Scientists at the Institut Pasteur have developed an innovative strategy to combat SARS-CoV-2. Rather than targeting a virus in constant mutation, they propose blocking the gateway used by the virus to penetrate our cells. This is achieved by nasal administration of an antibody that protects against all known variants, paving the way for new therapies aimed at vulnerable individuals. This work, which has emerged from an unprecedented collaboration involving five research units and five technology core facilities at the Institut Pasteur and DARRI*, is published in Nature Communications.
Since its emergence, the SARS-CoV-2 virus has not stopped evolving. Each new variant accumulates mutations in its spike protein, the 'key' enabling it to enter cells. As a result, therapeutic antibodies and vaccines designed to recognize this protein are gradually losing their efficacy against the most recent strains. Scientists are locked in a permanent race against time, pressed by the need to constantly adapt treatments to new versions of the virus that causes COVID-19.
The Institut Pasteur's scientists have opted to approach this challenge from a different perspective: rather than aiming for a changing viral target, why not block the binding point the virus needs to infect us?
The enzyme ACE2: the gateway for SARS-CoV-2
To infect our cells, SARS-CoV-2 needs to bind to a receptor on the cell surface: the enzyme ACE2. This acts as a lock for which the viral spike protein is the key. However, unlike the virus, our ACE2 receptor tends not to mutate.
"We have developed an antibody that binds to the ACE2 receptor, preventing the virus from binding to it," explains Simon Blachier, a PhD student at the Institut Pasteur and lead author of the study. "No matter how much the virus mutates, it can't infect us if it can't access its gateway."
The technical challenge lay in blocking access to the virus without disrupting the biological function of ACE2, an essential enzyme notably involved in regulating blood pressure.
A 'smart' antibody that protects but does not disrupt
The antibody developed, which was taken from an alpaca and named B07-Fc, has proven effective. Experiments conducted in vitro and on cell cultures have demonstrated that it meets the objectives set:
- Broad-spectrum efficacy: B07-Fc blocks all tested SARS-CoV-2 variants, including the most recent strains. By positioning itself at the site where the viral spike protein binds to ACE2, as revealed by structural studies, the antibody physically prevents the virus from binding to its receptor.
- Preservation of its enzymatic activity: Despite binding to the ACE2 receptor, the antibody does not interfere with this protein's function in cell models. It is therefore reasonable to assume that the blood pressure regulation system will remain operational.
Nasal administration
The team next tested the efficacy of B07-Fc in mice, opting for nasal administration. This route was chosen because the virus enters the body through the upper respiratory tract.
The results were conclusive: when administered nasally, the antibody conferred protection against SARS-CoV-2 infection in mice that had received an appropriate dose. If validated in preclinical testing, this approach could offer a number of benefits, as it is easy to administer, non-invasive, and provides targeted action at the viral point of entry.
A cross-disciplinary effort by Institut Pasteur scientists
This scientific breakthrough was the result of a combined effort by experts at the Institut Pasteur. As Anne Brelot, Inserm scientist and group leader in the Dynamics of Host-Pathogen Interactions Unit at the Institut Pasteur, points out: "The cross-cutting, multi-disciplinary and collaborative aspect of our study was key, with five technology core facilities and five research units at the Institut Pasteur involved. The publication is the culmination of this pooling of expertise."
Each step required specialist skills, from antibody production to X-ray crystallography and in vitro and in vivo experimentation on viral entry inhibition.
Hope for vulnerable patients
In addition to its value as scientific evidence, this study opens up opportunities, particularly for the most vulnerable individuals facing COVID-19. Immunocompromised patients or those that do not respond well to vaccination could benefit from this antibody as a preventive local treatment.
This approach also presents the strategic advantage of targeting a human element that does not vary, paving the way for a treatment that offers independence from future virus evolutions.
Although a number of additional steps are needed before it can be brought to market, this research marks an important milestone in developing a potential arsenal against COVID-19.
*DARRI : Department of Applications of Research and Relations with Industrials
Source :
Targeting ACE2 with a camelid antibodyinhibits SARS-CoV-2 binding and hasprotective effects in vivo, Nature Communications, November 21, 2025
Simon Blachier1, Marie-Christine Vaney2, Laurine Conquet3,4,12, Isabelle Staropoli5,12, Ignacio Fernández2, Emilie Giraud6, Atousa Arbabian2, Vincent Michel7, Fruzsina Szilagyi1, Salomé Guez6, Alix Boucharlat6, Jeanne Chiaravalli6, Jaouen Tran-Rajau6, Evelyne Dufour8, Ahmed Haouz9, Stéphane Petres8, Delphine Planas5,10, Xavier Montagutelli3, Fabrice Agou6, Pierre Lafaye11, Gabriel Ayme11,13, Olivier Schwartz5,10,13, Felix A. Rey2,13, Jost Enninga1,13 & Anne Brelot1
1Institut Pasteur, Université Paris Cité, Dynamics of Host-Pathogen Interactions Unit, CNRS UMR3691, F-75015 Paris, France.
2Institut Pasteur, Université ParisCité, Structural Virology Unit, CNRS UMR3569, F-75015 Paris, France.
3Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, F-75015 Paris, France.
4Institut Pasteur, Université Paris Cité, Mouse Genetics, Immunity and Infections Laboratory, F-75015 Paris, France.
5Institut Pasteur, Université Paris Cité, Virus and Immunity Unit, CNRS UMR3569, F-75015 Paris, France.
6Institut Pasteur, Université Paris Cité, Chemogenomic and Biological Screening Core Facility, C2RT, CNRS UMR3523, F-75015 Paris, France.
7Institut Pasteur, Université Paris Cité, Pathogenesis of Vascular Infections Unit, INSERM U1225, F-75015Paris, France.
8Institut Pasteur, Université Paris Cité, Production and Purification of recombinant Proteins Platform, CNRS UMR3528, F-75015 Paris, France.
9Institut Pasteur, Université Paris Cité, Crystallography Platform-C2RT, CNRS UMR3528, F-75015 Paris, France.
10Vaccine Research Institute, Créteil, France.
11Institut Pasteur, Université Paris Cité, Antibody Engineering Platform, CNRS UMR3528, F-75015 Paris, France.
12These authors contributed equally: LaurineConquet, Isabelle Staropoli.
13These authors jointly supervised this work: Gabriel Ayme, Olivier Schwartz, Felix A. Rey, Jost Enninga.
