Multiformin-Type Azaphilones Prevent SARS-CoV-2 Binding to ACE2 Receptor
Linda Jansen-Olliges,
Shambhabi Chatterjee,
Lili Jia,
Frank Stahl,
Christian Bär,
Marc Stadler,
Frank Surup,
Carsten Zeilinger
Affiliations
Linda Jansen-Olliges
Centre of Biomolecular Drug Research (BMWZ), Gottfried-Wilhelm-Leibniz Universität Hannover, Schneiderberg 38, 30167 Hannover, Germany
Shambhabi Chatterjee
Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, OE 8886, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
Lili Jia
Hubei International Scientific and Technological Cooperation Base of Traditional Fermented Foods, College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
Frank Stahl
Institute of Technical Chemistry, Gottfried-Wilhelm-Leibniz Universität Hannover, Callinstr. 5, 30167 Hannover, Germany
Christian Bär
Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, OE 8886, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
Marc Stadler
Department Microbial Drugs, Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany
Frank Surup
Department Microbial Drugs, Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany
Carsten Zeilinger
Centre of Biomolecular Drug Research (BMWZ), Gottfried-Wilhelm-Leibniz Universität Hannover, Schneiderberg 38, 30167 Hannover, Germany
Protein microarray screenings identified fungal natural products from the azaphilone family as potent inhibitors of SARS-CoV-2 spike protein binding to host ACE2 receptors. Cohaerin F, as the most potent substance from the cohaerin group, led to more than 50% less binding of ACE2 and SARS-CoV-2 spike protein. A survey for structurally related azaphilones yielded the structure elucidation of six new multiformins E–J (10–15) and the revision of the stereochemistry of the multiformins. Cohaerin and multiformin azaphilones (1–5, 8, 12) were assessed for their activity in a cell-based infection assay. Calu-3 cells expressing human ACE2 receptor showed more than 75% and 50% less infection by SARS-CoV-2 pseudotyped lentivirus particles after treatment with cohaerin C (1) and cohaerin F (4), respectively. Multiformin C (8) and G (12) that nearly abolished the infection of cells. Our data show that multiformin-type azaphilones prevent the binding of SARS-CoV-2 to the cell entry receptor ACE2.
