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  • PhD Student
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  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
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Scientific Fields
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Published in Antiviral Research - 05 Jan 2021

Sabrina Kalia, Corinne Jallet, Saliha Azebi, Thomas Cokelaer, Juliana Pipoli Da Fonseca, Yu Wu, Julien Barbier , Jean-Christophe Cintrat, Daniel Gillet, Noël Tordo

Link to Pubmed [PMID] – 33444703

Link to DOI – j.antiviral.2021.105016

Link to HAL - Pasteur – https://hal-pasteur.archives-ouvertes.fr/pasteur-03281530v1

Antiviral Res 188 (2021) 105016

ABMA and its analogue DABMA are two molecules of the adamantane family known to perturbate the endosomal pathway and to inhibit cell infection of several RNA and DNA viruses. Their activity against Rabies Virus (RABV) infection has already been demonstrated in vitro. (Wu et al., 2017, 2019). Here, we describe in more details their mechanism of action by comparison to Arbidol (umifenovir) and Ribavirin, two broad spectrum antivirals against emerging viruses such as Lassa, Ebola, influenza and Hantaan viruses. ABMA and DABMA, delivered 2 h pre-infection, inhibit RABV infection in vitro with an EC50 of 7.8 μM and 14 μM, respectively. They act at post-entry, by causing RABV accumulation within the endosomal compartment and DABMA specifically diminishes the expression of the GTPase Rab7a controlling the fusion of early endosomes to late endosomes or lysosomes. This may suggest that ABMA and DABMA act at different stages of the late endosomal pathway as supported by their different profile of synergy/antagonism with the fusion inhibitor Arbidol. This difference is further confirmed by the RABV mutants induced by successive passages under increasing selective pressure showing a particular involvement of the viral G protein in the DABMA inhibition while ABMA inhibition induces less mutations dispersed in the M, G and L viral proteins. These results suggest new therapeutic perspectives against rabies.

https://doi.org/10.1016/j.antiviral.2021.105016