C303 for COVID-19

C303 may be beneficial for COVID-19 according to the study below. COVID-19 involves the interplay of 400+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 11,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed C303 in detail.
Ball et al., Susceptibility of broad reactivity nanobodies to resistance mutations in the S2 domain of SARS-CoV-2 predicted by yeast display deep mutational scanning, Frontiers in Immunology, doi:10.3389/fimmu.2025.1726449
Introduction The rapid evolution of SARS-CoV-2 has led to the erosion of vaccine induced serum neutralization and monoclonal antibody efficacy. As such, interest is inevitably moving towards more conserved regions of the SARS-CoV-2 spike protein like the S2 domain. Resistance mutations continue to be a major obstacle for the development of antivirals and vaccines which target the RBD but what extent these will be a problem for S2 binding antibodies is not known. Methods We have developed a yeast display deep scanning mutagenesis platform which allows an unbiased prospective assessment of millions of single and double mutations for their effects on antibody binding to the S2 domain. Results We have compared the mutational resistance of a panel of five nanobodies mapped to four distinct non-competing epitopes within the conserved fusion peptide, stem helix and heptad repeat 2 elements of the S2 domain. Yeast display deep mutational scanning predicted reduced binding of C303, G223, G225, and G142 to naturally occurring resistance mutations which were experimentally confirmed on SARS-CoV-2 variants. Discussion Our study shows that resistance mutations in conserved elements of the S2 domain may still pose a challenge to the development of monoclonal antibodies and subunit vaccines.