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

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. 2021 Feb 25;12(7):1793-1802. doi: 10.1021/acs.jpclett.0c03119.
Suresh Gangadevi 1,  Vishnu Nayak Badavath 2,  Abhishek Thakur 3,  Na Yin 1,  Steven De Jonghe 4,  Orlando Acevedo 3,  Dirk Jochmans 4,  Pieter Leyssen 4,  Ke Wang 5,  Johan Neyts 4,  Tao Yujie 6,  Galia Blum 2
Affiliations

Affiliations

  • 1 Anhui Provincial Engineering Laboratory of Silicon-Based Materials, Bengbu University, Caoshan Road 1866, Bengbu, Anhui 233030, PR China.
  • 2 Institute for Drug Research, The Hebrew University, Jerusalem 9112001, Israel.
  • 3 Department of Chemistry, University of Miami, Coral Gables, Florida 33146, United States.
  • 4 Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
  • 5 College of Material and Chemical Engineering, Bengbu University, Bengbu 233030, China.
  • 6 East China University of Political Science and Law, Shanghai 20042 China.
PMID: 33577324 DOI: 10.1021/acs.jpclett.0c03119
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.

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