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PLoS ONE

PLoS ONE

IF: 2.9
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Screening novel antiviral compounds to treat Clostridioides difficile infections

Published:13 December 2024 DOI: 10.1371/journal.pone.0309624 PMID: 39671442
Brice J Stolz,?Ahmed A Abouelkhair,?Mohamed N Seleem

Abstract

Clostridioides difficile is a major cause of nosocomial infections, often associated with individuals who have gut dysbiosis from previous antibiotic therapies. C. difficile infections (CDI) have a high recurrence rate and impose significant financial and mortality burdens on the healthcare system. Therefore, novel anti-C. difficile drugs are urgently needed to treat and reduce the severity and recurrence of infection. In this study, we screened a library of 618 antiviral drugs to identify a potential candidate for repurposing as novel anti-C. difficile therapeutics. Following our preliminary screening, we identified 9 novel compounds that inhibited C. difficile at a concentration of 16 μM or lower. Among these, 4 antiviral compounds demonstrated the most potent anti-C. difficile activity against a panel of 15 C. difficile isolates, with minimum inhibitory concentrations (MICs) comparable to the drug of choice, vancomycin. These include rottlerin (MIC50 = 0.25 μg/mL), α-mangostin (MIC50 = 1 μg/mL), dryocrassin ABBA (MIC50 = 1 μg/mL), and obefazimod (MIC50 = 4 μg/mL). All exhibited minimal to no activity against representative members of the human gut microbiota. Interestingly, α-mangostin, a natural xanthone derived from the mangosteen fruit, exhibited strong bactericidal action, clearing a high inoculum of C. difficile in less than an hour. All other drugs exhibited bacteriostatic activity. Given their characteristics, these compounds show great promise as novel treatments for CDI.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Mangostin 6147-11-1 C24H26O6 347 suppliers $9.00-$1520.00
Mangostin 6147-11-1 C24H26O6 347 suppliers $9.00-$1520.00
Mangostin 6147-11-1 C24H26O6 347 suppliers $9.00-$1520.00
Mangostin 6147-11-1 C24H26O6 347 suppliers $9.00-$1520.00

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