Targeting the SARS-CoV-2-spike protein: from antibodies to miniproteins and peptides

Coronavirus disease-19, caused by the novel beta-coronavirus SARS-CoV-2, has created a global pandemic unseen in a century. Rapid worldwide efforts have enabled the characterization of the virus and its pathogenic mechanism. An early key finding is that SARS-CoV-2 uses spike proteins, the virus' most exposed structures, to bind to human ACE2 receptors and initiate cell invasion. Competitive targeting of the spike protein is a promising strategy to neutralize virus infectivity. This review article summarizes the discovery, binding modes and eventual applications of several classes of (bio)molecules targeting the spike protein: antibodies, nanobodies, soluble ACE2 variants, miniproteins, peptides and small molecules.

Automated summary

COVID-19 caused by the novel beta-coronavirus SARS-CoV-2 has led to a global pandemic unseen in a century. The virus uses spike proteins to bind to human ACE2 receptors for cell invasion, making competitive targeting of the spike protein a promising strategy to neutralize virus infectivity. Different classes of molecules targeting the spike protein have been discovered for potential applications, including antibodies, nanobodies, soluble ACE2 variants, miniproteins, peptides, and small molecules.