{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:30:26Z","timestamp":1785403826972,"version":"3.56.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The rapid evolution of SARS-CoV-2 variants, driven by antigenic drift in the spike glycoprotein, continues to undermine the efficacy of current vaccines and monoclonal antibody therapies. Targeting conserved features of the spike protein has been a major focus against coronavirus entry and the development of therapeutics. Here, we demonstrate that the plant lectin concanavalin A (ConA) broadly inhibits coronavirus entry through a conserved mechanism. With a combination of cell-cell fusion, pseudoviral entry, and authentic virus infection models, we show that ConA broadly inhibits coronavirus spike-mediated membrane fusion and viral entry. Biochemical analyses reveal that ConA targets two highly conserved N-glycosylation sites outside the receptor binding domain, flanking the S2\u2032 cleavage site via its mannose-binding properties. This interaction sterically impedes proteolytic activation of the spike, a molecular step essential for membrane fusion. ConA exhibited nanomolar efficacy against hCoV-NL63 infections\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and significantly reduced viral load and mitigated lung pathology in hCoV-NL63-infected mice\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Our findings reveal specific N-linked glycosylation sites as a major vulnerability of the spike and highlight ConA as a prototype for the development of lectin-based therapeutics against emerging coronavirus infections.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The rapid evolution of SARS-CoV-2 variants, which evade current vaccines and therapeutics by altering epitopes on the spike protein, highlights a critical need for broad-spectrum antivirals. This study investigates concanavalin A (ConA), a legume lectin that targets highly conserved N-linked glycosylation sites on the spike protein, as a potential pan-coronavirus entry inhibitor. ConA broadly inhibits diverse coronaviruses by blocking spike-mediated membrane fusion. In contrast to previously reported antiviral lectins, ConA binds specifically to high-mannose oligosaccharides by targeting two phylogenetically conserved residues in the S2 subunit outside the receptor-binding domain. Consequently, ConA binding prevents the proteolytic activation of S2\u2032 and effectively inhibits membrane fusion and coronavirus infection both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . This work identifies conserved N-glycosylation sites on the spike protein as stable, vulnerable targets for antiviral intervention, distinct from the variable epitopes recognized by antibodies. These findings indicate that lectins like ConA may provide a promising approach for developing effective antivirals against emerging coronaviruses.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01679-25","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:03:08Z","timestamp":1777280588000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Concanavalin A targets phylogenetically conserved N-linked glycans on coronavirus spike proteins for broad-spectrum antiviral activity"],"prefix":"10.1128","volume":"100","author":[{"given":"Dekuan","family":"Guo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qb7bg95","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese 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