Bisacodyl Limits Chikungunya Virus Replication
            <i>In Vitro</i>
            and Is Broadly Antiviral

LoMascolo, Natalie J; Cruz-Pulido, Yazmin E.; Mounce, Bryan C.

doi:10.1128/aac.00292-22

Antimicrob Agents Chemother

2022

DOI: 10.1128/aac.00292-22

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Bisacodyl Limits Chikungunya Virus Replication In Vitro and Is Broadly Antiviral

Natalie J LoMascolo

Yazmin E. Cruz-Pulido

Bryan C. Mounce

Abstract: Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral identification and development. Developing antivirals requires years of research and validation, and recent outbreaks have highlighted the need for preparedness in counteracting pandemics.

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2024

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Cited by 1 publication

References 44 publications

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Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection

Villanueva Guzman,

LoMascolo,

May

et al. 2024

ACS Infect. Dis.

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Enteroviruses cause significant morbidity and mortality worldwide, and Coxsackievirus B3 (CVB3) is one of the most commonly reported. Coxsackieviruses establish persistent infection, characterized as infection that is not cleared from host cells generating a continuous infection. No antivirals targeting persistent or acute infection are available, and CVB3 may respond differently depending on the type of infection. Therefore, there is an urgent need for new antiviral drugs to combat acute and persistent CVB3 infection. We developed a system to study persistent CVB3 infection with pancreatic ductal cell line PANC-1, and we used an epithelial cell line, Vero-E6 cells, to study acute CVB3 infection. We maintained persistently infected cells for over a year. Now, in an effort to identify antivirals, using the National Institutes of Health's Developmental Therapeutics Program (DTP), we screened thousands of compounds for activity against acute and persistent CVB3 infection, and among the hits was Ro 5−3335, a 1,4-benzodiazepine nordazepam that acts as a RUNX1-CBFβ leukemia inhibitor. Ro 5−3335 has previously been reported to inhibit HIV-1 gene expression through interference with Tatmediated transactivation. We confirmed Ro 5−3335's antiviral activity against CVB3 in both acute and persistent infection, in several cell types and at pharmacologically favorable conditions. We show that Ro 5−3335 has minimal cytotoxicity and is antiviral over several rounds of replication. We identified viral egress as a putative target. We also show efficacy against other RNA viruses, but it is ineffective against a model DNA virus. Overall, Ro 5−3335 is a promising antiviral that may target CVB3 infection.

show abstract

Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection

Villanueva Guzman,

LoMascolo,

May

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

show abstract

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Bisacodyl Limits Chikungunya Virus Replication In Vitro and Is Broadly Antiviral

Cited by 1 publication

References 44 publications

Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection

Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection

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