Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19

Suresh Gangadevi, Vishnu Nayak Badavath, Abhishek Thakur, Na Yin, Steven De Jonghe, Orlando Acevedo, Dirk Jochmans, Pieter Leyssen, Ke Wang, Johan Neyts, Tao Yujie, Galia Blum

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1793-1802
Number of pages10
JournalJournal of Physical Chemistry Letters
Volume12
Issue number7
DOIs
StatePublished - Feb 25 2021
Externally publishedYes

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry

Fingerprint Dive into the research topics of 'Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19'. Together they form a unique fingerprint.

Cite this