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

doi:10.3390/cells12010083

Multiformin-Type Azaphilones Prevent SARS-CoV-2 Binding to ACE2 Receptor

Cells. 2022 Dec 25;12(1):83. doi: 10.3390/cells12010083.

Authors

Linda Jansen-Olliges¹, Shambhabi Chatterjee², Lili Jia^{3

4}, Frank Stahl⁴, Christian Bär², Marc Stadler^{5

6}, Frank Surup^{5

6}, Carsten Zeilinger¹

Affiliations

¹ Centre of Biomolecular Drug Research (BMWZ), Gottfried-Wilhelm-Leibniz Universität Hannover, Schneiderberg 38, 30167 Hannover, Germany.
² Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, OE 8886, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
³ Hubei International Scientific and Technological Cooperation Base of Traditional Fermented Foods, College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
⁴ Institute of Technical Chemistry, Gottfried-Wilhelm-Leibniz Universität Hannover, Callinstr. 5, 30167 Hannover, Germany.
⁵ Department Microbial Drugs, Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.
⁶ Institute of Microbiology, Technische Universität Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany.

Abstract

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.

Keywords: ACE2; SARS-CoV-2; protein microarray; protein-protein interaction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2 / metabolism
COVID-19*
Humans
Protein Binding
SARS-CoV-2* / metabolism

Substances

spike protein, SARS-CoV-2
Angiotensin-Converting Enzyme 2
azaphilone

Grants and funding

This work was supported by FOR 5170: CytoLabs—Systematische Untersuchung und Ausbeutung von Cytochalasanen and Excellence Cluster Rebirth Innovation-/Synergy Grants Screening of Telomerase Stimulators for Cardiac Regeneration & Repair (CR&R) by Cell Microarrays to C.Z and C.B. Lili Jia was financed by China Scholarship Council Br. 202006760071. This work was funded by the DFG (Deutsche Forschungsgemeinschaft) priority program “Taxon-Omics: New Approaches for Discovering and Naming Biodiversity” (SPP 1991). This work was supported by a research fellowship from the Deutsche Gesellschaft für Kardiologie—Herz und Kreislaufforschung e.V. (DGK01/2021) to S.C.