tetano
Editor, Senior Moderator
Sci Rep
. 2026 Mar 9.
doi: 10.1038/s41598-026-42404-3. Online ahead of print.
Glycan-binding properties of SARS-CoV-2 spike proteins: interactions with aminoglycoside antibiotics
Dai Hatakeyama[SUP] 1 2 [/SUP], Masaki Shoji[SUP] 1 [/SUP], Yusuke Miki[SUP] 1 [/SUP], Shoji Ueki[SUP] 3 [/SUP], Kentaro Yamaguchi[SUP] 3 [/SUP], Katsuyuki Nakashima[SUP] 1 [/SUP], Yoshiyuki Tanaka[SUP] 1 [/SUP], Mariko Yokogawa[SUP] 4 [/SUP], Masanori Osawa[SUP] 4 [/SUP], Yusuke Kasai[SUP] 1 [/SUP], Hiroshi Imagawa[SUP] 1 [/SUP], Rina Hashimoto[SUP] 5 6 [/SUP], Kazuo Takayama[SUP] 5 6 [/SUP], Takashi Kuzuhara[SUP] 7 [/SUP]
Affiliations
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.
. 2026 Mar 9.
doi: 10.1038/s41598-026-42404-3. Online ahead of print.
Glycan-binding properties of SARS-CoV-2 spike proteins: interactions with aminoglycoside antibiotics
Dai Hatakeyama[SUP] 1 2 [/SUP], Masaki Shoji[SUP] 1 [/SUP], Yusuke Miki[SUP] 1 [/SUP], Shoji Ueki[SUP] 3 [/SUP], Kentaro Yamaguchi[SUP] 3 [/SUP], Katsuyuki Nakashima[SUP] 1 [/SUP], Yoshiyuki Tanaka[SUP] 1 [/SUP], Mariko Yokogawa[SUP] 4 [/SUP], Masanori Osawa[SUP] 4 [/SUP], Yusuke Kasai[SUP] 1 [/SUP], Hiroshi Imagawa[SUP] 1 [/SUP], Rina Hashimoto[SUP] 5 6 [/SUP], Kazuo Takayama[SUP] 5 6 [/SUP], Takashi Kuzuhara[SUP] 7 [/SUP]
Affiliations
- PMID: 41803230
- DOI: 10.1038/s41598-026-42404-3
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.