TY - JOUR

T1 - Multiformin-Type Azaphilones Prevent SARS-CoV-2 Binding to ACE2 Receptor

AU - Jansen-Olliges, Linda

AU - Chatterjee, Shambhabi

AU - Jia, Lili

AU - Stahl, Frank

AU - Bär, Christian

AU - Stadler, Marc

AU - Surup, Frank

AU - Zeilinger, Carsten

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/12/25

Y1 - 2022/12/25

N2 - 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.

AB - 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.

KW - ACE2

KW - protein microarray

KW - protein-protein interaction

KW - SARS-CoV-2

UR - http://www.scopus.com/inward/record.url?scp=85146029263&partnerID=8YFLogxK

U2 - 10.3390/cells12010083

DO - 10.3390/cells12010083

M3 - Article

VL - 12

JO - Cells

JF - Cells

SN - 2073-4409

IS - 1

M1 - 83

ER -