Acetylation

Pathology

Cell

Receptor

Glycan

Virus

N-Acetylneuraminic acid

Disease

Sialic acid

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Gene

Glycoprotein

Infectivity

Virology

Chemistry

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Biochemistry

Medicine

Nature Communications

The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor in the infection, others suggest the important role of cell attachment factors such as glycans. Here, we use atomic force microscopy to study these early binding events with the focus on the role of sialic acids (SA). We show that SARS-CoV-2 binds specifically to 9- O -acetylated-SA with a moderate affinity, supporting its role as an attachment factor during virus landing to cell host surfaces. For therapeutic purposes and based on this finding, we have designed novel blocking molecules with various topologies and carrying a controlled number of SA residues, enhancing affinity through a multivalent effect. Inhibition assays show that the AcSA-derived glycoclusters are potent inhibitors of cell binding and infectivity, offering new perspectives in the treatment of SARS-CoV-2 infection.

Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection