Salicylamide Derivatives Inhibit Multiple Picornavirus Infections through Early Endosome Neutralization
- 1Shenzhen Campus of Sun Yat-sen University , , , Guangdong ,
Abstract
The global resurgence of picornaviruses highlights an urgent need for broad-spectrum antivirals. Here, we screened 102 salicylamide derivatives, identifying HJW1107 and CZY1111 as inhibitors with submicromolar IC50 values. Time-of-addition and RNA transfection assays confirmed that these derivatives target early infection stages rather than virus replication or assembly. Mechanistically, HJW1107 and CZY1111 exhibit protonophore-like activity that neutralizes endosomal acidification, trapping internalized virions within EEA1-positive early endosomal compartments. This arrest prevents pH-dependent viruses from undergoing uncoating after endocytosis required for virus replication. These results demonstrate that optimizing the salicylamide scaffold to disrupt endosomal maturation offers a therapeutic strategy against acidification-dependent picornaviruses, potentially imposing a higher barrier to resistance than direct targeting of highly variable viral proteins.
Related
- Simplified removal of Fe(II) and Mn(II) from groundwater via oxidative coprecipitation with portlandite and subsequent neutralization with CO2 bubbling
- Recyclable Synthetic Polymer Nanoparticles for Sustained Target Neutralization
- Synthesis of N-Protected L-DOPA(acetonide) Derivatives
- Swapping O for S: Converting Oxetanes into Thietanes and their Oxidized Derivatives
- ePC-SAFT: an electrolyte equation-of-state engine with exact derivatives for phase and reaction equilibrium and parameter estimation
BibTeX
@article{fang2026salicylamide,
title = {{Salicylamide Derivatives Inhibit Multiple Picornavirus Infections through Early Endosome Neutralization}},
author = {Yiqun Fang and Ziyin Cai and Zhipeng Zhang and Nuo Xu and Xinhui Qiu and Jimin Xu and Hongbing Jiang},
journal = {ACS Omega},
year = {2026},
month = nov,
doi = {10.1021/acsomega.6c09148},
url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c09148/5466303/Salicylamide-Derivatives-Inhibit-Multiple},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Salicylamide Derivatives Inhibit Multiple Picornavirus Infections through Early Endosome Neutralization
AU - Yiqun Fang
AU - Ziyin Cai
AU - Zhipeng Zhang
AU - Nuo Xu
AU - Xinhui Qiu
AU - Jimin Xu
AU - Hongbing Jiang
PY - 2026
DA - 2026/11/09
JO - ACS Omega
DO - 10.1021/acsomega.6c09148
UR - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c09148/5466303/Salicylamide-Derivatives-Inhibit-Multiple
AB - The global resurgence of picornaviruses highlights an urgent need for broad-spectrum antivirals. Here, we screened 102 salicylamide derivatives, identifying HJW1107 and CZY1111 as inhibitors with submicromolar IC50 values. Time-of-addition and RNA transfection assays confirmed that these derivatives target early infection stages rather than virus replication or assembly. Mechanistically, HJW1107 and CZY1111 exhibit protonophore-like activity that neutralizes endosomal acidification, trapping internalized virions within EEA1-positive early endosomal compartments. This arrest prevents pH-dependent viruses from undergoing uncoating after endocytosis required for virus replication. These results demonstrate that optimizing the salicylamide scaffold to disrupt endosomal maturation offers a therapeutic strategy against acidification-dependent picornaviruses, potentially imposing a higher barrier to resistance than direct targeting of highly variable viral proteins.
SN - 2470-1343
ER -