2. Academic Validation
  3. Glycan-binding properties of SARS-CoV-2 spike proteins: interactions with aminoglycoside antibiotics

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

  • Sci Rep. 2026 Mar 9;16(1):12769. doi: 10.1038/s41598-026-42404-3.
Dai Hatakeyama 1 2,  Masaki Shoji 1,  Yusuke Miki 1,  Shoji Ueki 3,  Kentaro Yamaguchi 3,  Katsuyuki Nakashima 1,  Yoshiyuki Tanaka 1,  Mariko Yokogawa 4,  Masanori Osawa 4,  Yusuke Kasai 1,  Hiroshi Imagawa 1,  Rina Hashimoto 5 6,  Kazuo Takayama 5 6,  Takashi Kuzuhara 7
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
  • 2 Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan.
  • 3 Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Takamatsu, Japan.
  • 4 Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan.
  • 5 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • 6 Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
  • 7 Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. [email protected].
PMID: 41803230 DOI: 10.1038/s41598-026-42404-3
Abstract

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.

Keywords

Aminoglycoside antibiotics; Glycan array; SARS-CoV-2; Sisomicin; Spike protein; Tobramycin.

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