Development, characterization and optimization of ligands targeting coronavirus Spikes

The viral spike of coronaviruses is a trimeric assembly of the S glycoprotein. In the viral cycle, the spike recognizes a specific receptor on the cell surface, angiotensin convertase II for SARS-CoV-2, SARS-CoV-1 and human coronavirus NL63, the latter antigenically distant from the phylogenetic lineage of SARS-CoVs.

We previously produced different peptidic ligands able to bind the Spike of SARS-CoV-2 and we are now improving their design through computational approaches.

Additionnaly, we aim at improving the resident time of these antiviral in the nasal cavity in order to block the transmission of the virus during risky contacts. We used successfully a strategy consisting of chimeric antiviral linked to mucin binding domain. While a potent antiviral against the Sars-CoV-2 Spike such as C2 is rapidly eliminated from the respiratory epithelium, its resident time is much increased after addition of such mucin binding domain. We now try to optimize this strategy and expand it to other respiratory viruses.