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<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells via its spike (S) protein, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Glycans are thought to influence this interaction by modulating the binding affinity between the S protein and its receptor. In this study, we screened 300 carbohydrate species using a glycan array to identify potential ligands that interact with the S proteins of the Delta and Omicron variants. Among the identified candidates, two aminoglycoside antibiotics, tobramycin and sisomicin, exhibited notable binding to the S protein. Surface plasmon resonance (SPR), circular dichroism (CD), and in silico docking analyses confirmed direct interactions between these aminoglycosides and the S protein, revealing distinct binding characteristics. Nuclear magnetic resonance (NMR) analysis further localized the tobramycin-binding site within the receptor-binding domain (RBD) of the S protein. Tobramycin and sisomicin showed a tendency to inhibit SARS-CoV-2 replication in human induced pluripotent stem cell (hiPSC)-derived lung organoids, though the effect did not reach statistical significance. Docking simulations using the trimeric S model suggested that aminoglycosides bind at an inter-subunit interface. These findings demonstrate that aminoglycosides can directly interact with the SARS-CoV-2 S protein and may serve as scaffolds for developing host-independent antiviral agents against SARS-CoV-2 and its variants.</p>

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Glycan-binding properties of SARS-CoV-2 spike proteins: interactions with aminoglycoside antibiotics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Dai Hatakeyama,
  • Masaki Shoji,
  • Yusuke Miki,
  • Shoji Ueki,
  • Kentaro Yamaguchi,
  • Katsuyuki Nakashima,
  • Yoshiyuki Tanaka,
  • Mariko Yokogawa,
  • Masanori Osawa,
  • Yusuke Kasai,
  • Hiroshi Imagawa,
  • Rina Hashimoto,
  • Kazuo Takayama,
  • Takashi Kuzuhara

摘要

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells via its spike (S) protein, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Glycans are thought to influence this interaction by modulating the binding affinity between the S protein and its receptor. In this study, we screened 300 carbohydrate species using a glycan array to identify potential ligands that interact with the S proteins of the Delta and Omicron variants. Among the identified candidates, two aminoglycoside antibiotics, tobramycin and sisomicin, exhibited notable binding to the S protein. Surface plasmon resonance (SPR), circular dichroism (CD), and in silico docking analyses confirmed direct interactions between these aminoglycosides and the S protein, revealing distinct binding characteristics. Nuclear magnetic resonance (NMR) analysis further localized the tobramycin-binding site within the receptor-binding domain (RBD) of the S protein. Tobramycin and sisomicin showed a tendency to inhibit SARS-CoV-2 replication in human induced pluripotent stem cell (hiPSC)-derived lung organoids, though the effect did not reach statistical significance. Docking simulations using the trimeric S model suggested that aminoglycosides bind at an inter-subunit interface. These findings demonstrate that aminoglycosides can directly interact with the SARS-CoV-2 S protein and may serve as scaffolds for developing host-independent antiviral agents against SARS-CoV-2 and its variants.