A comprehensive toolbox for timely phenotypic characterization of novel SARS-CoV-2 variants (PHENO-BOX)

The proposal aims at characterising clinically relevant phenotypic features of novel SARS-CoV-2 variants, namely: 1) Antiviral related phenotypes including - In vitro susceptibility to currently available DAAs and mAbs- In vitro and in vivo genetic barrier to resistance to currently available DAAs and mAbs- Susceptibility to synergistic drug combinations for isolates showing reduced susceptibility to one or more DAAs 2) Biological phenotypes including - Affinity of the virus Spike protein for the key ACE2 receptor as a proxy of in vivo infectivity - Ability of the variant to fuse cells in vitro (fusogenicity) as a proxy of in vivo pathogenicity- Cell entry route through TMPRSS2 mediated Spike cleavage vs. endosomal route 3) Immunity related phenotypes including - Susceptibility to neutralising antibodies and to cell mediated immunity Experimental data will be then shared with the scientific community through the web, providing a dynamic catalogue assisting studies investigating genotype-phenotype-clinical outcome association.