Zhao Jincun’s Research Team from the lab collaborated with units including Nanjing GenScript Biotech Corporation, IQTC (P3 Lab), and Shenzhen Bay Lab, to clarify that the recombinant hACE2-Fc has an effective preventive and therapeutic therapeutic efficacy against SARS-CoV-2 infection in vivo, confirming that it may be a potential clinical treatment for COVID-19. Related paper “Potent Prophylactic and Therapeutic Efficacy of Recombinant Human ACE2-Fc against SARS-CoV-2 Infection in Vivo” was published in Cell Discovery on August 13, 2021.

This research studied the inhibitory effect of recombinant hACE2-Fc against SARS-CoV-2 in vitro and in vivo in detail. The research found that both hACE2-Fc WT and hACE2-Fc Mutant (carrying inactivating mutants of ACE2) can bind to the spike protein and receptor binding domain protein (RBD) of SARS-CoV-2 with high affinity in vitro. Further neutralization test against SARS-CoV-2 wild-type live virus and SARS-CoV-2 multiple mutant strains showed that both hACE2-Fc WT and Mutant have good neutralizing effects on SARS-CoV-2 wild-type virus and mutant strains, and strong neutralization capability for human coronaviruses SARS-CoV and HCoV-NL63 with ACE2 as a receptor. In the presence of hACE2-Fc, for continuous passage of SARS-CoV-2 on susceptible cells, mutations did not arise in the receptor-binding domain, proving that new virus strains will not escape during clinical application. In addition, both hACE2-Fc WT and Mutant can effectively protect SARS-CoV-2 from infection of human bronchial epithelial cells, suggesting the feasibility of hACE2-Fc in clinical treatment.

The research team further uses the mouse model infected with COVID-19 of human ACE2 transduced by adenovirus established in the early stage in the lab to verify the protective effect of hACE2-Fc in vivo. It was found that compared with the control group, when hACE2-Fc WT or Mutant was given before or after SARS-CoV-2 infection, the viral titer in the lungs of mouse infected with SARS-CoV-2 was significantly reduced, the weight increased rapidly, and pulmonary pathological damage was reduced. Meanwhile, it is found that the protective effect in vivo is obviously dose-dependent with the dosage of hACE2-Fc. The results of pharmacokinetics showed that the half-life of hACE2-Fc in mice can be as long as 29 hours, which is longer than the half-life of soluble recombinant hACE2, which is conducive to the long-term protection of hACE2-Fc in vivo.

Original paper：https://www.nature.com/articles/s41421-021-00302-0