Ezzatpour S, Thakur K, Erzoah Ndede K et al. Sci Adv. 2025 Aug 29;11(35):eady3554. doi: 10.1126/sciadv.ady3554. Epub 2025 Aug 27. Abstract
Viral pandemics continue to threaten global health and economic stability. Despite medical advances, the absence of broad-spectrum antivirals (BSAs) prevents rapid responses to emerging viral threats. This is largely due to the lack of universal drug targets across diverse viral families and high variability among viral proteins. In this study, we evaluated 57 synthetic carbohydrate receptors (SCRs) for antiviral activity in cellulo using pseudotyped virus particles (PVPs) from six high-risk viruses across three families: Paramyxoviridae, Filoviridae, and Coronaviridae.
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| Binding of SCRs to N-glycan microarrays |
Four SCRs inhibited all tested PVPs, and their efficacy was confirmed against live viruses including SARS-CoV-2, MERS-CoV, EBOV, MARV, NiV, and HeV. Notably, SCR005 and SCR007, which exhibited minimal toxicity, significantly reduced SARS-CoV-2 infection in a severe animal model with a single dose. Mechanistic studies suggested that SCRs bind viral envelope N-glycans, blocking viral attachment and/or fusion. These results identify conserved viral N-glycans as promising BSA targets and establish SCRs as candidate prophylactic agents against enveloped viruses with pandemic potential.PDF
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