Mechanism of action of phthalazinone derivatives against rabies virus

Antiviral Res. 2024 Feb 17:105838. doi: 10.1016/j.antiviral.2024.105838. Online ahead of print.ABSTRACTRabies, a viral zoonosis, is responsible for almost 59,000 deaths each year, despite the existence of an effective post-exposure prophylaxis. Indeed, rabies causes acute encephalomyelitis, with a case-fatality rate of 100 % after the onset of neurological clinical signs. Therefore, the development of therapies to inhibit the rabies virus (RABV) is crucial. Here, we identified, from a 30,000 compound library screening, phthalazinone derivative compounds as potent inhibitors of RABV infection and more broadly of Lyssavirus and even Mononegavirales infections. Combining in vitro experiments, structural modelling, in silico docking and in vivo assays, we demonstrated that phthalazinone derivatives display a strong inhibition of lyssaviruses infection by acting directly on the replication complex of the virus, and with noticeable effects in delaying the onset of the clinical signs in our mouse model.PMID:38373533 | DOI:10.1016/j.antiviral.2024.105838

Source: Antiviral Research - February 19, 2024 Category: Virology Authors: Victoire Perraud Bart Vanderhoydonck Guillaume Bouvier Guilherme Dias de Melo Amuri Kilonda Mohamed Koukni Dirk Jochmans Sophie Rog ée Youcef Ben Khalifa Lauriane Kergoat Julien Lannoy Tina Van Buyten Nadia Izadi-Pruneyre Patrick Chaltin Johan Neyts Arna Source Type: research