Perimentally verified, yielding 168,094 proteins �ll (Ka et al., 2004; Sonnhammer et al., 1998). Of those proteins, we applied a Topoisomerase Formulation sliding window method to assess nearby density of cysteine residues about the transmembrane helices. Especially, we scanned the thirty-residue regions that lie around the N- or C- terminal sides of each and every transmembrane helix, making use of a window size of 20. For every protein, the transmembrane-adjacent window together with the highest fraction of cysteine was taken as the protein’s cysteine fractional `score’. The total set of protein scores is offered in Supplementary file 2. To summarize high-confidence hits, we 1st removed redundancy by filtering for duplicate sequence entries that originated from strain-specific sequence deposition. This final set is provided as Supplementary file two, with high-density hits named out in Figure 5G. In parallel, we acquired the full set of human proteins (n = 20370) from Uniprot (information retrieved October 2020) (UniProt Consortium, 2015). We then similarly filtered for predicted trans�ll membrane proteins, yielding 5182 candidates (Ka et al., 2004; Sonnhammer et al., 1998). Of these proteins, we applied precisely the same sliding window strategy as for viral proteins as described above. The complete set of protein scores is offered in Supplementary file 3. We further subjected these putatively cysteine-rich transmembrane proteins to manual filtering to identify `spikelike’ human proteins, which feature cysteine motifs in cytosol and aromatics in the ectodomainplasma membrane interface. Final results are summarized in Figure 5H with gene ontology (PantherDB) presented in Figure 5–figure supplement 1D.AcknowledgementsWe thank all Brangwynne Lab members for helpful discussion and critiques and Evangelos Gatzogiannis for help with live cell microscopy. AD wishes to thank the Hargrove lab at Duke University, and specifically Sarah Wicks, for assistance and use of your ChemAxon analysis application, at the same time as Dr. Brittany Morgan for useful discussions. This perform was supported by Princeton COVID-19 study funds by way of the Workplace of your Dean for Investigation (CPB and AP labs); the Howard Hughes Health-related Institute (CPB lab); a Boston University start-up fund and Peter Paul Profession DevelopmentSanders, Jumper, Ackerman, et al. eLife 2021;10:e65962. DOI: ofResearch articleCell BiologyProfessorship (FD); NIH (GM095467 and HL122531 to BDL; GM134949, GM124072, and GM120351 to IL); Volkswagen Foundation (IL); Human Frontiers Science Plan (IL); a Burroughs Wellcome Fund Award for Investigators in Pathogenesis (AP); Longer Life Foundation–RGA/Washington University Collaboration (ASH); postdoctoral fellowship awards from the Uehara Memorial Foundation and JSPS Analysis Fellowships for Young Scientists (TT); from the SENSHIN Health-related Investigation Foundation (S.S); and in the Organic Sciences and Engineering Research Council of Canada (CCJ).Added informationCompeting interests Alex S Holehouse: ASH is actually a consultant for Dewpoint Therapeutics. Clifford P Brangwynne: CPB is a scientific founder and consultant for Nereid Therapeutics. The other Casein Kinase medchemexpress authors declare that no competing interests exist.FundingFunder National Institute of Basic Health-related Sciences National Heart, Lung, and Blood Institute National Institute of General Health-related Sciences National Institute of Basic Medical Sciences Howard Hughes Medical Institute National Institute of Basic Health-related Sciences Grant reference quantity GM095.