Rationale for the Evaluation of Fluoxetine in the Treatment of Enterovirus D68-Associated Acute Flaccid Myelitis

Tyler, Kenneth L.

doi:10.1001/jamaneurol.2014.4625

Cited by 53 publications

(47 citation statements)

References 7 publications

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“…Interestingly, these studies also confirmed that fluoxetine, used here as a control, has broader antiviral activity than previously described by us and others (19,36), although its clinical utility might be limited to infections of the central nervous system where it is known to concentrate (12). Detailed analysis of the antimalarial agent mefloquine was discouraging; its modest and somewhat narrow antiviral activity against enteroviruses was associated with a low CC 50 value, yielding a low selectivity index of approximately 6 against CVB3.…”

Section: Discussionsupporting

confidence: 80%

“…All of them were active against representatives of the Enterovirus A and B species; compound 11 also exhibited activity against the two polioviruses tested (Enterovirus C). Since the completion of testing of these compounds against the viruses listed in Table 1, we were able to test the antiviral activity of compound 11 against enterovirus D-68 as well using two isolates recovered in 2014 (8)(9)(10)(11)(12). Compound 11 was highly potent in protecting cells from EV-D68 lysis, having an EC 50 of a few hundred nanomolar and a selective index of Ͼ1,000 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…For example, a new variant of coxsackievirus B1 (CVB1) emerged in the United States in 2007 and was associated with reports of sepsis and myocarditis in newborns at more than 40 locations in the continental United States and Alaska (5,6). Similarly, in 2014, an outbreak of enterovirus D68 (EV-D68), previously likened to rhinoviruses in pathogenicity (7), was responsible for more than 1,100 reports of severe respiratory disease and was linked to more than 100 cases of acute flaccid myelitis (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

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Discovery of Structurally Diverse Small-Molecule Compounds with Broad Antiviral Activity against Enteroviruses

Zuo

Kye

Quinn

et al. 2016

Antimicrob Agents Chemother

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Antiviral drugs do not currently exist for the treatment of enterovirus infections, which are often severe and potentially lifethreatening. We conducted high-throughput molecular screening and identified a structurally diverse set of compounds that inhibit the replication of coxsackievirus B3, a commonly encountered enterovirus. These compounds did not interfere with the function of the viral internal ribosome entry site or with the activity of the viral proteases, but they did drastically reduce the synthesis of viral RNA and viral proteins in infected cells. Sequence analysis of compound-resistant mutants suggests that the viral 2C protein is targeted by most of these compounds. These compounds demonstrated antiviral activity against a panel of the most commonly encountered enteroviruses and thus represent potential leads for the development of broad-spectrum anti-enteroviral drugs.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Discovery of Structurally Diverse Small-Molecule Compounds with Broad Antiviral Activity against Enteroviruses

Zuo

Kye

Quinn

et al. 2016

Antimicrob Agents Chemother

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“…[44–46] Unfortunately, achievable serum concentrations of fluoxetine and its active metabolite norfluoxetine are lower than inhibitory thresholds likely to be required to treat systemic disease [45]; CSF concentrations are higher and hypothetically therapeutic. [47] Similarly, mefloquine exhibits little activity at achievable concentrations. At present, specific antiviral therapy for enteroviruses remains beyond the horizon.…”

Section: Treatment Of Enteroviruses: Recent Progressmentioning

confidence: 99%

Enteroviruses in the early 21st century

Lugo¹,

Krogstad

2016

Current Opinion in Pediatrics

117

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Purpose of review Enteroviruses cause a wide variety of diseases with neurologic, respiratory, skin, and gastrointestinal findings. The purpose of this review is to clarify changes in the classification of enteroviruses, provide information about recent disease outbreaks, and to summarize progress toward treatment and prevention of these infections. Recent findings Enteroviruses are now classified into 4 distinct species. New variants of Coxsackievirus B1, Enterovirus-A71, and Enterovirus-D68 (EV-D68) have emerged as causes of recent outbreaks in the United States and other countries, including more severe disease manifestations than previously described. EV-D68 now commonly circulates in the United States, and has been linked to severe respiratory disease and associated with acute flaccid myelitis. Overcoming enormous political and logistical challenges, fewer than 100 cases of polio have been reported in 2015, and the initiation of “endgame” strategies appears imminent. Unfortunately treatment for enterovirus infections remains supportive, although the recently completed pleconaril trial in newborns suggests that antiviral therapy may reduce mortality in neonatal disease. Summary Clinicians should be aware of the respiratory and neurological manifestations associated with EV-D68 and the potential for severe disease seen with other recently described enterovirus variants. Healthcare professionals should recognize the utility of rapid diagnostic methods and progress toward prevention and treatment of enterovirus infections.

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“…También se han estudiado el itraconazol, mefloquina y nitazoxanida. 15 Ninguna de estas estrategias de tratamiento ha sido evaluada en humanos y se desconoce su verdadera utilidad clínica, 16 por lo que no fueron instauradas en estos pacientes.…”

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