Data File Descriptions and Methods [betacov_matching_IPR042578.fasta]: Representative set of 2,465 betacoronavirus S protein overlapping homologous superfamily sequences retreived in fasta format on 4 December 2022 from the InterPro repository at https://www.ebi.ac.uk/interpro/entry/InterPro/IPR042578/. [betacov_matching_IPR042578_motif.fasta]: Extracted 98,122 furin cleavage site (FCS) motifs of 20 amino acid length, including overlapping sequences, using the FindFur algorithm as described by (Gu, 2020) and deposited on 15 December 2020 at the GitHub software repository at https://github.com/chwisteeng/FindFur. These sequences were individually checked for The/Ser O-glycosite residue pairs with the standard prediction software NetOGlyc4.0 (Steentoft et al., 2013) as available at https://services.healthtech.dtu.dk/services/NetOGlyc-4.0/. The bioinformatics nuclear localization signal (NLS) predictions, specifically including the positive hits for pat7 in SARS-CoV-2 and in MERS_MA30 CoV, used the PSORT algorithm available as a webservice at https://wolfpsort.hgc.jp/ which is based on the work of Nakai and Horton (Nakai and Horton, 1999). [betacov_s1s2_nls_pat7_furin_blastp.txt]: Comprehensive sequence database searches using were performed using the NCBI protein BLAST (BLASTP) algorithm with webservice available at https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins. The following BLASTP search parameters and settings were used: Word size=2; Expect value=200000; Hitlist size=500; Gapcosts=9,1; Matrix=PAM30; Filter string=F; Genetic Code=1;Window Size=40; Threshold=11; Composition-based stats=0; Database Posted date=Jan 19, 2023 2:59 AM; Number of letters=17,117,563; Number of sequences=10,766; Entrez query: Includes: Betacoronavirus (taxid:694002); Excludes: SARS-CoV-2 (taxid:2697049). The six polyfunctional input query consensus motif sequences were TXXPR(K/H/R)XRSX and TXXPRX(K/H/R)RSX. [table_s1s2_hits_betacov_polyf.pdf]: Compiled summary table of hits (PDF) representing S1/S2 spike domains across genus Betacoronavirus. [table_s1s2_hits_betacov_polyf.xlsx]: Compiled summary table of hits (MS Excel) representing S1/S2 spike domains across genus Betacoronavirus. References Gu, C., 2020. FindFur: A Tool for Predicting Furin Cleavage Sites of Viral Envelope Substrates. Master’s Thesis, San Jose State University, CA, USA. doi: 10.31979/etd.4ahv-9jya Nakai, K., Horton, P., 1999. PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization. Trends Biochem Sci 24, 34–36. doi: 10.1016/s0968-0004(98)01336-x Steentoft, C., Vakhrushev, S.Y., Joshi, H.J., Kong, Y., Vester-Christensen, M.B., Schjoldager, K.T.-B.G., Lavrsen, K., Dabelsteen, S., Pedersen, N.B., Marcos-Silva, L., Gupta, R., Bennett, E.P., Mandel, U., Brunak, S., Wandall, H.H., Levery, S.B., Clausen, H., 2013. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology. EMBO J 32, 1478–1488. doi: 10.1038/emboj.2013.79