Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig

Preamble:
- The SPIKE protein or S protein or spirulina protein surrounds the viral particle and forms the tips of its crown. It is this protein that allows the virus to infect human cells.
- SARS and SARS-COV-2 viruses use their S proteins to enter the cell by interacting with proteins called ACE2 (angiotensin 2 converting enzyme) present on the cell surface
- Several in vitro studies and in vivo trials on a humans shows that the recombinant ACE2, and a fortiori those associated with an FC, can be protective against ARDS which can occur in SARS-COV after SARS-COVID-2 infection
- The effects being more durable with the recombinant form associated with FC than simple recombinant form.
- A pseudotyped * virus is a virus, or a part of a virus, combined with an envelope of foreign origin and is devoid of genetic material
- The TIGIT ** protein (T cell immunoreceptor with the Ig and ITIM domains) is a co-inhibitor receptor which has been reported to suppress autoreactive T and B cells to ensure immunological tolerance, in particular, tested in lupus autoimmune models.
- All the antibodies possibly neutralizing SARS-COV do not have cross-reactivity with SARS-COV 2

Results:

Characteristics of the 2 proteins developed for this study:
o 1st: ACE2-Ig: extracellular domain of ACE2 associated with the FC fragment of a human IgG1
o 2nd: m-ACE2-Ig: ACE2 variant: 2 histidines (h374 and h378) are replaced by asparagines to decrease the catalytic activity of ACE2

Results with the 2 proteins created, comparison with TIGIT Ig **
o In vitro, these two protein constructs had a high affinity for SARS-Cov and SARS-COV 2
o In vivo on mice, these two antibodies were highly stable with an very high stability for the variant: m-ACE2-Ig
o In vitro, the pseudotyped virus * (Glycoprotein S of the viruses) is neutralized by the protein constructs.
o No cardiovascular side effect observed in mouse models