{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:54:06Z","timestamp":1782129246900,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,18]]},"group-title":"Microbiology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["CBET 2212779"],"award-info":[{"award-number":["CBET 2212779"]}]},{"name":"National Institutes of Health Human Virome Program","award":["U01DE035632"],"award-info":[{"award-number":["U01DE035632"]}]},{"name":"Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research B","award":["JP26K01072"],"award-info":[{"award-number":["JP26K01072"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Free chlorine reacts with viral proteins, but the protein structural determinants of viral resistance to chlorine treatment remain poorly understood. Here, we curated a dataset of 498 icosahedral virus structures, including intact virions and virus-like particles (VLPs), from the Protein Data Bank. Surprisingly, only 6.6% of these structures are associated with published viral chlorine inactivation rate constants (\n                  <jats:italic>k<\/jats:italic>\n                  <jats:sub>obs<\/jats:sub>\n                  ). In these matched cases representing 12 virus families, total and maximum solvent accessible surface areas (SASA) of methionine residues within viral attachment and entry proteins correlated significantly with median\n                  <jats:italic>k<\/jats:italic>\n                  <jats:sub>obs<\/jats:sub>\n                  (Pearson\u2019s\n                  <jats:italic>r<\/jats:italic>\n                  = 0.83 and 0.45, respectively;\n                  <jats:italic>p<\/jats:italic>\n                  &lt; 0.05), suggesting a critical role of methionine exposure in viral resistance phenotypes. Across the full curated dataset, fuzzy c-means clustering upon total and maximum SASA profiles of chlorine-reactive residues demonstrates that the common surrogate panel (MS2, PhiX174, Phi6, PRD1, and PR772) fails to represent the SASA diversity of human viruses. Instead, VLPs and novel phages may serve as better surrogates for chlorine treatment due to SASA profile similarities to human viruses. Our findings highlight that residue SASA features provide a quantitative baseline for screening viral resistance to chlorine and offer a data-driven strategy to select structurally representative virus surrogates for future disinfection studies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>SYNOPSIS<\/jats:title>\n                  <jats:p>Solvent accessibility of chlorine-reactive residues correlates strongly with viral chlorine resistance, providing a robust quantitative metric to compare chlorine resistance phenotypes across viral capsids.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>TOC<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"732355v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.17.732355","type":"posted-content","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:00:20Z","timestamp":1781852420000},"source":"Crossref","is-referenced-by-count":0,"title":["Solvent accessibility of chlorine-reactive amino acid residues in icosahedral virus structures: A meta-analysis"],"prefix":"10.64898","author":[{"given":"Chonglin","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Civil, Structural and Environmental Engineering, University at Buffalo, Buffalo, New York 14260, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Prinsen","sequence":"additional","affiliation":[{"name":"Department of Civil, Structural and Environmental Engineering, University at Buffalo, Buffalo, New York 14260, United 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