Le mardi 21 avril 2026, Madame Kristi LEKA, titulaire d'un d’un Master en Sciences pharmaceutiques à finalité spécialisée en conception et développement du médicament-bioanalyse et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques sous la direction de Madame Allison LEDOUX et de Monsieur Mutien-Marie GARIGLIANY.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Antiviral Drug Discovery Targeting Coronavirus Entry: Usambarensine as a Hid Compound". 

Le jury sera composé de :

Pierre FRANCOTTE (Président), Michel FREDERICH (Secrétaire), Pierre CHAMPY (Univ. Paris-Sarclay), Daniel DESMECHT, Mutien-Marie GARIGLIANY, Alexis HOSTE (UCB Pharma), Allison LEDOUX, Caroline STEVIGNY (ULB). 

Résumé de la thèse

RNA viruses represent a persistent threat to global public health due to their genetic plasticity, zoonotic origins, and capacity for rapid global dissemination. The repeated emergence of epidemics and pandemics, together with the limited availability of effective antiviral therapies, highlights the need for continued antiviral drug discovery. In this context, natural products remain a historically validated yet underexplored source of antiviral agents.

This thesis investigates the antiviral potential of alkaloids derived from Strychnos usambarensis against medically relevant RNA viruses. Using a bio-guided fractionation approach, the bis-indole alkaloid usambarensine was identified as the compound responsible for the observed antiviral activity. Antiviral screening against representative RNA viruses revealed selective, family-level activity against pathogenic coronaviruses, including SARS-CoV-2, SARS-CoV-1 and MERS-CoV, while limited or no activity was observed against unrelated viral families.
Mechanistic investigations indicate that usambarensine disrupts early stages of viral entry. The data are most consistent with inhibition at the membrane fusion step via the cathepsin-dependent endosomal pathway, with Cathepsin L emerging as a plausible molecular target. Although further biochemical and in vivo validation is required, this work provides the first evidence of antiviral activity associated with usambarensine and positions it as a promising lead scaffold for the development of family-specific antivirals.