Extended Data Fig. 3: Sequence conservation of the M protein and its binding pocket.

a, M protein sequence conservation across coronaviruses based on genomic sequence alignment. The B1 strain of SARS-CoV-2 genomic sequence of the M protein was aligned with corresponding sequences from viruses from the zoonotic reservoir from the sarbecovirus subfamily, Middle East respiratory syndrome virus (MERS-CoV), infectious bronchitis virus, HCoV-OC43, murine hepatitis virus, porcine epidemic diarrhoea virus, HCoV-229E, and HCoV-NL63. b, M protein sequence conservation of the binding pocket based on genomic sequence alignment. Sequence identity of the B1 strain of SARS-CoV-2 to sequences in the sarbecovirus family is > 90% for positions corresponding to the binding pocket of JNJ-9676. c, The M protein amino acid sequence in the binding pocket based on cryo-EM data was compared between the different viruses listed above based on the average Blosum score. To further assess the binding pocket conservation in sarbecoviruses, we downloaded the protein sequences classified into the sarbecovirus family (206 sequences, downloaded 25 June 2024) from the InterPro database. InterPro entry: IPR044361, M matrix/glycoprotein, SARS-CoV-like). Conservation analysis shows that 20 out of the 22 residues in the binding pocket of JNJ-9676 are completely conserved in proteins from the sarbecovirus family. The non-conserved positions correspond to SARS-CoV-2 residues C33 and I87.