人工糖被覆ナノ粒子がCOVID-19感染を阻止(Lab-made sugar-coated particle blocks Covid-19 infection ― Possible new treatment on the horizon)

2025-08-11 スウォンジー大学

<関連情報>

• https://www.swansea.ac.uk/press-office/news-events/news/2025/08/lab-made-sugar-coated-particle-blocks-covid-19-infection–possible-new-treatment-on-the-horizon.php
• https://onlinelibrary.wiley.com/doi/10.1002/smll.202500719

ポリシアルオシドはSARS-CoV-2との結合において硫酸化アナログを上回る Polysialosides Outperform Sulfated Analogs for Binding with SARS-CoV-2

Vinod Khatri, Nico Boback, Hassan Abdelwahab, Daniela Niemeyer, Tahlia M. Palmer, Anil Kumar Sahoo, Yannic Kerkhoff, Kai Ludwig, Julian Heinze, Dilara Balci, Jakob Trimpert, Rainer Haag …
Small  Published: 16 July 2025
DOI:https://doi.org/10.1002/smll.202500719

Abstract

Both polysialosides and polysulfates are known to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. However, a comprehensive site by site analysis of their binding affinities and potential synergistic antiviral effects have not been performed. Here, we report on the synthesis of polysialosides with nanomolar binding affinities to spike proteins of SARS-CoV-2 in solution using microscale thermophoresis. The dendritic polyglycerol based polysialosides dPG₅₀₀SA_0.55 and dPG₅₀₀SA_0.25, with a dissociation constant K_d of 4.78 nm and 10.85 nm, respectively, bind ≈500 times stronger than the high density polysulfated analog dPG₅₀₀S_0.55, to intact SARS-CoV-2 virus particles or isolated spike protein. In fact, the presence of sulfate groups in a heteromultivalent compound dPG₅₀₀SA_0.20S_0.20 weakens the binding to spike proteins. A polycarboxylated analog does not bind to SARS-CoV-2, ruling out that the interaction of polysialoside is simply driven by electrostatics. Using explicit-solvent all-atom molecular dynamics simulations and ensemble docking studies, atomistic details are obtained on the interaction of different functional groups with the SARS-CoV-2 RBD. The data support the conclusion that sialosides interact stronger than sulfates for their binding with RBD of SARS-CoV-2. Notably, the most affine binder dPG₅₀₀SA_0.55 inhibits SARS-CoV-2 (WT, D614G) replication up to 98.6% at 0.5 µm concentrations.