Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike protein

Abstract Background The outbreak and pandemic of coronavirus SARS-CoV-2 caused significant threaten to global public health economic consequences. It is extremely urgent that people must take actions develop safe effective preventions therapeutics. Nanobodies, which are derived from single?chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking spike interaction ACE2 protein were developed. Results Totally, four specific against its RBD domain screened a naïve VHH library. Among them, Nb91-hFc Nb3-hFc demonstrated activity by neutralizing pseudotyped viruses vitro. Subsequently, constructed improve the capacity. As result, heterodimer nanobody Nb91-Nb3-hFc exhibited strongest RBD-binding ability pseudoviruses an IC 50 value at approximately 1.54 nM. Conclusions present study indicated library could be used as potential resource for rapid acquisition exploitation nanobodies. Heterodimer may serve therapeutic agent treatment COVID-19.