Comparison of the effects of #peramivir and #oseltamivir on the rise in #platelet count in patients with or without proven #influenza (Int J Clin Pharmacol Ther., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Clin Pharmacol Ther. 2018 Dec 11. doi: 10.5414/CP203366. [Epub ahead of print]

Comparison of the effects of peramivir and oseltamivir on the rise in platelet count in patients with or without proven influenza.

Kim YG, Ko SY, Lee SW.

 

Abstract

OBJECTIVE:

Neuraminidase (sialidase) inhibitors are considered to delay platelet clearance through the inhibition of platelet desialylation. A novel neuraminidase inhibitor, peramivir, was recently approved for intravenous administration by the US FDA. We aimed to compare the effects of peramivir and oseltamivir on patient platelet count.

MATERIALS AND METHODS:

Consecutive patients who were treated with peramivir or tested positive for influenza between January 2015 and December 2017 were analyzed. The analysis included 461 patients with platelet counts available; the patients were divided into three groups: patients with proven influenza treated with peramivir (n = 305); those treated with peramivir without proven influenza (n = 83), and those with proven influenza treated with oseltamivir (n = 73).

RESULTS:

Patients treated with peramivir did not show an increase in platelet count from the baseline count, regardless of proven influenza (from 263.4 × 109/L to 267.4 × 109/L; 9 = 0.410) or not (from 257.1 × 109/L to 255.4 × 109/L; p = 0.873); wheeras for patients treated with oseltamivir, a significant increase above the baseline was found (from 223.3 × 109/L to 249.9 × 109/L; p = 0.016), although it was transient.

CONCLUSION:

Peramivir and oseltamivir appear to have different effects on patient platelet count when administered at the recommended doses

PMID: 30526812 DOI: 10.5414/CP203366

Keywords: Seasonal Influenza; Antivirals; Oseltamivir; Zanamivir.

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Intravenous #zanamivir for #influenza #myocarditis and enteral malabsorption (Crit Care, abstract)

[Source: Critical Care, full page: (LINK). Summary, edited.]

Intravenous zanamivir for influenza myocarditis and enteral malabsorption

Fritz-Patrick Jahns, Nawfel Ben-Hamouda, Matthias Kirsch, Aurélien Roumy and Lucas Liaudet

Critical Care, 201822:332 / DOI: https://doi.org/10.1186/s13054-018-2263-y

©  The Author(s). 2018

Received: 26 October 2018 – Accepted: 15 November 2018 – Published: 4 December 2018

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Acute myocarditis is an uncommon complication of influenza with a high mortality [1]. Early therapy with neuraminidase inhibitors (NI) is recommended in patients hospitalized for influenza, notably those with myocarditis. Oral oseltamivir is generally used as the first line NI therapy, whereas parenteral zanamivir and peramivir represent alternatives in selected patients who might not respond to oseltamivir, as may occur in conditions of gut failure and defective enteral drug absorption [2, 3]. We present two patients with influenza myocarditis complicated by enteral drug malabsorption, who received early intravenous zanamivir therapy with excellent clinical outcomes.

(…)

Acknowledgements

None.

Funding

None.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

FPJ, data collection and analysis and writing the manuscript. NBH, data collection and analysis, writing the manuscript, and submission. MK, data collection and analysis and writing the manuscript. AR, data collection and analysis and writing the manuscript. LL, data collection and analysis and writing the manuscript and final revision. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Retrospective collection of data. Standard of care.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Keywords: Seasonal Influenza; Myocarditis; Oseltamivir; Zanamivir; Antivirals.

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Contemporary anti- #Ebola #drug #discovery approaches and platforms (ACS Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

ACS Infect Dis. 2018 Dec 5. doi: 10.1021/acsinfecdis.8b00285. [Epub ahead of print]

Contemporary anti-Ebola drug discovery approaches and platforms.

Schneider-Futschik EK, Hoyer D, Khromykh A, Baell JB, Marsh G, Baker MA, Li J, Velkov T.

 

Abstract

The Ebola virus has a grave potential to destabilise civil society as we know it. The past few deadly Ebola outbreaks were unprecedented in size: the virus spread from the epicentres of Guinea, Sierra Leone, Nigeria and Liberia. The 2014-15 Ebola West Africa outbreak was associated with almost 30,000 suspected or confirmed cases and over 11,000 documented deaths. There is a general acceptance within the World Health Organisation (WHO) and the Ebola outbreak response community that future outbreaks will become increasingly more frequent and more likely to involve inter-continental transmission. The magnitude of the recent outbreaks demonstrated in dramatic fashion the shortcomings of our mass casualty disease response capabilities and lack of therapeutic modalities for supporting Ebola outbreak prevention and control. Currently, there are no approved drugs in sight although vaccines for human Ebola virus infection are in the trial phases. Treatment is limited to pain management and supportive care to counter dehydration and lack of oxygen. This underscores the critical need for effective anti-viral drugs that specifically target this deadly disease. This review examines the current approaches for the discovery of anti-Ebola small molecule or biological therapeutics, their viral targets, mode of action and contemporary platforms, which collectively form the backbone of the anti-Ebola drug discovery pipeline.

PMID: 30516045 DOI: 10.1021/acsinfecdis.8b00285

Keywords: Ebola; Antivirals.

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Duration of #fever and other symptoms after the inhalation of #laninamivir octanoate hydrate in the 2016/17 #Japanese #influenza season; comparison with the 2011/12 to 2015/16 seasons (J Infect Chemother., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect Chemother. 2018 Sep;24(9):718-724. doi: 10.1016/j.jiac.2018.04.013. Epub 2018 Jun 1.

Duration of fever and other symptoms after the inhalation of laninamivir octanoate hydrate in the 2016/17 Japanese influenza season; comparison with the 2011/12 to 2015/16 seasons.

Ikematsu H1, Kawai N2, Iwaki N2, Kashiwagi S2, Ishikawa Y3, Yamaguchi H3, Shiosakai K3.

Author information: 1 Japan Physicians Association, Tokyo, Japan. Electronic address: ikematsu@gray.plala.or.jp. 2 Japan Physicians Association, Tokyo, Japan. 3 Daiichi Sankyo Co., Ltd, Tokyo, Japan.

 

Abstract

The duration of fever and symptoms after laninamivir octanoate hydrate (laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

KEYWORDS: Fever; Influenza; Laninamivir; Neuraminidase inhibitor; Symptom

PMID: 29861186 DOI: 10.1016/j.jiac.2018.04.013 [Indexed for MEDLINE]  Free full text

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Antivirals; Laninamivir; Japan.

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The #Antihistamine Drugs #Carbinoxamine Maleate and #Chlorpheniramine Maleate Exhibit Potent #Antiviral Activity Against a Broad Spectrum of #Influenza Viruses (Front Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Microbiol. 2018 Nov 6;9:2643. doi: 10.3389/fmicb.2018.02643. eCollection 2018.

The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses.

Xu W1, Xia S1, Pu J1, Wang Q1, Li P1, Lu L1, Jiang S1,2.

Author information: 1 Shanghai Public Health Clinical Center and School of Basic Medical Sciences, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, China. 2 Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, United States.

 

Abstract

Influenza A viruses (IAV) comprise some of the most common infectious pathogens in humans, and they cause significant mortality and morbidity in immunocompromised people as well as children and the elderly. After screening an FDA-approved drug library containing 1280 compounds by cytopathic effect (CPE) reduction assay using the Cell Counting Kit-8, we found two antihistamines, carbinoxamine maleate (CAM) and S-(+)-chlorpheniramine maleate (SCM) with potent antiviral activity against A/Shanghai/4664T/2013(H7N9) infection with IC50(half-maximal inhibitory concentration) of 3.56 and 11.84 μM, respectively. Further studies showed that CAM and SCM could also inhibit infection by other influenza A viruses, including A/Shanghai/37T/2009(H1N1), A/Puerto Rico/8/1934(H1N1), A/Guizhou/54/1989(H3N2), and one influenza B virus, B/Shanghai/2017(BY). Mice were challenged intranasally with A/H7N9/4664T/2013 (H7N9) virus and intraperitoneally injected with CAM (10 mg/kg per day) or SCM (1 mg/kg per day) for 5 days. CAM or SCM (10 mg/kg per day) were fully protected against challenge with A/Shanghai/4664T/2013(H7N9). The results from mechanistic studies indicate that both could inhibit influenza virus infection by blocking viral entry into the target cell, the early stage of virus life cycle. However, CAM and SCM neither blocked virus attachment, characteristic of HA activity, nor virus release, characteristic of NA activity. Such data suggest that these two compounds may interfere with the endocytosis process. Thus, we have identified two FDA-approved antihistamine drugs, CAM and SCM, which can be repurposed for inhibiting infection by divergent influenza A strains and one influenza B strain with potential to be used for treatment and prevention of influenza virus infection.

KEYWORDS: antihistamine; carbinoxamine; chlorpheniramine; influenza virus; viral entry

PMID: 30459739 PMCID: PMC6232386 DOI: 10.3389/fmicb.2018.02643

Keywords: Influenza A; Avian Influenza; H7N9; H1N1; H3N2; Antivirals; Carbinoxamine; Chlorpheniramine; Animal models.

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#Genetic characteristics of #hemagglutinin and #neuraminidase of #avian #influenza A (#H7N9) virus in #Guizhou province, 2014-2017 (Zhonghua Liu Xing Bing Xue Za Zhi, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Zhonghua Liu Xing Bing Xue Za Zhi. 2018 Nov 10;39(11):1465-1471. doi: 10.3760/cma.j.issn.0254-6450.2018.11.009.

[Genetic characteristics of hemagglutinin and neuraminidase of avian influenza A (H7N9) virus in Guizhou province, 2014-2017].

[Article in Chinese; Abstract available in Chinese from the publisher]

Wan YH1, Zhuang L, Zheng QN, Ren LJ, Fu L, Jiang WJ, Tang GP, Zhang DZ, Li SJ.

Author information: 1 Guizhou Provincial Center for Disease Control and Prevention, Guiyang 550004, China.

 

Abstract in English, Chinese

Objective:

To understand the molecular characteristics of hemagglutinin (HA) and neuraminidase (NA) as well as the disease risk of influenza virus A H7N9 in Guizhou province.

Methods:

RNAs were extracted and sequenced from HA and NA genes of H7N9 virus strains obtained from 18 cases of human infection with H7N9 virus and 6 environmental swabs in Guizhou province during 2014-2017. Then the variation and the genetic evolution of the virus were analyzed by using a series of bioinformatics software package.

Results:

Homology analysis of HA and NA genes revealed that 2 strains detected during 2014-2015 shared 98.8%-99.2% and 99.2% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Two strains detected in 2016 and 14 strains detected in 2017 shared 98.2%-99.3% and 97.6%-98.8% similarities with vaccine strain A/Hunan/02650/2016, respectively. Other 6 stains detected in 2017 shared 99.1%-99.4% and 98.9%-99.3% similarities with strain A/Guangdong/17SF003/2016, respectively. Phylogenetic analysis showed that all the strains were directly evolved in the Yangtze River Delta evolution branch, but they were derived from different small branch. PEVPKRKRTAR↓GLF was found in 6 of 24 strains cleavage site sequences of HA protein, indicating the characteristic of highly pathogenic avian influenza virus. Mutations A134V, G186V and Q226L at the receptor binding sites were found in the HA. All the strains had a stalk deletion of 5 amino acid residue “QISNT” in NA protein, and drug resistance mutation R294K occurred in strain A/Guizhou-Danzhai/18980/2017. In addition, potential glycosylation motifs mutations NCS42NCT were found in the NA of 9 of 24 strains.

Conclusions:

HA and NA genes of avian influenza A (H7N9) virus showed genetic divergence in Guizhou province during 2014-2017. The mutations of key sites might enhance the virulence of the virus, human beings are more susceptible to it. Hence, the risk of infection is increasing.

KEYWORDS: Avian influenza A (H7N9) virus; Hemagglutinin gene; Molecular characteristic; Neuraminidase gene

PMID:  30462955

Keywords: Avian Influenza; H7N9; Human; China; Guizhou; Antivirals; Drugs Resistance; Oseltamivir; Reassortant strain.

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Efficient #inhibition of #avian and seasonal #influenza A viruses by a virus-specific Dicer-substrate siRNA swarm in human monocyte-derived #macrophages and dendritic cells (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Efficient inhibition of avian and seasonal influenza A viruses by a virus-specific Dicer-substrate siRNA swarm in human monocyte-derived macrophages and dendritic cells

Miao Jiang, Pamela Österlund, Veera Westenius, Deyin Guo, Minna M. Poranen, Dennis H. Bamford, Ilkka Julkunen

DOI: 10.1128/JVI.01916-18

 

ABSTRACT

Influenza A viruses (IAVs) are viral pathogens that cause epidemics and occasional pandemics of significant mortality. The generation of efficacious vaccines and antiviral drugs remains a challenge due to the rapid appearance of new influenza types and antigenic variants. Consequently, novel strategies for the prevention and treatment of IAV infections are needed given the limitations of the presently available antivirals. Here, we used enzymatically produced IAV-specific double-stranded RNA (dsRNA) molecules and Giardia intestinalis Dicer for the generation of a swarm of small interfering RNA (siRNA) molecules. The siRNAs target multiple conserved genomic regions of the IAVs. In mammalian cells, the produced 25–27 nucleotide long siRNA molecules are processed by endogenous Dicer into 21-nucleotide siRNAs and are thus designated as Dicer-substrate siRNAs (DsiRNAs). We evaluated the efficacy of the above DsiRNA swarm at preventing IAV infections in human primary monocyte-derived macrophages and dendritic cells. The replication of different IAV strains, including avian influenza H5N1 and H7N9 viruses, was significantly inhibited by pre-transfection of the cells with the IAV-specific DsiRNA swarm. Up to 7 orders of magnitude inhibition of viral RNA expression was observed, which led to a dramatic inhibition of IAV protein synthesis and virus production. The IAV-specific DsiRNA swarm inhibited virus replication directly through the RNA interference pathway although a weak induction of innate interferon responses was detected. Our results provide direct evidence for the feasibility of the siRNA strategy and the potency of DsiRNA swarms in the prevention and treatment of influenza, including the highly pathogenic avian influenza viruses.

 

IMPORTANCE

In spite of the enormous amount of research, influenza virus is still one of the major challenges for medical virology due to its capacity to generate new variants, which potentially lead to severe epidemics and pandemics. We demonstrated here that a swarm of small interfering RNA (siRNA) molecules, including more than one hundred different antiviral RNA molecules targeting the most conserved regions of influenza A virus genome, could efficiently inhibit the replication of all tested avian and seasonal influenza A variants in human primary monocyte-derived macrophages and dendritic cells. The wide antiviral spectrum makes the virus-specific siRNA swarm a potentially efficient treatment modality against both avian and seasonal influenza viruses.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Influenza A; Avian Influenza.

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