Thread by @ejustin46

𝗜𝗻𝘀𝗶𝗴𝗵𝘁𝘀 𝗶𝗻𝘁𝗼 𝗦𝗔𝗥𝗦-𝗖𝗼𝗩-2 𝗽𝗮𝘁𝗵𝗼𝗴𝗲𝗻𝗶𝗰𝗶𝘁𝘆 𝗮𝗻𝗱 𝗰𝗲𝗹𝗹 𝗲𝗻𝘁𝗿𝘆 𝗽𝗮𝘁𝗵𝘄𝗮𝘆 𝘂𝘀𝗮𝗴𝗲

nature.com/articles/s4146…

2) The researchers performed deep mutational scanning of residues 808-855 of the SARS-CoV-2 spike protein, which spans the S2' cleavage site, fusion peptide and adjacent regions

3) They identified mutations at residue 813 upstream of the S2' cleavage site that reduced sensitivity to TMPRSS2-mediated cleavage and cell surface entry. Mutations S813V and S813K decreased virus virulence in mice.

4) The fusion peptide (residues 816-834) was found to have very low mutational tolerance, indicating its functional importance for membrane fusion.

5) An F823Y mutation in the fusion peptide conferred resistance to two broadly neutralizing antibodies (COV44-62 and COV44-79) that target this region. Structural modeling suggested the mutation disrupts antibody binding.

6) The findings provide insights into SARS-CoV-2 pathogenicity and cell entry pathway usage. They also highlight a potential challenge for developing pan-coronavirus vaccines targeting the fusion peptide region.

Thanks for reading 🙏