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Aim: Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and paediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provide a baseline risk assessment and identify gaps for targeted investigation., Methods: Clinical trials have been searched and reviewed; 23 repurposed drugs and drug combinations and nine candidate vaccines have been assessed regarding the availability of relevant data in paediatrics and pregnant women and to evaluate expected or unanticipated risk., Results: Thirteen of the repurposed drugs or drug combinations are indicated for use in paediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have paediatric subgroups been planned for enrolment. Data from individual case studies and RWD may suggest that subpopulations of both paediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state., Conclusion: In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in paediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications., (© 2020 British Pharmacological Society.)

Background: The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies., Aim: To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection., Methods: We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses., Results: Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon., Conclusions: Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults., (© 2020 John Wiley & Sons Ltd.)

Lists the forthcoming research articles published in the September 15, 1992 issue of the "European Journal of Biochemistry." "Stoichiometry of interaction between interferon y and its receptor" by M. Fountoulakis, M. Zulauf, A. Lustig and G. Garotta; "Leukotriene uptake by hepatocytes and hepatoma cells" by I. Leier, M. Muller, G. Jedlitschky and D. Keppler; "Regulation of insulin-like-growth-factor-II gene expression in rat liver cells" R. Zarrilli, V. Colantouni and C. B. Bruni; "NMR study of the solution conformation of actionmycin D," by C. Yu, Y.-Y. Tseng.

Presents a list of studies that will be submitted to forthcoming issues of the "European Journal of Biochemistry." "Structures of the major carbohydrates of natural human interleukin-2"; "Differential regulation of interferon-induced mRNAs and e-myc mRNA by alpha and gamma-interferons"; "Synthesis, transport and processing of cathepsin C in Morris hepatoma 7777 cells and rat hepatocytes."

Background: Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare. Multiple compounds are under investigation., Aims: To describe the pharmacology, including drug interactions, efficacy, safety and mechanisms of action of investigational compounds for HBV infection., Methods: Descriptive review using PubMed and Google to identify literature/conference papers on investigational compounds (≥Phase 2) with data on efficacy and safety in HBV-infected patients., Results: Bulevirtide, JNJ-56136379, ABI-H0731, REP-2139, and inarigivir decrease HBV DNA/RNA, with greater potency than current nucleos(t)ide analogues. REP-2139 (25%-75% of patients, 20-48 weeks treatment) and inarigivir (26% of patients, 12-24 weeks treatment) induce HBsAg loss. ARO-HBV reduced (>1.5 log 10 UI/mL) HBsAg in 85% of patients (12 weeks treatment). There are some safety concerns with investigational agents (e.g., increased bile acids with bulevirtide, and liver enzyme flares with REP-2139) which will require a risk benefit assessment compared with current therapies. Single and multidose pharmacokinetic data are available for bulevirtide, JNJ-56136379, ABI-H0731; no such data are available for REP-2139, ARO-HBV, inarigivir. Initial drug interaction assessments have been performed with bulevirtide and inarigivir (only in vitro)., Conclusions: There are promising investigational therapies for HBV infection. Increasing the potential for HBsAg loss may result in more patients achieving functional cure. However, many knowledge gaps remain such as pharmacokinetics in those with HBV, cirrhosis and renal impairment but also the interaction potential between investigational therapies, risk-benefit profiles, and potential for drug interactions with medications used to treat comorbidities associated with aging., (© 2019 John Wiley & Sons Ltd.)

Presents several research related to immunology published in the 2005 issue of the "Immunology." "Putting the NK Cell in its Place," by Geraldine O'Connor, Orla Hart and Clair Gardiner; "TLR Against Poly(I:C)-induced Antiviral Response in Human Corneal Epithelial Cells," by Ashok Kumar, Jing Zhang and Fu-Shin Yu; "Characterization of a Novel PMA-inducible Pathway of IL-13 Gene Regulation in T-cells," by A. Cianferoni, G. Floria, J. Guo, R. Chen, M. Wills-Karp, V. Casolaro and S. N. Georas.

LINKED CONTENT: This article is linked to Farina et al paper. To view this article, visit https://doi.org/10.1111/apt.17463 [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al papers. To view these articles visit https://doi.org/10.1111/apt.13774 and https://doi.org/10.1111/apt.13849. [ABSTRACT FROM AUTHOR]

Background: Children continue to suffer from the impact of the human immunodeficiency virus‐acquired immunodeficiency syndrome (HIV/AIDS) pandemic. In Cape Town, these children receive medical care including antiretroviral therapy from facilities like Tygerberg Hospital's Paediatric Infectious Diseases Clinic. HIV‐infected children may experience an increased caries experience when compared with their healthy peers. Aim: The aim of this study was to determine the oral health status of HIV‐infected children younger than 12 years receiving antiviral drugs at the Paediatric Infectious Diseases Clinic. Design A cross‐sectional survey was conducted among children aged between 2 and 12 years presenting at this clinic. Caregivers were interviewed to obtain information regarding health seeking behaviour, oral hygiene practices and dietary habits. A single clinician undertook a standardized clinical intraoral examination according to the World Health Organization guidelines, with modifications. Results: Sixty‐six children were recruited. A high prevalence of dental caries (78.8%) and an unmet treatment need of 90.4% were recorded among the participants. Most children had never visited the dentist, and those who did had mainly received emergency dental care. Conclusion: The high prevalence of severe dental caries in this population highlights the need for oral health awareness and the inclusion of oral health care in the comprehensive care of children with HIV. Why this paper is important to paediatric dentists: The study highlights the importance of collaborating with health professions outside of dentistry.Doctors and nurses are often the first health professionals to come into contact with children with special needs. They should therefore be made aware of the early signs of decay so that these patients can be referred for dental treatment timeously.Holistic management of children with special healthcare needs is essential to improve their overall well‐being. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Cheng et al papers. To view these articles, visit https://doi.org/10.1111/apt.17765 and https://doi.org/10.1111/apt.17807 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Cheng et al papers. To view these articles, visit https://doi.org/10.1111/apt.17765 and https://doi.org/10.1111/apt.17793 [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Majumdar et al paper. To view this article visit https://doi.org/10.1111/apt.13633. [ABSTRACT FROM AUTHOR]

Background: A short-term course of pegylated-interferon (Peg-IFN), or a long-term treatment with a third generation nucleot(s)ide analogue (NUC), of chronic hepatitis B (CHB) infection achieves viral suppression and may prevent disease progression. Owing to different mechanisms of action of the two regimens, a Peg-IFN and NUC combination treatment may be an attractive approach to enhance the off-treatment rates of virological and serological response., Aim: To review the literature on combinations of Peg-IFN plus NUC, including the simultaneous initiation of Peg-IFN and NUC in naïve patients; an 'add-on' combination, where Peg-IFN is started at variable times after the beginning of NUC; or a 'switch-to' strategy usually from NUC to Peg-IFN., Methods: We performed a PubMed literature search using the following terms individually or in combination: NUC, hepatitis B virus, chronic hepatitis, interferon, pegylated-interferon, nucleos(t)ide analogues, entecavir, tenofovir. English-language articles published up to December 2015, as well as conference proceedings from international meetings were reviewed. References from selected papers were reviewed and used if relevant., Results: While combination and NUC pre-treatment failed to increase HBsAg clearance rates, more promising results were achieved in patients under long-term effective NUC therapy., Conclusion: While Peg-IFN and nucleos(t)ide analogue combination therapy should not be recommended currently, the addition of or the switch to Peg-IFN in nucleos(t)ide analogue-treated patients with chronic hepatitis B infection may be useful option., (© 2016 John Wiley & Sons Ltd.)

LINKED CONTENT This article is linked to Mecci et al paper. To view this article, visit https://doi.org/10.1111/apt.15296. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In the light of the advances in HCV antiviral therapy, global control of HCV infection becomes feasible but depends on the capacity of countries to identify infected people and to offer them treatment. To achieve the WHO goal which targets a diagnosis rate of 90% by 2030, simplification of screening and diagnosis will be crucial. Methods: Published literature, unpublished data and expert consensus were used to determine key parameters, including point‐of‐care, rapid diagnostic testing, screening, the use of HCV core Ag and dried blood spots; starting from 2008 until November 2017. In addition, a manual search was undertaken to detect relevant papers or websites related to specific data from countries which underwent or are planning a programme of HCV elimination. Results: Several strategies have been developed and evaluated these last years to simplify and facilitate access to screening and diagnosis, the development of reliable HCV core antigen tests and new nucleic acid amplification technologies for use in decentralized settings. In high prevalence settings, a one‐step screening and diagnosis strategy could simplify diagnostic algorithms provided the cost is reduced. Finally, genotyping may no longer be required in the context of availability of pangenotypic antiviral therapy. Conclusions: Despite relevant advances in HCV screening and diagnosis, the overall diagnosis package is still too expensive today and efforts must be made to allow generalized implementation of reliable tests in low and middle income countries. These efforts will be key factors to foster a real public health approach to HCV elimination. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: UNAIDS 90‐90‐90 targets and Fast‐Track commitments are presented as precursors to ending the AIDS epidemic by 2030, through effecting a 90% reduction in new HIV infections and AIDS‐related deaths from 2010 levels (HIV epidemic control). Botswana, a low to middle‐income country with the third‐highest HIV prevalence, and Australia, a low‐prevalence high‐income country with an epidemic concentrated among men who have sex with men (MSM), have made significant strides towards achieving the UNAIDS 90‐90‐90 targets. These two countries provide lessons for different epidemic settings. This paper discusses the lessons that can be drawn from Botswana and Australia with respect to their success in HIV testing, treatment, viral suppression and other HIV prevention strategies for HIV epidemic control. Discussion: Botswana and Australia are on target to achieving the 90‐90‐90 targets for HIV epidemic control, made possible by comprehensive HIV testing and treatment programmes in the two countries. As of 2015, 70% of all people assumed to be living with HIV had viral suppression in Botswana and Australia. However, HIV incidence remains above one per cent in the general population in Botswana and in MSM in Australia. The two countries have demonstrated that rapid HIV testing that is accessible and targeted at key and vulnerable populations is required in order to continue identifying new HIV infections. All citizens living with HIV in both countries are eligible for antiretroviral therapy (ART) and viral load monitoring through government‐funded programmes. Notwithstanding their success in reducing HIV transmission to date, programmes in both countries must continue to be supported at current levels to maintain epidemic suppression. Scaled HIV testing, linkage to care, universal ART, monitoring patients on treatment over and above strengthened HIV prevention strategies (e.g. male circumcision and pre‐exposure prophylaxis) will all continue to require funding. Conclusions: The progress that Botswana and Australia have made towards meeting the 90‐90‐90 targets is commendable. However, in order to reduce HIV incidence significantly towards 2030, there is a need for sustained HIV testing, linkage to care and high treatment coverage. Botswana and Australia provide useful lessons for developing countries with generalized epidemics and high‐income countries with concentrated epidemics. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Maan et al, and Hussaini and Yoshida papers. To view these articles visit https://doi.org/10.1111/apt.14117 and https://doi.org/10.1111/apt.14161. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Liu et al and Liu and Kao papers. To view these articles, visit https://doi.org/10.1111/apt.15011 and https://doi.org/10.1111/apt.15329. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Degasperi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16685 and https://doi.org/10.1111/apt.16710 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Degasperi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16685 and https://doi.org/10.1111/apt.16696 [ABSTRACT FROM AUTHOR]

The current pandemic of coronavirus disease 2019 (COVID‐19) is recognized as a public health emergency of worldwide concern. Nanomaterials can be effectively used to detect, capture/inactivate or inhibit coronavirus cell entry/replication in the human host cell, preventing infection. Their potential for nanovaccines, immunoengineering, diagnosis, repurposing medication, and disinfectant surfaces targeting the novel coronavirus (SARS‐CoV‐2) is highlighted. In this systematic review the aim is to present an unbiased view of which and how nanomaterials can reduce the spread of COVID‐19. Herein, the focus is on SARS‐CoV‐2, analyzing 46 articles retrieved before December 31, 2020. The interface between nanomaterials is described, and the main mechanisms to inhibit SARS‐CoV‐2 pathogenesis and viral inactivation are also discussed. Nanocarbons, biopolymeric, copper, and silver nanoparticles are potential antiviral and virucidal agents toward self‐cleaning and reusable filter media and surfaces (e.g., facial masks), drug administration, vaccines, and immunodiagnostic assays. Trends in toxicology research and safety tests can help fill the main gaps in the literature and overcome health surveillance's challenges. Phytochemicals delivery by nanocarriers also stand out as candidates to target and bio‐friendly therapy. Nanocellulose might fill in the gaps. Future research using nanomaterials targeting novel therapies/prophylaxis measures to COVID‐19 and future outbreaks is discussed. [ABSTRACT FROM AUTHOR]

The particulate enzyme from Bacillus subtilis AHU 1031 catalyzed the synthesis of a polysaccharide and glycolipids from UDP — N-acetylmannosaminuronic acid (UDP-ManNAcUA), UDP — N-acetylglucosamine (UDP-GlcNAc), and UDP-glucose (UDP-Glc). The polysaccharide synthesis required UDP-ManNAcUA and UDP-GlcNAc, proceeded optimally at pH 8.5 and in the presence of 5 mM MgCl2 and 2.5 mM dithiothreitol, and was stimulated by the addition of UDP-Glc. The molar ratio of ManNAcUA, GlcNAc, and Glc incorporated into polysaccharide was calculated to be 1:1:1.8 from chemical analysis involving reduction with water soluble carbodiimide; its relative molecular mass was estimated to be 12000. The analysis of Smith degradation products revealed that the polysaccharide backbone is composed of repeating trisaccharide units comprising ManNAcUA, GlcNAc, and Glc. Based on the data regarding the time course of the incorporation of glucose into the polysaccharide, extra glucose seems to be attached to the polysaccharide backbone as lateral branches. The saccharide moieties of the glycolipids were identified as GlcNAc, ManNAcUA-GlcNAc, and Glc-ManNAcUA-GlcNAc from several analytical criteria. The addition of antibiotic 24010, a tunicamycin-like antibiotic, at 10 μg/ml resulted in almost complete inhibition of the synthesis of glycolipids and polysaccharide. It is therefore concluded that the glycolipids function as intermediates in polysaccharide formation. Incubation of the ManNAcUA-GlcNAc-linked lipid. (labeled in the ManNAcUA moiety) with the particulate enzyme and UDP-Glc resulted incorporation of radioactivity into a trisaccharide-linked lipid and a polysaccharide. These results suggest that the particulate enzyme utilizes the trisaccharide moiety of the Glc-ManNAcUA-GlcNAc-linked lipid for the elongation of the main polysaccharide chain presumed to be cell wall acidic polysaccharide of this strain. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Cacoub et al paper. To view this article, visit https://doi.org/10.1111/apt.15102. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Wong et al paper. To view this article, visit https://doi.org/10.1111/apt.14497. [ABSTRACT FROM AUTHOR]

Background: Over the past several years, hepatitis C therapy has been pegylated interferon and ribavirin based. Although protease inhibitor-based therapy has enhanced response rates in genotype 1, the recent advances in therapy have demonstrated a challenge in genotype 3, a highly prevalent infection globally., Aim: To provide a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies in genotype 3., Methods: A structured search in PubMed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers and abstracts in English., Results: HCV genotype 3 is more prevalent in Asia and among intra-venous drug users. Furthermore, it interferes with lipid and glucose metabolism, and the natural history involves a more rapid progression of liver disease and a higher incidence of hepatocellular carcinoma (HCC). New therapies with protease inhibitors have focused on genotype 1 largely and have demonstrated enhanced responses, but have limited activity against genotype 3. Thus far, in clinical trials, NS5B and NS5A inhibitors have performed more poorly in genotype 3, while a cyclophilin inhibitor, alisporivir, has shown promise., Conclusions: As treatments for HCV have evolved, genotype 3 has become the most difficult to treat. Furthermore, genotype 3 has special characteristics, such as insulin resistance and alterations in lipid metabolism, which may partly explain the lower treatment responses. A great deal of emphasis on advancing therapy is needed in this population that appears to have a more rapid progression of liver disease and a higher incidence of HCC.

This review focuses on the important contributions that macromolecular crystallography has made over the past 12 years to elucidating structures and mechanisms of the essential proteases of coronaviruses, the main protease (Mpro) and the papain-like protease (PLpro). The role of X-ray crystallography in structure-assisted drug discovery against these targets is discussed. Aspects dealt with in this review include the emergence of the SARS coronavirus in 2002-2003 and of the MERS coronavirus 10 years later and the origins of these viruses. The crystal structure of the free SARS coronavirus Mpro and its dependence on pH is discussed, as are efforts to design inhibitors on the basis of these structures. The mechanism of maturation of the enzyme from the viral polyprotein is still a matter of debate. The crystal structure of the SARS coronavirus PLpro and its complex with ubiquitin is also discussed, as is its orthologue from MERS coronavirus. Efforts at predictive structure-based inhibitor development for bat coronavirus Mpros to increase the preparedness against zoonotic transmission to man are described as well. The paper closes with a brief discussion of structure-based discovery of antivirals in an academic setting. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Chon et al paper. To view this article, visit https://doi.org/10.1111/apt.16267 [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causal agent for coronavirus disease 2019 (COVID‐19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS‐CoV‐2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS‐CoV‐2 for infection. Preincubation of SARS‐CoV‐2 with a neutralizing antibody specific to ApoE led to inhibition of SARS‐CoV‐2 infection. The ApoE neutralizing antibody efficiently blocked SARS‐CoV‐2 infection of human iPSC‐derived astrocytes and air–liquid interface organoid models in addition to human ACE2‐expressing HEK293T cells and Calu‐3 lung cells. ApoE mediates SARS‐CoV‐2 entry through binding to its cellular receptors such as the low density lipoprotein receptor (LDLR). LDLR knockout or ApoE mutations at the receptor binding domain or an ApoE mimetic peptide reduced SARS‐CoV‐2 infection. Furthermore, we detected strong membrane LDLR expression on SARS‐CoV‐2 Spike‐positive cells in human lung tissues, whereas no or low ACE2 expression was detected. This study provides a new paradigm for SARS‐CoV‐2 cellular entry through binding of ApoE on the lipoviral particles to host cell receptor(s). Moreover, this study suggests that ApoE neutralizing antibodies are promising antiviral therapies for COVID‐19 by blocking entry of both parental virus and variants of concern. [ABSTRACT FROM AUTHOR]

The spike protein of SARS‐CoV‐2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS‐CoV‐2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike‐focused vaccines and therapeutics. Compared with the fast‐evolving spike protein, targeting host ACE2 offers an alternative antiviral strategy that is more resistant to viral evolution and can even provide broad prevention against SARS‐CoV and HCoV‐NL63. Here, we use prime editor (PE) to precisely edit ACE2 at structurally selected sites. We demonstrated that residue changes at Q24/D30/K31 and/or K353 of ACE2 could completely ablate the binding of tested viruses while maintaining its physiological role in host angiotensin II conversion. PE‐mediated ACE2 editing at these sites suppressed the entry of pseudotyped SARS‐CoV‐2 major variants of concern and even SARS‐CoV or HCoV‐NL63. Moreover, it significantly inhibited the replication of the Delta variant live virus. Our work investigated the unexplored application potential of prime editing in high‐risk infectious disease control and demonstrated that such gene editing‐based host factor reshaping strategy can provide broad‐spectrum antiviral activity and a high barrier to viral escape or resistance. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Starbuck et al (2012) Are we prepared to help low-resource communities cope with a severe influenza pandemic? Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12040. Recent research involving lab-modified H5N1 influenza viruses with increased transmissibility and the ongoing evolution of the virus in nature should remind us of the continuing importance of preparedness for a severe influenza pandemic. Current vaccine technology and antiviral supply remain inadequate, and in a severe pandemic, most low-resource communities will fail to receive adequate medical supplies. However, with suitable guidance, these communities can take appropriate actions without substantial outside resources to reduce influenza transmission and care for the ill. Such guidance should be completed, and support provided to developing countries to adapt it for their settings and prepare for implementation. [ABSTRACT FROM AUTHOR]

Please cite this paper as: He et al. (2013) Amaryllidaceae alkaloids inhibit nuclear-to-cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Influenza and Other Respiratory Viruses 7(6), 922-931. Background Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents. Objective To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178). Methods Antiviral activities of the compounds were tested in time-of-addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1-HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively. Results Among the alkaloids, lycorine ( AA1), hippeastrine ( AA2), hemanthamine ( AA3) and 11-hydroxy vittatine ( AA4) exhibited antiviral activities, with EC90 values of 0·52, 82·07, 4·15, and 13·45 μ m, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single-round and multi-round of replication. Conclusion Four Amaryllidaceae alkaloids were first determined that could exert anti-influenza activities after virus entry into cells. Furthermore, AA1 and AA3 could inhibit nuclear-to-cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti-influenza drug candidates. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kennedy et al. for the 2009 Pandemic H1N1 Influenza-Associated Lower Respiratory Tract Hemorrhage Working Group. (2012) Lower respiratory tract hemorrhage associated with 2009 pandemic influenza A (H1N1) virus infection. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12022. Background Influenza-associated lower respiratory tract hemorrhage (LRTH) has been reported in previous pandemics and is a rare complication of seasonal influenza virus infection. We describe patients with LRTH associated with 2009 pandemic influenza A (H1N1) (pH1N1) virus infection identified from April 2009 to April 2010 in the United States. Methods We ascertained patients with pH1N1-associated LRTH through state and local surveillance, the Emerging Infections Program, and CDCs Infectious Diseases Pathology Branch. All patients had influenza A, evidence of pneumonia, and evidence of LRTH. Results We identified 44 cases; the median number of days from illness onset to clinical signs of LRTH was one. Hemoptysis or respiratory tract bleeding was documented in 40% of pH1N1-associated LRTH cases, often present early during the course of illness. Twenty-one (48%) patients with LRTH had no other hemorrhagic diatheses. Seven (23%) patients with LRTH received antiviral treatment within two days of illness onset. Conclusions During influenza season, clinicians should consider influenza infection in the differential diagnosis for patients presenting with hemoptysis or other signs or symptoms of LRTH. While the impact of timing of antiviral therapy on this complication has not been studied, the rapid progression of LRTH may support use of early empiric therapy. Continued investigation is necessary to betterdefine the clinical spectrum of both seasonal influenza- and pH1N1-associated LRTH. [ABSTRACT FROM AUTHOR]

Linked Content This article should be linked to Londoño et al and Huang et al papers. To view these articles visit https://doi.org/10.1111/apt.13985 and https://doi.org/10.1111/apt.14080. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Rossotti et al and Schwabl et al papers. To view these articles visit https://doi.org/10.1111/apt.13982 and https://doi.org/10.1111/apt.13844. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Schwabl et al papers. To view these articles visit https://doi.org/10.1111/apt.13844 and https://doi.org/10.1111/apt.13903. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al papers. To view these articles visit https://doi.org/10.1111/apt.13774 and https://doi.org/10.1111/apt.13859. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al and Zhang et al papers. To view these articles visit https://doi.org/10.1111/apt.13774 and https://doi.org/10.1111/apt.13814. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al, and Wei and Wang papers. To view these articles visit https://doi.org/10.1111/apt.13774 and https://doi.org/10.1111/apt.13829. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Roberts et al. (2012) Overview of the conference. Influenza and Other Respiratory Viruses 7(Suppl. 1), 2-6. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Ison. (2012) Clinical use of approved influenza antivirals: therapy and prophylaxis. Influenza and Other Respiratory Viruses 7(Suppl. 1), 7-13. Currently, there are two commonly used classes of antiviral agents approved for the prevention of and treatment for influenza: the M2 Inhibitors (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir, laninamivir, peramivir and zanamivir). These agents have been proven to be safe and effective alone or in combination for the treatment of uncomplicated influenza in otherwise healthy individuals. Although there are few prospective, randomized studies of these antivirals for the treatment of pregnant women, hospitalized patients, and immunocompromised patients infected with seasonal, pandemic, or avian H5N1 influenza, these agents are widely used for these indications. This article reviews the pharmacokinetics and clinical data available relative to the use of commercially available antiviral agents for the prevention of and treatment for influenza. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Okomo-Adhiambo et al. (2012) Assays for monitoring susceptibility of influenza viruses to neuraminidase inhibitors. Influenza and Other Respiratory Viruses 7(Suppl. 1), 44-49. Close monitoring of drug susceptibility among human influenza viruses was necessitated by widespread resistance to M2 inhibitors in influenza H1N1 (pre-pandemic and 2009 pandemic) and H3N2 viruses, and of oseltamivir resistance in pre-pandemic H1N1 viruses. The FDA-approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir, as well as investigational NAIs, peramivir and laninamivir, are currently the principal treatment options for managing influenza infection. However, there are challenges associated with assessing virus susceptibility to this class of drugs. Traditional cell culture-based assays are not reliable for phenotypic testing of NAI susceptibility due to complexity in interpretation. Two types of laboratory assays are currently available for monitoring NAI susceptibility, phenotypic such as the neuraminidase inhibition (NI) assay and genotypic. The NI assay's requirement for propagated virus lengthens testing turnaround; therefore, the need for timely detection of molecular markers associated with NAI resistance (e.g., H275Y in H1N1) has spurred the development of rapid, high-throughput assays, such as real-time RT-PCR and pyrosequencing. The high sensitivity of genotypic assays allows testing of clinical specimens thus eliminating the need for virus propagation in cell culture. The NI assays are especially valuable when a novel virus emerges or a new NAI becomes available. Modifications continue to be introduced into NI assays, including optimization and data analysis criteria. The optimal assay of choice for monitoring influenza drug susceptibility varies widely depending on the needs of laboratories (e.g., surveillance purposes, clinical settings). Optimally, it is desirable to combine functional and genetic analyses of virus isolates and, when possible, the respective clinical specimens. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Zambon. (2012) Surveillance for antiviral resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 37-43. In the 10 years since licensure of neuraminidase inhibitor drugs, their use has steadily increased, especially during the pandemic of 2009. Experience now indicates that factors which influence the emergence of high level resistance include the nature of drug binding to target, viral subtype, the use of post exposure prophylaxis and a lack of immunity in the host as seen in children and immunocompromised individuals. These factors point towards targetted surveillance programmes for the early identification of transmissible drug resistance. [ABSTRACT FROM AUTHOR]

Please cite this paper as: McKimm-Breschkin (2012) Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 25-36. There are two major classes of antivirals available for the treatment and prevention of influenza, the M2 inhibitors and the neuraminidase inhibitors (NAIs). The M2 inhibitors are cheap, but they are only effective against influenza A viruses, and resistance arises rapidly. The current influenza A H3N2 and pandemic A(H1N1)pdm09 viruses are already resistant to the M2 inhibitors as are many H5N1 viruses. There are four NAIs licensed in some parts of the world, zanamivir, oseltamivir, peramivir, and a long-acting NAI, laninamivir. This review focuses on resistance to the NAIs. Because of differences in their chemistry and subtle differences in NA structures, resistance can be both NAI- and subtype specific. This results in different drug resistance profiles, for example, the H274Y mutation confers resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 NAs. Mutations at E119, D198, I222, R292, and N294 can also reduce NAI sensitivity. In the winter of 2007-2008, an oseltamivir-resistant seasonal influenza A(H1N1) strain with an H274Y mutation emerged in the northern hemisphere and spread rapidly around the world. In contrast to earlier evidence of such resistant viruses being unfit, this mutant virus remained fully transmissible and pathogenic and became the major seasonal A(H1N1) virus globally within a year. This resistant A(H1N1) virus was displaced by the sensitive A(H1N1)pdm09 virus. Approximately 0·5-1·0% of community A(H1N1)pdm09 isolates are currently resistant to oseltamivir. It is now apparent that variation in non-active site amino acids can affect the fitness of the enzyme and compensate for mutations that confer high-level oseltamivir resistance resulting in minimal impact on enzyme function. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Regan et al. (2012) Epidemiology of influenza A (H1N1)pdm09-associated deaths in the United States, September-October 2009. Influenza and Other Respiratory Viruses 6(601), e169-e177. Background From April to July 2009, the United States experienced a wave of influenza A (H1N1)pdm09 virus (H1N1pdm09) infection. The majority of the deaths during that period occurred in persons <65 years of age with underlying medical conditions. Objective To describe the epidemiology of H1N1pdm09-associated deaths in the US during the fall of 2009. Methods We collected demographic, medical history, and cause of death information on a nationally representative, stratified random sample of 323 H1N1pdm09-associated deaths that occurred during September 1-October 31, 2009. Results Data were available for 302/323 (93%) deaths. Most cases (74%) were 18-64 years of age and had ≥1 underlying medical condition (72%). Among cases aged <18 years, 16/43 (37%) had a chronic lung disease, and 15/43 (35%) a neurological disorder; among cases aged ≥18 years, 94/254 (37%) had a chronic lung disease and 84/254 (33%) had a metabolic disorder. The median number of days between symptom onset and death was six among children (range, 1-48) and 12 among adults (range, 0-109). Influenza antiviral agents were prescribed for 187/268 (70%) of cases, but only 48/153 (31%) received treatment within 2 days of illness onset. Conclusions The characteristics of H1N1pdm09 deaths identified during the fall of 2009 were similar to those occurring April-July 2009. While most cases had conditions that were known to increase the risk for severe outcomes and were recommended to receive antiviral therapy, a minority of cases received antivirals early in the course of illness. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Bramley et al. Intensive care unit patients with 2009 pandemic influenza A (H1N1pdm09) virus infection - United States, 2009. Influenza and Other Respiratory Viruses 6(601), e134-e142. Background The influenza A (H1N1pdm09) [pH1N1] virus resulted in intensive care unit (ICU) admissions, acute respiratory distress syndrome (ARDS), and death. Objectives To describe the characteristics of ICU patients with pH1N1 virus infection in the United States during the spring and fall of 2009 and to describe the factors associated with severe complications including ARDS and death. Patients/Methods Through two national case-series conducted during spring and fall of 2009, medical charts were reviewed on ICU patients with laboratory-confirmed pH1N1 infection by real-time reverse-transcriptase polymerase chain reaction. Results The majority (77%) of 154 patients hospitalized in an ICU were <50 years of age, and 65% had at least one underlying medical condition. One hundred and twenty-eight (83%) patients received influenza antiviral agents; 29% received treatment ≤2 days after illness onset. Forty-eight (38%) patients developed ARDS and 37 (24%) died. Patients with ARDS were more likely to be morbidly obese (36% versus 19%, P = 0·04) and patients who died were less likely to have asthma (11% versus 28%, P = 0.05). Compared with patients who received treatment ≥6 days after illness onset, patients treated ≤2 days after illness onset were less likely to develop ARDS (17% versus 37%, P < 0.01) or die (7% versus 35%, P < 0·01). Conclusions Among patients hospitalized in an ICU with pH1N1 virus infection, ARDS was a common complication, and one-quarter of patients died. Patients with asthma had less severe outcomes. Early treatment with influenza antiviral agents was likely beneficial, especially when initiated ≤2 days after illness onset. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Borders-Hemphill and Mosholder (2012) U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic. Influenza and Other Respiratory Viruses 6(601), e129-e133. Background The 2009 H1N1 influenza pandemic in the United States occurred from April 2009 to April 2010. The 2009 H1N1 influenza virus was susceptible to neuraminidase inhibitors (oseltamivir and zanamivir). Objectives To characterize the 2009 H1N1 influenza pandemic in the United States from April 2009 to April 2010 using weekly influenza antiviral prescription utilization data and the CDC's weekly reports of the number of visits for influenza-like-illnesses by the Influenza Sentinel Provider Surveillance Network. Methods A proprietary outpatient data source used by the FDA, which captures adjudicated U.S. prescription claims for select influenza antiviral drugs, was used to conduct this analysis. Data were extracted weekly and analyzed for surveillance during the pandemic. Results were compiled at the end of the pandemic. Results Oseltamivir has dominated the U.S. influenza antiviral market share of dispensed prescriptions since approval in October 1999 and was the primary influenza antiviral drug used during the 2009 H1N1 influenza pandemic. However, commercial availability of the suspension formulation of oseltamivir was reduced by high demand during the pandemic. Dispensed prescription trends of other influenza antiviral medications studied followed that those of oseltamivir, even antivirals for which the 2009 H1N1 strains showed resistance. Conclusion Weekly prescription utilization of all influenza antivirals used to treat influenza during the seasonal influenza outbreak followed the same trend of weekly reports of the number of visits for influenza-like-illnesses (ILI) by the Influenza Sentinel Provider Surveillance Network. The ILI epidemic curve resembled dispensed antiviral prescription trends (both overall and stratified by age), providing some corroboration for the surveillance data. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Karlsson et al. (2012) Review on the impact of pregnancy and obesity on influenza virus infection. Influenza and Other Respiratory Viruses 6(6), 449-460. A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Dharan et al. (2011) Clinical and virologic outcomes in patients with oseltamivir-resistant seasonal influenza A (H1N1) infections: results from a clinical trial. Influenza and Other Respiratory Viruses 6(3), 153-158. Nineteen patients with oseltamivir-resistant seasonal influenza A (H1N1) infections were randomized to receive oseltamivir or placebo. Nasopharyngeal swabs were obtained, and clinical and virologic outcomes were compared, stratified by early or late treatment. Neuraminidase inhibition assay and pyrosequencing for H275Y confirmed resistance. Twelve (63%) patients received oseltamivir; 8 (67%) received late treatment. Seven (37%) patients received placebo; 6 (86%) presented >48 hours after onset. Time to 50% decrease in symptom severity, complete symptom resolution, and first negative culture were shortest among the early treatment group. While sample size prohibits a strong conclusion, future studies should evaluate for similar trends. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Coleman et al. (2011) Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season. Influenza and Other Respiratory Viruses 5(6), 404-408. Background Data regarding both rates of acute respiratory illness in health care workers and experience with long-term antiviral prophylaxis are sparse. Objective To determine the efficacy and tolerability of oseltamivir prophylaxis versus seasonal influenza vaccine for the prevention of influenza among health care workers. Methods We conducted a pilot, randomized control study during the 2007/2008 influenza season in a tertiary care setting. Adult health care workers 18-69 years of age were recruited and randomly assigned in a 4:1 ratio to receive either oseltamivir (Tamiflu®; Roche) 75 mg once daily prophylaxis or seasonal influenza (Fluviral®) vaccine. Results Of 56 adults enrolled, 12 received vaccine and 44 received prophylaxis. Incidence of symptomatic laboratory-confirmed influenza was similar for participants in the vaccine and prophylaxis arms (17% and 24%, respectively; P = 0·71). Participants who developed an acute respiratory illness during the study period reported working 85% of scheduled work days, and 29% stated that they worked despite feeling miserable because they were too busy to stay home. Of 42 participants who initiated oseltamivir prophylaxis, four discontinued it owing to side effects. Median duration of oseltamivir prophylaxis was 121 days, with 34 (81%) continuing ≥12 weeks. Conclusions During an extended season of suboptimal vaccine match, 22% of health care workers receiving antiviral prophylaxis or seasonal influenza vaccine developed symptomatic laboratory-confirmed influenza. Long-term antiviral prophylaxis against influenza was generally well tolerated with good compliance. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Neumann G, Kawaoka Y. (2011) The first influenza pandemic of the new millennium. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00202.x. In the spring of 2009, a novel influenza A virus of the H1N1 subtype emerged that transmitted efficiently among humans; by June of 2009, the outbreak reached pandemic status. The pandemic virus possesses six viral RNA segments from so-called triple reassortant swine viruses that emerged in North American pig populations in the late 1990s and two viral RNA segments from Eurasian avian-like swine influenza viruses. Most human infections with the virus have been mild; however, severe and fatal infections occurred among certain risk groups, but also among those without any known risk factors. Here, we summarize the evolutionary, epidemiological, clinical, and molecular findings on the pandemic virus. We also discuss the arsenal of antiviral compounds and vaccines available to prevent and treat infections with the virus. [ABSTRACT FROM AUTHOR]