Preparation and characterization of nanobodies targeting SARS-CoV-2 papain-like protease

Coronavirus Papain-like protease (PLpro) mediates the cleavage of viral polyproteins and assists the virus escaping from innate immune response. Thus, PLpro is an attractive target for the development of broad-spectrum drugs as it has a conserved structure across different coronaviruses. In this study, we purified SARS-CoV-2 PLpro as an immune antigen, constructed a nanobody phage display library, and identified a set of nanobodies with high affinity for SARS-CoV-2. In addition, enzyme activity experiments demonstrated that two nanobodies had a significant inhibitory effect on the PLpro. These nanobodies should therefore be investigated as candidates for the treatment of coronaviruses.

Automated summary

Coronavirus Papain-like protease (PLpro) cleaves viral polyproteins and helps the virus evade immune response. PLpro is a potential target for broad-spectrum drugs due to its conserved structure. This study purified SARS-CoV-2 PLpro and identified high-affinity nanobodies that significantly inhibit its activity. These nanobodies should be further investigated for potential coronavirus treatment.