Synthesis of new compounds with promising antiviral properties against group A and B Human Rhinoviruses

Bernard, Angela M.; Cabiddu, Maria Grazia; Montis, Stefania De; Mura, R.; Pompei, Raffaello

doi:10.1016/j.bmc.2014.05.066

Cited by 8 publications

(18 citation statements)

References 25 publications

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“…Vapendavir (Biota Holdings), a benzisoxazole analogue of pirodavir, is currently in clinical development for the treatment of rhinovirus-induced asthma exacerbations [ 9 ]. In the past, we explored the antiviral activity of a panel of pirodavir analogues with modifications of the central hydrocarbon chain [ 10 , 11 ]. Here, we report on the particular characteristics of the antiviral activity and mode of action of a novel and the until now most potent and least toxic analogue in this series (Fig.…”

Section: Body Of Textmentioning

confidence: 99%

In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses

Lacroix

Laconi

Angius

et al. 2015

Virol J

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BackgroundRhinovirus infections do not only cause common colds, but may also trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Even though rhinoviruses have been the focus of extensive drug development efforts in the past, an anti-rhinoviral drug still has to make it to the market. In the past, the viral capsid protein VP1 has been shown to be an important target for the development of antiviral molecules. Furthermore, many different chemical scaffolds appear to possess the properties that are required to inhibit virus replication by this mechanism of action. I-6602, an analogue of the rhinovirus inhibitor pirodavir, was previously identified as a potent inhibitor of rhinovirus infection. Here, we describe the antiviral activity of its analogue ca603, a molecule with a modified linker structure, and corroborate its mechanism of action as a capsid binder.FindingsThe molecule ca603 shows antiviral activity against a panel of rhino-and enteroviruses. Cross-resistance is observed against viruses with mutations that render them resistant to the inhibitory effect of the capsid binder pleconaril and thermostability assays demonstrate that the compound binds and stabilizes the viral capsid. Binding of the molecule to the VP1 protein is corroborated by in silico modeling.ConclusionsIt is confirmed that ca603 inhibits rhinovirus replication by interaction with the VP1 protein and, by this, allows to further expand the chemical diversity of capsid-binding molecules.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0330-4) contains supplementary material, which is available to authorized users.

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Section: Body Of Textmentioning

confidence: 99%

In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses

Lacroix

Laconi

Angius

et al. 2015

Virol J

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“…While several drugs with in vitro activity against human rhinovirus, the leading cause of CC (Mäkelä et al., 1998), are currently under investigation (Bernard et al., 2014; MacLeod et al., 2013; Mello et al., 2014), there are yet no licensed effective antivirals for this condition, and therefore treatment aiming at symptom relief, a shortening of the illness duration, and a reduction of the risk of complications as well as of the infectivity to others remains the standard recommendation (Arroll, 2011; Picon et al., 2013). Symptomatic treatments of CC, including antihistamines, decongestants, non-steroidal anti-inflammatory drugs, paracetamol, and phyto-pharmaceutical products, have been extensively reviewed (Allan and Arroll, 2014; Arroll, 2011; Hemilä and Chalker, 2013; Kim et al., 2009; Mossad, 1998; Nahas and Balla, 2011; Science et al., 2012; Simasek and Blandino, 2007), albeit without providing clear, universally accepted therapeutic recommendations.…”

Section: Introductionmentioning

confidence: 99%

Treatment of signs and symptoms of the common cold using EPs 7630 - results of a meta-analysis

Schapowal¹,

Dobos

Cramer

et al. 2019

Heliyon

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The efficacy of Pelargonium sidoides preparation EPs 7630 in the common cold (CC) was assessed by performing meta-analyses of randomized, double-blind, placebo-controlled trials. Mean differences (MD) and risk ratios (RR) with their 95% confidence intervals (CI) were computed. Five trials with a total of 833 patients were included. All trials had a treatment period of ten days with visits at days 3, 5, and 10 after baseline and used a ten-symptom Cold Intensity Score (CIS) as the primary outcome. Significant differences favoring EPs 7630 were observed for total CIS reduction (day 5: MD = -2·30; 95%CI = -4·12,-0·49; day 10: MD = -1·16; 95%CI = -2·22,-0·10), proportion of patients with substantial improvement (day 5: RR = 1·73; day 10: RR = 1·06) and complete remission (day 5: RR = 2·52; day 10: RR = 2·13). Subjects treated with EPs 7630 missed fewer days at work, used less paracetamol and had an improved sleep quality. No serious adverse reactions to EPs 7630 were reported. The results support the efficacy of EPs 7630 in adults with CC.

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“…The synthesis and chemical properties of the molecules of the series [6c-10c] were previously described by Bernard et al, 14 and also by Laconi et al 15 for those of series [6002-6702]. Pleconaril was kindly provided by V. Makarov (RAS, Institute of Biochemistry, Russia).…”

Section: Methodsmentioning

confidence: 99%

“…13 We have previously described a panel of novel compounds [6c-10c], which were developed based on the core structure of both pleconaril and pirodavir with substantial modifications in the central hydrocarbon chain and the pyridazinyl-piperidinyl moiety (see supplemental material for chemical data). 14 …”

Section: Introductionmentioning

confidence: 99%

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

Bernard

Lacroix

Cabiddu

et al. 2015

Antivir Chem Chemother

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Background: The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. Methods: These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Results: Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cellprotective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC 50 ) as low as 0.3 mM (Selectivity index or SI ¼ 483), and selectivity indexes greater than 857 (EC 50 ¼ 0.6 mM) and 1524 (EC 50 ¼ 0.33 mM). Conclusion: Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs.

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Synthesis of new compounds with promising antiviral properties against group A and B Human Rhinoviruses

Cited by 8 publications

References 25 publications

In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses

In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses

Treatment of signs and symptoms of the common cold using EPs 7630 - results of a meta-analysis

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

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