ABSTRACT
Escape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers of single minibinders and fusions of three distinct minibinders were designed to geometrically match the SARS-CoV-2 spike (S) trimer architecture and were optimized by cell-free expression and found to exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent minibinders engage all three receptor binding domains on a single S trimer. The top candidates neutralize SARS-CoV-2 variants of concern with IC50 values in the low pM range, resist viral escape, and provide protection in highly vulnerable human ACE2-expressing transgenic mice, both prophylactically and therapeutically. Our integrated workflow promises to accelerate the design of mutationally resilient therapeutics for pandemic preparedness. One-Sentence SummaryWe designed, developed, and characterized potent, trivalent miniprotein binders that provide prophylactic and therapeutic protection against emerging SARS-CoV-2 variants of concern.
ABSTRACT
Objective To assess the comparability between different biochemical testing systems.Methods The research ana-lyzed the results of serum enzyme in two biochemical analyzer and figured out the bias estimation by the document of EP9-A2 and explored the comparison of AST、ALT、ALP、LDH and CK in different detected systems.Results It is indicated that in the differ-ent biochemical analysis systems,the comparability of all the indexes could be accepted except for ALP.Conclusion In order to provide a scientific basis for clinic results,comparability test between the methods should be performed and figured out the bias esti-mation while use different detecting systems to monitor the same index.
