RT Journal Article
T1 Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome
A1 Xu, Jimin
A1 Berastegui-Cabrera, Judith
A1 Carretero-Ledesma, Marta
A1 Chen, Haiying
A1 Xue, Yu
A1 Wold, Eric A.
A1 Pachón, Jerónimo
A1 Zhou, Jia
A1 Sánchez-Céspedes, Javier
K1 Antiviral agent
K1 Adenovirus
K1 Salicylamide derivatives
K1 Entry inhibition
K1 Antivíricos
K1 Adenoviridae
K1 Endosomas
K1 Infecciones
K1 Virus
K1 Niclosamida
AB Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.
PB MDPI
YR 2021
FD 2021-02-05
LK http://hdl.handle.net/10668/3893
UL http://hdl.handle.net/10668/3893
LA en
NO Xu J, Berastegui-Cabrera J, Carretero-Ledesma M, Chen H, Xue Y, Wold EA, et al. Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome. Int J Mol Sci. 2021 Feb 5;22(4):1617
DS RISalud
RD Apr 6, 2025