FIGHTING-OFF CORONAVIRUS (SARS-CoV-2) WITH BROAD-SPECTRUM ANTIVIRALS: ESTABLISHING ANIMAL VIRAL CHALLENGE MODEL

Project coordinator: Professor Anna-Lena Spetz, MD, PhD, Stockholm University, Sweden Objectives of proposal: Our consortium 'ÄúFight-nCoV'Äù will accelerate preclinical development of new broad-spectrum antivirals for inhalation, building on breath-taking ongoing research. We will determine and characterize the antiviral activity and safety of three viral entry inhibitors (oligonucleotide, Macro-I, tweezer) against SARS-CoV-2 in vitro and in vivo. To enable this, we will build capacity for evaluation of antiviral efficacy against SARS-CoV-2 in vitro using viral pseudotypes and wild-type SARS-CoV-2 as well as in vivo in non-human primates. Safety studies will be performed according to OECD GLP guidelines. Expected results: We will establish a SARS-CoV-2 spike pseudotype system allowing a standardized high throughput evaluation of the antiviral activity of candidate drugs. We will have determined the antiviral efficacy of three novel broad-spectrum viral entry inhibitors: oligonucleotide, macromolecular polymers, and molecular tweezers. We will also build capacity for innovation and preclinical evaluation of our broad-spectrum antivirals and vaccines against SARS-CoV-2 by establishing a macaque challenge model. 'ÄúFight-nCoV'Äù will provide efficacy data of our drug candidates given intranasally in non-human primates challenged with SARS-CoV-2, enable an early and valuable outcome for stakeholders and the civil society. Timeline of proposal: Ongoing-24 months Key partners: Roger Le Grand, Director animal facility, CEA, France; Urban H√∂glund, CEO Adlego Biomedical, Sweden; Jan M√ºnch, Professor in Molecular Virology, UULM, Germany; Alexander Zelikin, Associate Professor, formulation expert, AU, Denmark; and Thomas Schrader, Professor of Chemistry, UDE, Germany.