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<p>The human coronavirus HCoV-OC43 (OC43) is the most widespread of the four common cold-causing seasonal coronaviruses, and tissue culture-adapted strains of it have been used for ~50 years. Nevertheless, clinical isolates of OC43 differ from tissue culture-adapted OC43 in ways that call into question the value of the latter as a model. Among these are differences in their entry mechanisms and the activities of their hemagglutinin-esterases (HE). We now show that the spike proteins of OC43 clinical isolates differ from that of the tissue culture-adapted reference strain (OC43-Lab) in their carbohydrate-binding properties and ability to bind mucins, decoy receptors cleaved by the HE. We also show that, unlike HCoV-HKU1 (HKU1), they do not bind with high affinity and specificity the 9-<i>O</i>-acetylated α2–8-linked disialic acid moiety implicated in viral entry for OC43-Lab and HKU1. The spike proteins of the OC43 clinical isolates possess two inserts, not found in OC43-Lab, that flank the carbohydrate-binding site. Our structural analysis of a representative clinical isolate shows that insert-2 is a determinant of these specificity differences and that the carbohydrate-binding site undergoes conformational changes on carbohydrate binding. These structural features are shared by HKU1 and suggest common mechanisms for adaptation to the human sialoglycome.</p>

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OC43 clinical isolate spike proteins have distinct carbohydrate-binding properties

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月16日

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  • Zaky Hassan,
  • Min Jin,
  • Ying Liu,
  • Zhijie Li,
  • Alan H. M. Wong,
  • Marc Desforges,
  • Adam Forman,
  • Mark Nitz,
  • Tarini Gunawardena,
  • Theo J. Moraes,
  • Masahiro Narimatsu,
  • Jeffrey L. Wrana,
  • Hai Yu,
  • Xi Chen,
  • James M. Rini

摘要

The human coronavirus HCoV-OC43 (OC43) is the most widespread of the four common cold-causing seasonal coronaviruses, and tissue culture-adapted strains of it have been used for ~50 years. Nevertheless, clinical isolates of OC43 differ from tissue culture-adapted OC43 in ways that call into question the value of the latter as a model. Among these are differences in their entry mechanisms and the activities of their hemagglutinin-esterases (HE). We now show that the spike proteins of OC43 clinical isolates differ from that of the tissue culture-adapted reference strain (OC43-Lab) in their carbohydrate-binding properties and ability to bind mucins, decoy receptors cleaved by the HE. We also show that, unlike HCoV-HKU1 (HKU1), they do not bind with high affinity and specificity the 9-O-acetylated α2–8-linked disialic acid moiety implicated in viral entry for OC43-Lab and HKU1. The spike proteins of the OC43 clinical isolates possess two inserts, not found in OC43-Lab, that flank the carbohydrate-binding site. Our structural analysis of a representative clinical isolate shows that insert-2 is a determinant of these specificity differences and that the carbohydrate-binding site undergoes conformational changes on carbohydrate binding. These structural features are shared by HKU1 and suggest common mechanisms for adaptation to the human sialoglycome.