TY - JOUR
T1 - Broad-spectrum Synthetic Carbohydrate Receptors (SCRs) Inhibit Viral Entry Across Multiple Virus Families
AU - Ezzatpour, Shahrzad
AU - Thakur, Khushabu
AU - Ndede, Kenneth Erzoah
AU - Buchholz, David W
AU - Choi, Annette
AU - Imbiakha, Brian
AU - Carter, Jordan
AU - Onofrei, David
AU - Eaton, Brett Parker
AU - Postnikova, Elena
AU - Murphy, Michael
AU - Tapia, Beicer C.
AU - Bello, Diana
AU - Pasari, Siddharth
AU - Russo, Anthony
AU - Babayev, Matthew
AU - Holland, Gregory P
AU - Holbrook, Michael R
AU - Caddy, Sarah
AU - Moran, Steven J.
AU - Davachi, Seyed Mohammad
AU - Monreal, Isaac Abrrey
AU - Sahler, Julie
AU - Ortega, Victoria
AU - Miranda, Jose M.
AU - Whittaker, Gary R.
AU - Jager, Mason Cameron
AU - Bhagwat, Seema K.
AU - Chopra, Pradeep
AU - Boons, Geert-Jan
AU - Marianski, Mateusz
AU - Braunschweig, Adam B.
AU - Aguilar, Hector C.
N1 - Publisher Copyright:
© 2025 The Authors, some rights reserved;
PY - 2025/8
Y1 - 2025/8
N2 - 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. 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.
AB - 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. 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.
U2 - 10.1126/sciadv.ady3554
DO - 10.1126/sciadv.ady3554
M3 - Article
SN - 2375-2548
VL - 11
JO - Science advances
JF - Science advances
IS - 35
M1 - eady3554
ER -