tetano
Editor, Senior Moderator
Carbohydr Res
. 2023 Aug 4;532:108918.
doi: 10.1016/j.carres.2023.108918. Online ahead of print. Preparation of eicosavalent triazolylsialoside-conjugated human serum albumin as a dual hemagglutinin/neuraminidase inhibitor and virion adsorbent for the prevention of influenza infection
Yang Li[SUP] 1 [/SUP], Han-Yu Liu[SUP] 1 [/SUP], Ming-Jiang Yang[SUP] 1 [/SUP], Dong Liu[SUP] 1 [/SUP], Jia-Qi Song[SUP] 1 [/SUP], Zhiqi Lao[SUP] 2 [/SUP], Yue Chen[SUP] 3 [/SUP], Yang Yang[SUP] 4 [/SUP]
Affiliations
A triazolylsialoside-human serum albumin conjugate was prepared as a multivalent hemagglutinin and neuraminidase inhibitor using a di-(N-succinimidyl) adipate strategy. Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) indicated that five tetravalent sialyl galactosides were grafted onto the protein backbone resulting in an eicosavalent triazolylsialoside-protein complex. Compared with monomeric sialic acid, molecular interaction studies showed that the synthetic pseudo-glycoprotein bound tightly not only to hemagglutinin (HA)/neuraminidase (NA) but also to mutated drug-resistant NA on the surface of the influenza virus with a dissociation constant (K[SUB]D[/SUB]) in the 1 μM range, attributed to the cluster effect. Moreover, this glycoconjugate exhibited potent antiviral activity against a broad spectrum of virus strains and showed no cytotoxicity towards Human Umbilical Vein Endothelial Cells (HUVECs) and Madin-Darby canine kidney (MDCK) cells at high concentrations. Further mechanistic studies demonstrated this multivalent sialyl conjugate showed strong capture and trapping of influenza virions, thus disrupting the ability of the influenza virus to infect host cells. This research lays the experimental foundation for the development of new antiviral agents based on multivalent sialic acid-protein conjugates.
Keywords: Human serum albumin conjugate; Influenza hemagglutinin/neuraminidase inhibitor; Multivalent sialoside; Surface plasmon resonance.
. 2023 Aug 4;532:108918.
doi: 10.1016/j.carres.2023.108918. Online ahead of print. Preparation of eicosavalent triazolylsialoside-conjugated human serum albumin as a dual hemagglutinin/neuraminidase inhibitor and virion adsorbent for the prevention of influenza infection
Yang Li[SUP] 1 [/SUP], Han-Yu Liu[SUP] 1 [/SUP], Ming-Jiang Yang[SUP] 1 [/SUP], Dong Liu[SUP] 1 [/SUP], Jia-Qi Song[SUP] 1 [/SUP], Zhiqi Lao[SUP] 2 [/SUP], Yue Chen[SUP] 3 [/SUP], Yang Yang[SUP] 4 [/SUP]
Affiliations
- PMID: 37586142
- DOI: 10.1016/j.carres.2023.108918
A triazolylsialoside-human serum albumin conjugate was prepared as a multivalent hemagglutinin and neuraminidase inhibitor using a di-(N-succinimidyl) adipate strategy. Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) indicated that five tetravalent sialyl galactosides were grafted onto the protein backbone resulting in an eicosavalent triazolylsialoside-protein complex. Compared with monomeric sialic acid, molecular interaction studies showed that the synthetic pseudo-glycoprotein bound tightly not only to hemagglutinin (HA)/neuraminidase (NA) but also to mutated drug-resistant NA on the surface of the influenza virus with a dissociation constant (K[SUB]D[/SUB]) in the 1 μM range, attributed to the cluster effect. Moreover, this glycoconjugate exhibited potent antiviral activity against a broad spectrum of virus strains and showed no cytotoxicity towards Human Umbilical Vein Endothelial Cells (HUVECs) and Madin-Darby canine kidney (MDCK) cells at high concentrations. Further mechanistic studies demonstrated this multivalent sialyl conjugate showed strong capture and trapping of influenza virions, thus disrupting the ability of the influenza virus to infect host cells. This research lays the experimental foundation for the development of new antiviral agents based on multivalent sialic acid-protein conjugates.
Keywords: Human serum albumin conjugate; Influenza hemagglutinin/neuraminidase inhibitor; Multivalent sialoside; Surface plasmon resonance.