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Open AccessArticle

Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome

1
Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA
2
Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío, CSIC, University of Seville, E41013 Seville, Spain
3
Department of Medicine, University of Seville, E-41009 Seville, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Li Lin and Kamalendra Singh
Int. J. Mol. Sci. 2021, 22(4), 1617; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041617
Received: 2 January 2021 / Revised: 26 January 2021 / Accepted: 2 February 2021 / Published: 5 February 2021
(This article belongs to the Special Issue Virus Replication)
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. View Full-Text
Keywords: antiviral agent; adenovirus; salicylamide derivatives; entry inhibition antiviral agent; adenovirus; salicylamide derivatives; entry inhibition
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MDPI and ACS Style

Xu, J.; Berastegui-Cabrera, J.; Carretero-Ledesma, M.; Chen, H.; Xue, Y.; Wold, E.A.; Pachón, J.; Zhou, J.; Sánchez-Céspedes, J. Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome. Int. J. Mol. Sci. 2021, 22, 1617. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041617

AMA Style

Xu J, Berastegui-Cabrera J, Carretero-Ledesma M, Chen H, Xue Y, Wold EA, Pachón J, Zhou J, Sánchez-Céspedes J. Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome. International Journal of Molecular Sciences. 2021; 22(4):1617. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041617

Chicago/Turabian Style

Xu, Jimin; Berastegui-Cabrera, Judith; Carretero-Ledesma, Marta; Chen, Haiying; Xue, Yu; Wold, Eric A.; Pachón, Jerónimo; Zhou, Jia; Sánchez-Céspedes, Javier. 2021. "Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome" Int. J. Mol. Sci. 22, no. 4: 1617. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041617

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