Design of novel copillar[4+1]arenes as ligands of SARS-CoV-2’s spike protein

Résumé

In December 2019, the emergence of SARS-CoV-2, a highly transmissible and pathogenic human coronavirus, led to global public health emergencies. The mechanism of the virus-host binding is still not fully known. Its understanding could lead to novel anti-viral strategies.[1] A first contact between viruses and host cells needs to be made before any link with receptors binding site. Sialic acids are often used by coronaviruses as primary recognition elements. This initiates viral entry into host cells, by a multi-step process in which the Receptor Binding Domain (RBD) of the spike glycoprotein binds the host ACE2 (Angiotensin Converting Enzyme 2) receptor. Then, conformational changes of the spike protein occur, leading to the fusion of viral and cellular membranes.[1–4] This reveals that the spike proteins play a crucial role in virus infection. In this project, we focus on the synthesis of heteromultivalent scaffolds such as copillar[4+1]arenes to exploit a multivalent effect to generate strong ligands of the SARS-CoV-2 spike protein (Figure 2).[5] Orthogonal couplings with biologically molecules namely sialic acid derivatives and specific peptides should achieve the design of such anti-viral molecules.[6]

la date de réponse	18 janv. 2023
langue originale	Anglais
L'institution diplômante	Universite de Namur
Superviseur	Stephane Vincent (Promoteur)