Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

Long, Jason S.; Wright, Edward; Molesti, Eleonora; Temperton, Nigel; Barclay, William

doi:10.12688/f1000research.6085.1

Cited by 49 publications

(41 citation statements)

References 67 publications

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“…Antiviral effects of PPIs on the herpes virus, major-type rhinovirus and minor-type rhinovirus were later confirmed in other studies [30, 31]. Omeprazole and esomeprazole were demonstrated to be able to inhibit the entry of Marburg virus and avian influenza H5 in vitro, but the drug concentrations were too high to achieve in vivo [31]. Rhinovirus (RV) can cause the common cold in adults, and patients with bronchitis, bronchopneumonia or chronic respiratory diseases and infants might be particularly vulnerable to it.…”

Section: Treatment Of Viral and Respiratory System Diseasesmentioning

confidence: 56%

“…A patent registered by Moorman et al demonstrated that PPIs exert an antiviral function by effectively inhibiting virus-specific serine proteases [29]. Antiviral effects of PPIs on the herpes virus, major-type rhinovirus and minor-type rhinovirus were later confirmed in other studies [30, 31]. Omeprazole and esomeprazole were demonstrated to be able to inhibit the entry of Marburg virus and avian influenza H5 in vitro, but the drug concentrations were too high to achieve in vivo [31].…”

Section: Treatment Of Viral and Respiratory System Diseasesmentioning

confidence: 99%

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A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

et al. 2017

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Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.

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Section: Treatment Of Viral and Respiratory System Diseasesmentioning

confidence: 56%

Section: Treatment Of Viral and Respiratory System Diseasesmentioning

confidence: 99%

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

et al. 2017

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“…Ebola virus pseudotypes were produced as previously described [42]. Briefly, 293T/17 cells were transfected with pCMV-Δ8.91, pCSFLW and pCAGGS-EBOV, the latter containing the GP from the Mayinga isolate of Ebola virus (EU224440), in the presence or absence of compound (100 μM).…”

Section: Methodsmentioning

confidence: 99%

Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model

et al. 2016

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The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars.

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“…This resulted in 11 drug screening,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 17 preclinical studies,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 and 9 clinical studies 51, 52, 53, 54, 55, 56, 57, 58, 59…”

Section: Resultsmentioning

confidence: 99%

“…This is believed to take place by inhibiting various factors such as vesicle sorting and endosome-membrane fusion, as well as increasing endosomal pH 27 . Chloroquine was shown to successfully inhibit the Ebola virus in vitro in different studies and with various cell lines 27, 36, 39, 46. Animal studies, on the other hand, revealed mixed results.…”

Section: Discussionmentioning

confidence: 99%

Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review

Sweiti

Ekwunife

Jaschinski

et al. 2017

Current Therapeutic Research

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BackgroundThe Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD.ObjectiveWe aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy.MethodsWe conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial.ResultsWe identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence.ConclusionsSeveral established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.

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Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

Cited by 49 publications

References 67 publications

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model

Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review

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