Open AccessKobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19
Author(s) -
Suresh Gangadevi,
Vishnu Nayak Badavath,
Abhishek Thakur,
Na Yin,
Steven De Jonghe,
Orlando Acevedo,
Dirk Jochmans,
Pieter Leyssen,
Ke Wang,
Johan Neyts,
Yujie Tao,
Galia Blum
Publication year - 2021
Publication title -
the journal of physical chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.563
H-Index - 203
ISSN - 1948-7185
DOI - 10.1021/acs.jpclett.0c03119
Subject(s) - docking (animal) , receptor , covid-19 , binding site , chemistry , ic50 , virtual screening , lead compound , plasma protein binding , biophysics , angiotensin converting enzyme 2 , in vitro , biology , biochemistry , drug discovery , medicine , infectious disease (medical specialty) , nursing , disease , pathology
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 IC 50 of 1.81 ± 0.04 μM and inhibit SARS-CoV-2 viral infection in cells with an EC 50 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.