Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds

Bernard, Angela M.; Lacroix, Ce ́line; Cabiddu, Maria Grazia; Neyts, Johan; Leyssen, Pieter; Pompei, Raffaello

doi:10.1177/2040206615589035

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…[43] However, clinical experience with these is very limited, and none had significant antiviral activity against the strains of EV-D68 that circulated in 2014. [44] Other novel specific inhibitors of enterovirus have been identified.…”

Section: Treatment Of Enteroviruses: Recent Progressmentioning

confidence: 99%

Enteroviruses in the early 21st century

Lugo¹,

Krogstad

2016

Current Opinion in Pediatrics

127

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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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Section: Treatment Of Enteroviruses: Recent Progressmentioning

confidence: 99%

Enteroviruses in the early 21st century

Lugo¹,

Krogstad

2016

Current Opinion in Pediatrics

127

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“…Results showed that RA inhibited EV71 infection more efficiently when it was present continuously during virus–cell adsorption than if added before adsorption (Fig. 2a and b), as is the case for pleconaril/pirodavir-like anti-EV71 compounds [29]. The highest inhibitory activity of RA occurred during viral infection, at the early stage of EV71 infection (Fig.…”

Section: Discussionmentioning

confidence: 89%

Evaluation of the virucidal effects of rosmarinic acid against enterovirus 71 infection via in vitro and in vivo study

Lin

Jinn

2019

Virol J

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Background Although enterovirus 71 (EV71) is an important public health threat, especially in the Asia-Pacific region, there are still no effective drugs or vaccines to treat and prevent EV71 infection. Therefore, it is critical to develop prophylactic and therapeutic agents against EV71. Rosmarinic acid (RA), a phytochemical, has been discovered to possess a broad spectrum of biological activities. Methods The virucidal effects of RA on EV71 were determined by MTT, western blot, median cell culture infectious dose, apoptosis detection, plaque reduction, semi-quantitative real-time polymerase chain reaction, immunofluorescence detection, molecular docking analysis, and mouse protection assay. Results RA showed a strong protective effect against EV71 infection in human rhabdomyosarcoma cells when the multiplicity of infection was 1, with a low IC 50 value (4.33 ± 0.18 μM) and high therapeutic index (340). RA not only protected cells from EV71-induced cytopathic effects, but also from EV71-induced apoptosis. The results of time-of-addition analysis demonstrated that the inhibitory activity of RA was highest at the early stage of viral infection. Consistent with this, the infectivity of EV71 in the early stage of viral infection also was observed to be limited in neonatal mice treated with RA. Further, molecular docking predicts that RA could replace the natural pocket factor within the VP1 capsid-binding hydrophobic pocket. Conclusions This study suggests that RA has the potential to be developed as an antiviral agent against initial EV71 infection to prevent or reduce EV71-induced pathogenesis and complications, since RA can effectively reduce EV71 infection in the early stages of viral infection.

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“…Despite promising in vitro results, the two well-known pocket binders pleconaril and vapendavir ( Figure 2 ), have failed the clinical trials due to their low efficacy and several side effects. Nevertheless, their discovery raised interest in the search for analogues [ 14 , 15 ].…”

Section: Direct-acting Antiviralsmentioning

confidence: 99%

“…Bernard et al studied CV-B3 and echovirus inhibitors and found that compound 6501 ( Figure 3 ) was active with an EC 50 of 11 µM [ 14 ].…”

Section: Direct-acting Antiviralsmentioning

confidence: 99%

Direct-Acting Antivirals and Host-Targeting Approaches against Enterovirus B Infections: Recent Advances

et al. 2023

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Enterovirus B (EV-B)-related diseases, which can be life threatening in high-risk populations, have been recognized as a serious health problem, but their clinical treatment is largely supportive, and no selective antivirals are available on the market. As their clinical relevance has become more serious, efforts in the field of anti-EV-B inhibitors have greatly increased and many potential antivirals with very high selectivity indexes and promising in vitro activities have been discovered. The scope of this review encompasses recent advances in the discovery of new compounds with anti-viral activity against EV-B, as well as further progress in repurposing drugs to treat these infections. Current progress and future perspectives in drug discovery against EV-Bs are briefly discussed and existing gaps are spotlighted.

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Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds

Cited by 10 publications

References 17 publications

Enteroviruses in the early 21st century

Enteroviruses in the early 21st century

Evaluation of the virucidal effects of rosmarinic acid against enterovirus 71 infection via in vitro and in vivo study

Direct-Acting Antivirals and Host-Targeting Approaches against Enterovirus B Infections: Recent Advances

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