TY - JOUR
T1 - Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19
AU - Gangadevi, Suresh
AU - Badavath, Vishnu Nayak
AU - Thakur, Abhishek
AU - Yin, Na
AU - De Jonghe, Steven
AU - Acevedo, Orlando
AU - Jochmans, Dirk
AU - Leyssen, Pieter
AU - Wang, Ke
AU - Neyts, Johan
AU - Yujie, Tao
AU - Blum, Galia
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/2/25
Y1 - 2021/2/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101682772&partnerID=8YFLogxK
U2 - 10.1021/acs.jpclett.0c03119
DO - 10.1021/acs.jpclett.0c03119
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C2 - 33577324
AN - SCOPUS:85101682772
SN - 1948-7185
VL - 12
SP - 1793
EP - 1802
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 7
ER -