Xu, JiminBerastegui-Cabrera, JudithCarretero-Ledesma, MartaChen, HaiyingXue, YuWold, Eric A.Pachón, JerónimoZhou, JiaSánchez-Céspedes, Javier2022-08-092022-08-092021-02-05Xu 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):1617http://hdl.handle.net/10668/3893Human 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Antiviral agentAdenovirusSalicylamide derivativesEntry inhibitionAntivíricosAdenoviridaeEndosomasInfeccionesVirusNiclosamidaMedical Subject Headings::Organisms::Viruses::DNA Viruses::Adenoviridae::Mastadenovirus::Adenoviruses, HumanMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral AgentsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug DiscoveryMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::EndosomesMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Transformed::HEK293 CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Anilides::Salicylanilides::NiclosamideMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::SalicylamidesMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Small Molecule LibrariesMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Viral TropismMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Virus Physiological Phenomena::Virus Physiological Processes::Virus InternalizationMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Virus Replicationresearch article33562748open access10.3390/ijms220416171422-0067PMC7915867