SARS-CoV-2 Main Protease
has PubMed Central identifier	PMC7323056
has PubMed identifier	32530282
schema:publication	J Chem Inf Model
resource representing a document's body	covid:0119324f1e24ccfe582fc896d56c6de3a3579587#body_text
is schema:about of	named entity 'natural' named entity 'SARS-CoV-2' named entity 'Therefore' named entity 'compounds' named entity 'FPL' named entity 'worldwide' named entity 'disease' named entity 'respective' named entity 'SARS-CoV-2' named entity 'GOOD' named entity 'BONDS' named entity 'INHIBITOR' named entity 'INHIBITORS' named entity 'TO INVESTIGATE' named entity 'EFFECTIVE' named entity 'context' named entity 'effective' named entity 'SARS-CoV-2' named entity 'absolute' named entity 'SARS-CoV-2' named entity 'drugs' named entity 'binding' named entity 'binding' named entity 'SARS-CoV-2' named entity 'inhibitor' named entity 'inhibitors' named entity 'inhibiting' named entity 'SARS-CoV-2' named entity 'drug targets' named entity 'drugs' named entity 'epoxide' named entity 'refined' named entity 'simulations' named entity 'SARS-CoV-2' named entity 'FPL' named entity 'compounds' named entity 'kcal' named entity 'SARS-CoV-2' named entity 'peptide' named entity 'FEP' named entity 'van der Waals' named entity 'alanine' named entity 'SARS-CoV-2' named entity 'Molecular docking' named entity 'free energy perturbation' named entity 'protease' named entity 'Protease' named entity 'SARS-CoV-2' named entity 'SARS-CoV' named entity 'SARS-CoV-2' named entity 'infection' named entity 'Mpro' named entity 'Mpro' named entity 'NPT' named entity 'approved drug' named entity 'bat' named entity 'animals to humans' named entity 'HIV-1' named entity 'SARS-CoV-2' named entity 'Computer-aided drug design' named entity 'IC50' named entity 'Wuhan' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'lopinavir' named entity 'binding affinity of a ligand' named entity 'CPU time' named entity 'kcal' named entity 'center of mass' named entity 'SARS-CoV-2' named entity 'darunavir' named entity 'FEP' named entity 'mutation' named entity 'ritonavir' named entity 'severe acute respiratory syndrome coronavirus'

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