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Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro

Viruses. 2021-02; 
Bridget M Hulsebosch, Bryan C Mounce
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DNA Sequencing … N1,N11-Diethylnorspermine (DENSpm; Santa Cruz Biotechnology, Santa Cruz, CA, USA) and Difluoromethylornithine (DFMO; TargetMol, Boston, MA, USA) were diluted to 100× solution (10 mM and 100 mM … Clones were verified for sequencing (GenScript, Piscataway, NJ, USA … Get A Quote

摘要

Enteroviruses, including Coxsackievirus B3 (CVB3), are pervasive pathogens that cause significant disease, including cardiomyopathies. Unfortunately, no treatments or vaccines are available for infected individuals. We identified the host polyamine pathway as a potential drug target, as inhibiting polyamine biosynthesis significantly reduces enterovirus replication in vitro and in vivo. Here, we show that CVB3 is sensitive to polyamine depletion through the polyamine analog diethylnorspermidine (DENSpm), which enhances polyamine catabolism through induction of polyamine acetylation. We demonstrate that CVB3 acquires resistance to DENSpm via mutation of the 2A protease, which enhances proteolytic activity in the... More

关键词

Coxsackievirus, enterovirus, polyamines, protease