Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19.
J Phys Chem Lett
; 12(7): 1793-1802, 2021 Feb 25.
Article
in English
| MEDLINE | ID: covidwho-1081668
ABSTRACT
In the search for inhibitors of COVID-19, we have targeted the interaction between the human angiotensin-converting enzyme 2 (ACE2) receptor and the spike receptor binding domain (S1-RBD) of SARS-CoV-2. Virtual screening of a library of natural compounds identified Kobophenol A as a potential inhibitor. Kobophenol A was then found to block the interaction between the ACE2 receptor and S1-RBD in vitro with an IC50 of 1.81 ± 0.04 µM and inhibit SARS-CoV-2 viral infection in cells with an EC50 of 71.6 µM. Blind docking calculations identified two potential binding sites, and molecular dynamics simulations predicted binding free energies of -19.0 ± 4.3 and -24.9 ± 6.9 kcal/mol for Kobophenol A to the spike/ACE2 interface and the ACE2 hydrophobic pocket, respectively. In summary, Kobophenol A, identified through docking studies, is the first compound that inhibits SARS-CoV-2 binding to cells through blocking S1-RBD to the host ACE2 receptor and thus may serve as a good lead compound against COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Stilbenes
/
Drug Design
/
Spike Glycoprotein, Coronavirus
/
Receptors, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2021
Document Type:
Article
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