News 2020

Délivrance française de notre brevet d’invention (WO2018/073549) sur de nouvelles compositions antivirales pour le traitement des infections liées aux coronavirus.

L’invention concerne le repositionnement de molécules pour de nouvelles indications antivirales prophylactiques et thérapeutiques contre le coronavirus MERS-CoV (Middle East Respiratory Syndrome-related Coronavirus) chez l’homme et chez les animaux. Signia Therapeutics possède les droits internationaux exclusifs pour ce brevet d’invention.

Our last collaborative study with on Combinations of Baloxavir acid and other inhibitors against seasonal influenza A viruses has been published in Viruses.

Antivirals are recommended for the treatment and control of epidemics and pandemics influenza viruses, especially in high risk populations. Therapeutic combinations constitute an alternative to prevent resistance andreduce antiviral doses. In this way, in collaboration with the Research Centre in Infectious Diseases of CHU Québec and Laval University, we assessed the inhibitory effects of Baloxavir with three NAIs (oseltamivir, zanamivir and peramivir) or two other polymerase inhibitors (favipiravir and ribavirin) in cell culture and in predictive human airway epithelia (HAE) models of infection with influenza A(H1N1)pdm09 and A(H3N2) viruses. Our results suggest that Baloxavir stands as a potential good candidate for combination therapy with several existing drugs to improve antiviral activity and eventually delay drug resistance of influenza type A viruses. Combination therapies with Baloxavir should be further considered for animal studies and clinical investigations.

Reportage du journal du CNRS sur la recherche d'un médicament efficace contre le virus SARS-CoV-2 en un temps record. Une course contre la montre qui se déroule in vitro, in vivo et même... in silico.

Our article on human RSV-induced immune signature of infection is now published in The Journal of Infectious Diseases.

In this study, we applied a tailored transcriptomics workflow to exploit nasal wash samples from children who tested positive for HRSV. Our analysis revealed a characteristic immune signature as a direct reflection of HRSV pathogenesis and highlighted putative biomarkers of interest such as IP-10, TMEM190, MCEMP1 or TIMM23.

Les résultats de notre étude sur les effets de l’hydroxychloroquine, associée ou non à l’azithromycine, dans un modèle d’infection expérimentale chez le macaque par le virus SARS-CoV-2 ont été publiés dans la revue Nature.

Notre laboratoire VirPath est fier d’avoir participé à ce travail collaboratif mené par le CEA, l'Inserm, l'Institut Pasteur, le CNRS - Centre national de la recherche scientifique, l’Université de Paris-Saclay, APHM (Assistance Publique - Hopitaux de Marseille) et Aix-Marseille Université, sous l’égide du consortium multidisciplinaire REACTing. Nos modèles d’infection en épithélium respiratoire humain reconstitué ont été prédictifs des résultats obtenus en modèle de primate, qui démontrent que l’hydroxychloroquine n’a pas d’efficacité antivirale in vivo, et ce malgré une exposition pulmonaire importante.

Our article on the characterization of human reconstituted airway epithelial models of SARS-CoV-2 infection and their use for the preclinical evaluation of antiviral candidates is now published in Cell Reports Medecine.

In this study, we provide evidence on the antiviral efficacy of Remdesivir and the therapeutic potential of the Remdesivir-Diltiazem combination as a rapidly available and promising option to respond to the current medical need imposed by COVID-19. This combination of a virus-directed plus a host-directed drug stimulating endogenous expression of type I and type III interferons could not only result in enhanced antiviral and/or immunomodulatory effects, but also reduce the therapeutic doses of chemotherapeutic agents targeting nucleic acid synthesis in order to minimize putative adverse side effects.

Our comment on France's COVID-19 response is now published in The Lancet.

Our article on the in vitro evaluation of compounds, known for their cellular broad-spectrum activities, together with drugs that are under evaluation in clinical trials for COVID-19 patients is now published in Antiviral Research.

In this study, we report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection. Virus-directed plus host-directed drug combinations were also investigated. We report strong antagonism for remdesivir/berberine and high level of synergy for remdesivir/diltiazem drug combinations. These combinations of host-directed drugs with direct acting antivirals open interesting avenues for the treatment of COVID-19.

The aim of this R&D project is to develop and characterize a model of metapneumovirus (hMPV) infection in the non-human primate (NHP) Cynomolgus in order to meet current unmet needs for the development and preclinical evaluation of prophylactic or therapeutic solutions against these respiratory infections, which are a major global health and economic issue.

The aims of the project are (i) to develop, validate and characterize a PNH model of hMPV infection and (ii) to use this model to validate the preclinical efficacy of a new nebulized delivery method for a drug repositioned by Signia Therapeutics (Dilitiazem) as a new-generation antiviral (patent WO/2019/224489 A1) and to accelerate its transfer to phase 2 clinical trials (the project's ultimate aim).

The consortium is made up of three players based in the Auvergne-Rhône-Alpes region, whose complementarity will be used to innovate: Cynbiose and Signia Therapeutics are the industrial partners and the VirPath laboratory is the academic partner.