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INRAE

24, chemin de Borde Rouge -Auzeville - CS52627 31326 Castanet Tolosan cedex - France

Last update: May 2021

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Unité de Virologie et Immunologie Moléculaires

Position in the lab

28 June 2022

We are currently looking for a motivated student for a PhD to work on the field of antiviral treatments of the nasal cavity to limit aerial transmission.
Position in the lab

Antiviral treatment of the nasal cavity to limit the transmissibility of respiratory coronaviruses

Summary: Coronaviruses viruses have a very strong economic impact in the animal production and public health. The recent emergence in humans at the end of 2019 of SARS-CoV-2 and its variants, which have infected more than 500 million people worldwide, has highlighted their strong ability to disseminate. A similar event also occurred within the porcine species with the emergence and dissemination throughout the world during the 1980s of a variant of the transmissible gastroenteritis virus which acquired a respiratory tropism and lost its ability to multiply in the intestine. This virus called porcine respiratory coronavirus (CVRP) and SARS-CoV-2, which therefore have exceptional dissemination capacities, use two different receptors to penetrate the host cell, ACE2 for SARS-CoV-2 and APN for CVRP.

Blocking the spread of viruses that use the upper respiratory tract to multiply represents one of the great challenges in containing pandemics and epidemics. However, there are currently no effective inexpensive antivirals that can limit this dissemination. Generating inexpensive analogues of neutralizing antibodies delivered directly into the nasal cavity and the upper respiratory tract can represent a real interest in blocking the chains of transmission. We have already generated artificial proteins named αReps capable of neutralizing SARS-CoV-2 in vitro and in vivo. We are now improving the bioavailability of αReps in the nasal cavity and the PhD project will focus in characterizing their protective properties following their use in aerosol or by nebulization using the hamster and SARS-CoV-2 as a model. We will then validate this approach by producing αReps with a similar strategy directed against CVRP and then using them to limit the transmission of this virus in the pig model under breeding conditions.

We anticipate that we will be able to significantly block the dissemination of the virus in these two models of infection. Even if at present, the costs of anti-virals are not compatible in breeding; the antivirals that we are developing are very inexpensive, very resistant and effective at very low concentrations. These results could be extended to viral models such as porcine dysgenic and respiratory virus as well as bovine respiratory syncytial virus which represent a real and constant threat in their respective production chains. They will also make it possible to prepare a therapeutic arsenal with a view to future emerging zoonoses.

 

Profile: Candidates should have good knowledge in virology and be interested in protein biochemistry as well as animal model of physiopathology. She/he will mainly work with the VIM team in Jouy en Josas in collaboration with the GVB team in Ploufragan and the Virology team in Maison Alfort.

 

Contact:  nicolas.meunier@inrae.fr / yannick.blanchard@anses.fr / sophie.lepoder@vet-alfort.fr

 

References

Bryche B, St Albin A, Murri S, Lacote S, Pulido C, Ar Gouilh M, Lesellier S, Servat A, Wasniewski M, Picard-Meyer E, Monchatre-Leroy E, Volmer R, Rampin O, Le Goffic R, Marianneau P, Meunier N (2020) Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain, behavior, and immunity

Bryche B, Fretaud M, Saint-Albin Deliot A, Galloux M, Sedano L, Langevin C, Descamps D, Rameix-Welti MA, Eleouet JF, Le Goffic R, Meunier N (2019) Respiratory syncytial virus tropism for olfactory sensory neurons in mice. J Neurochem e14936

Desdouits M, Piquet JC, Wacrenier C, Le Mennec C, Parnaudeau S, Jousse S, Rocq S, Bigault L, Contrant M, Garry P, Chavanon F, Gabellec R, Lamort L, Lebrun L, Le Gall P, Meteigner C, Schmitt A, Seugnet JL, Serais O, Peltier C, Bressolette-Bodin C, Blanchard Y, Le Guyader FS. (2021). Can shellfish be used to monitor SARS-CoV-2 in the coastal environment? .Sci Total Environ. 778:146270.

Delmas, B., Gelfi, J., L’Haridon, R., Vogel, L.K., Sjostrom, H., Noren, O., and Laude, H. (1992). Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature 357, 417–420.

Sailleau, C., Dumarest, M., Vanhomwegen, J., Delaplace, M., Caro, V., Kwasiborski, A., Hourdel, V., Chevaillier, P., Barbarino, A., Comtet, L. and Le Poder, S. (2020). First detection and genome sequencing of SARS-CoV-2 in an infected cat in France. Transbound Emerg Dis.