De Novo Discovery of High Affinity Peptide Binders for the SARS-CoV-2 Spike Protein

The {beta}-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein, the most exposed surface structure of the virus, are of interest for the development of therapeutics and diagnostics. We used affinity selection-mass spectrometry for the rapid discovery of synthetic high affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants Kd = 80 to 970 nM) for RBD and selectivity over human serum proteins. Picomolar RBD concentrations in biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides might associate with the SARS-CoV-2-spike-RBD at a site unrelated to ACE2 binding, making them potential orthogonal reagents for sandwich immunoassays. We envision our discovery as a robust starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus directed delivery of therapeutics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/317131v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@803e9borg.highwire.dtl.DTLVardef@18e5d74org.highwire.dtl.DTLVardef@1998310org.highwire.dtl.DTLVardef@16ba5cc_HPS_FORMAT_FIGEXP M_FIG C_FIG

Effects of hawthorn leaf flavonoids on reducing blood lipids and preventing fatty liver in the quails / 复旦学报（医学版）

Objective To investigate the effect of hawthorn leaf flavonoids (HLFs) with the different concentrations in prevention of high blood lipids and fatty liver in quails. Methods Sixty quails were divided into six groups:normal (N),high lipids food model (M),positive control (ZBT),HLF1,HLF2 and HLF3 groups.The animals in the N group were fed with normal food,while the M group was feed with high lipids food to establish the animal model of fatty liver.Besides high-fat diet,HLF1,HLF2 and HLF3 groups were also fed with 1 mL HLFs in the doses of 20 mg/kg,40 mg/kg and 80 mg/kg respectively.The ZBT group was fed with 1 g/kg of ZhiBiTuo and used as the positive control.After the experiments of six months,the serum and liver of the quails were taken and used to evaluate the contents of total cholesterol (TC),triglyceride (TG),high density lipid cholesterol(HDL-C),low density lipid cholesterol (LDL-C),superoxide dismutase (SOD),malondialdehyde (MDA),glutathione (GSH),alanine amino transferase (ALT) and glutamic oxaloacetic transaminase (AST).Meanwhile,the microscopic and electronic microscopic sections were used to observe the pathological changes of the livers of the quails. Results Compared with the M group,HLFs significantly lowered the content of TC,TG,LDL-C,MDA,AST and ALT in the serum and livers of the quails in other groups (P<0.001).However,the levels of HDL-C,SOD and GSH of the other groups were increased markedly (P<0.001).Moreover,the ratios of increase/decrease in the three HLF groups were depended on the concentrations of HLFs.Also,better liver structure and less lipid accumulation were also observed in the HLF groups when compared to the M group. Conclusions These results showed HLFs can lower blood lipid and cholesterol accumulation,improve the antioxidant capacity and protect the physiological function of liver.So,HLFs were effective in preventing and treating high blood lipids and fatty liver induced by high-fat diet.