ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern.

COVID-19, an infectious disease caused by the SARS-CoV-2 virus, emerged globally in early 2020 and has remained a serious public health issue. To date, although several preventative vaccines have been approved by FDA and EMA, vaccinated individuals increasingly suffer from breakthrough infections. Therapeutic antibodies may provide an alternative strategy to neutralize viral infection and treat serious cases; however, the clinical data and our experiments show that some FDA-approved monoclonal antibodies lose function against COVID-19 variants such as Omicron. Therefore, in this study, we present a novel therapeutic agent, SI-F019, an ACE2-Fc fusion protein whose neutralization efficiency is not compromised, but actually strengthened, by the mutations of dominant variants including Omicron. Comprehensive biophysical analyses revealed the mechanism of increased inhibition to be enhanced interaction of SI-F019 with all the tested spike variants, in contrast to monoclonal antibodies which tended to show weaker binding to some variants. The results imply that SI-F019 may be a broadly useful agent for treatment of COVID-19.

Human eukaryotic elongation factor 1A forms oligomers through specific cysteine residues.

Eukaryotic elongation factor 1A (eEF1A) is a multifunctional protein involved in bundling actin, severing microtubule, activating the phosphoinositol-4 kinase, and recruiting aminoacyl-tRNAs to ribosomes during protein biosynthesis. Although evidence has shown the presence of the isoform eEF1A1 oligomers, the substantial mechanism of the self-association remains unclear. Herein, we found that human eEF1A1 could spontaneously form oligomers. Specifically, mutagenesis screen on cysteine residues demonstrated that Cys(234) was essential for eEF1A1 oligomerization. In addition, we also found that hydrogen peroxide treatment could induce the formation of eEF1A oligomers in cells. By cysteine replacement, eEF1A2 isoform displayed the ability to oligomerize in cells under the oxidative environment. In summary, in this study we characterized eEF1A1 oligomerization and demonstrated that specific cysteine residues are required for this oligomerization activity.