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Silver nanoparticles have shown inhibitory capabilities and its use in battling viral infections are strengthened by its potent antibacterial activity. Notably, since it directly affects antiviral efficacy, the proper choice of synthesis process for making silver nanoparticles is a vital element to be taken into consideration. The synthesis of silver nanoparticles for the treatment of viral and bacterial infections involves creating silver particles at the nanoscale with unique antimicrobial properties. Various methods exist for synthesizing silver nanoparticles, including chemical reduction, green synthesis, and physical methods. Chemical reduction involves using reducing agents to convert silver ions into silver nanoparticles. Green synthesis employs reducing agents in an environmentally friendly manner. Physical methods rely on techniques such as laser ablation or thermal evaporation to produce silver nanoparticles. In order to provide technological guidance for choosing antiviral silver nanoparticle manufacturing methods, this paper introduces and explores alternative synthesis methods for creating silver nanoparticles. [ABSTRACT FROM AUTHOR]

Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV- associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan-Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of>01× 109 CD4 cells/I and/or at least one viral load <500 copies/mI during the first 2 years following diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and 2002 were included in the study. In the Cox model, the only factors independently associated with OS were HAART response [relative hazard (RH) 019; 95% confidence interval (CI) 0.06-060], complete remission (RH 0.30, 95% CI 0.13-0.72), and age ≤45 years (RH 0.23; 95% CI 0.09-0.60). Median survival time in patients without HAART response was 186 months, whereas the median survival time in patients with HAART response was not reached (89% OS at 24 months). In this cohort, a significant improvement in survival was found in patients with HIV-HD who responded to HAART. [ABSTRACT FROM AUTHOR]

Recent clinical studies demonstrated the achievement of lymphoma responses in patients with Hepatitis C virus‐associated indolent lymphoproliferative disorders (LPD) receiving direct‐acting antivirals (DAAs) as their sole treatment. However, the molecular mechanisms underlying LPD responses to DAAs are still poorly understood. In their paper the authors provide new molecular insights on this issue, reporting intraclonal diversification and persistence of B‐cell clones in most cases, despite viral eradication and beneficial clinical outcome. These provocative data suggest that the achievement of molecular response is probably not required for a 'functional cure' of these patients. Further comprehensive immunogenetic and mutational studies would be fundamental to dissect this biological puzzle and, ultimately, to refine improved treatment strategies in this setting. Commentary on: Mazzaro et al. Persistence of monoclonal B‐cell expansion and intraclonal diversification despite virus eradication in patients affected by hepatitis C virus‐associated lymphoproliferative disorders. Br J Haematol 2023;203:237‐243. [ABSTRACT FROM AUTHOR]

Modern health‐care systems have customarily approached hepatitis C in ways that resemble the public health approach to HIV/AIDS known as 'HIV exceptionalism'. HIV exceptionalism describes the unusual emphasis on privacy, confidentiality and consent in approaches to HIV and was partly developed to address HIV/AIDS‐related stigma. In the case of hepatitis C, exceptionalist approaches have included diagnosis and treatment by specialist physicians and other 'boutique' public health strategies. The recent availability of highly effective, direct‐acting antivirals alongside goals to eliminate hepatitis C have heralded dramatic changes to hepatitis C health care, including calls for its 'normalisation'. The corollary to exceptionalism, normalisation aims to bring hepatitis C into routine, mainstream health care. This article draws on interviews with stakeholders (n = 30) who work with hepatitis C‐affected communities in policy, community, legal and advocacy settings in Australia, alongside Fraser et al.'s (2017, International Journal of Drug Policy, 44, 192–201) theorisation of stigma, and Rosenbrock et al.'s (1999, The AIDS policy cycle in Western Europe: from exceptionalism to normalisation. WZB Discussion Paper, No. P 99‐202) critique of normalisation to consider the perceived effects of hepatitis C normalisation. Stakeholders described normalisation as a stigma‐reducing process. However, they also expressed concerns about the ongoing stigma and discrimination that is not ameliorated by normalisation. We suggest that in centring normalisation, changes in health care may exaggerate the power of technological solutions to transform the meanings of hepatitis C. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a numerical and analytical study of the HIV‐1 infection of CD4+ T‐cells conformable fractional mathematical model. This model is studied analytically by Kudryashov and modified Kudryashov methods and numerically by finite difference method. A comparison between the results of the analytical and numerical methods is investigated. We also give some figures that show how accurate the solutions will be obtained from analytical and numerical methods. [ABSTRACT FROM AUTHOR]

Per the well‐known resistance of hepatitis B virus to nucleoside/nucleotide analogs, alternative treatment options with higher resistance barriers have been approved for use in both treatment‐naïve and lamivudine‐resistant hepatitis B virus infections. This phase I study was conducted in adults with normal and impaired renal function to evaluate the effect of renal impairment on the pharmacokinetics of besifovir, a prodrug of an acyclic nucleotide phosphonate, that is mainly cleared via renal excretion. An open‐label, single‐dose parallel‐group clinical study was conducted in subjects with normal renal function and mild, moderate, and severe renal impairment. Subjects received a single oral dose of besifovir dipivoxil 150 mg, and serial blood and urine samples were collected for up to 72 hours after dosing to assess the pharmacokinetic characteristics of besifovir. The extent of plasma exposure of besifovir, detected as its major and active metabolites, LB80331 and LB80317, respectively, increased with worsening renal function. Compared to the subjects with normal renal function, the mean areas under the concentration‐time curves of LB80331 increased by 1.5‐, 2.5‐, and 4.5‐fold in subjects with mild, moderate, and severe impairment, respectively. LB80317 showed a 1.8‐, 3.2‐, and 6.2‐fold increase in subjects with mild, moderate, and severe renal impairment compared to those with normal function. The ratios of LB80331 renal clearance and the average estimated glomerular filtration rate of each renal impairment group with respect to the normal group were similar. The increase in plasma exposure and decrease in renal clearance suggest the need to adjust dosage regimens in patients with moderate to severe renal impairment. [ABSTRACT FROM AUTHOR]

A series of 42 diarylethers and their analogues were synthesized. All compounds were tested in vitro against six viruses. Two diarylethers in this series demonstrated selective and remarkable activity toward Human Coronavirus OC43 and Human Adenovirus 5 (SI 97.4 and 99.7, respectively). QSARs for the investigated antiviral activities were explored. The analysis was based on a large library of 113 diarylethers and their analogues comprising the compounds reported in this paper, as well as compounds previously synthesized and tested by us. Statistically reliable regression and discriminant models were derived which revealed structural and physicochemical features of the compounds important for the antiviral activities. These models may be used as guidance for synthesis of lead compounds with promising antiviral activity toward the investigated viruses. [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]

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.

The entire world is struggling to control the spread of coronavirus (COVID‐19) as there are no proper drugs for treating the disease. Under clinical trials, some of the repurposed antiviral drugs have been applied to COVID‐19 patients and reported the efficacy of the drugs with the diverse inferences. Molecular topology has been developed in recent years as an influential approach for drug design and discovery in which molecules that are structurally related show similar pharmacological properties. It permits a purely mathematical description of the molecular structure so that in the development of identification of new drugs can be found through adequate topological indices. In this paper, we study the structural properties of the several antiviral drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, remdesivir, theaflavin, nafamostat, camostat, umifenovir and bevacizumab by considering the distance and bond measures of chemical compounds. Our quantitative values of the topological indices are extremely useful in the recent development of designing new drugs for COVID‐19. [ABSTRACT FROM AUTHOR]

Little has been published in terms of dose-finding methodology in virology. Aside from a few papers focusing on HIV, the considerable progress in dose-finding methodology of the last 25 years has focused almost entirely on oncology. While adverse reactions to cytotoxic drugs may be life threatening, for anti-viral agents we anticipate something different: side effects that provoke the cessation of treatment. This would correspond to treatment failure. On the other hand, success would not be yes/no but would correspond to a range of responses, from small, no more than say 20% reduction in viral load to the complete elimination of the virus. Less than total success matters since this may allow the patient to achieve immune-mediated clearance. The motivation for this article is an upcoming dose-finding trial in chronic norovirus infection. We propose a novel methodology whose goal is twofold: first, to identify the dose that provides the most favorable distribution of treatment outcomes, and, second, to do this in a way that maximizes the treatment benefit for the patients included in the study. [ABSTRACT FROM AUTHOR]

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."

Wuhan, a city of China, is the epicenter for the pandemic outbreak of coronavirus disease‐2019 (COVID‐19). It has become a severe public health challenge to the world and established a public health emergency of international worry. This infectious disease has pulled down the economy of almost all top developed nations. The coronaviruses (CoVs) known for various epidemics caused time to time. Infectious diseases such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), followed by COVID‐19, are all coronaviruses led outbreaks that scourged the history of mankind. CoVs evolved themselves to more infectious, transmissible, and more pandemic with time. To prevent the spread of the SARS‐CoV‐2, many countries have ordered the complete lockdown to combat the outbreak. This paper briefly discussed the historical background of CoVs and the evolution of human coronaviruses (HCoVs), the case studies and the development of their antiviral medications. The viral infection encountered with present‐day challenges and futuristic approaches with the help of nanotechnology to minimize the spread of infectious viruses. The antiviral drugs and their clinical advances, along with herbal medicines for viral inhibition and immunity boosters, are described. Elaboration of tables related to CoVs for the compilation of the literature has been adopted for the better understanding. [ABSTRACT FROM AUTHOR]

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]

Summary: Hepatitis C virus contributes to substantial and growing mortality and morbidity. Fortunately, the advent of highly effective interferon‐free direct‐acting antiviral (DAA) medications and new diagnostic tests has the potential to dramatically alter the epidemiologic trajectory of hepatitis C, particularly for "hard‐to‐reach" populations. Treatment advances and cure will also likely alter the individual experience of living with hepatitis C. However, it is not yet known in what capacity. This paper provides an overview of the population‐level impact of DAA treatment, highlighting the need to further our understanding of the impact of treatment on behaviour, health and wellbeing through lived experience and more sensitive patient‐reported outcome measures. [ABSTRACT FROM AUTHOR]

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]

Abstract: Around 71 million people are chronically infected with HCV worldwide. HCV antiviral drug development has been remarkable. The availability of pangenotypic direct‐acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN‐free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8‐12 weeks of treatment. Programmes to eliminate HCV must include increased screening (risk‐based and universal), linkage to care, as well as increased access to treatment worldwide. In this paper, we will review the available data on recently approved direct‐acting antiviral agents, with sustained virological response that reaches almost 100%. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection, a major cause of end-stage liver disease, is a common comorbidity in patients on dialysis and causes increased morbidity and mortality. Historically HCV has been extremely difficult to cure with interferon and ribavirin-based therapies, which are also associated with significant side effects, and few dialysis patients ever received HCV treatment. However, in the last 4 years, interferon-free direct-acting antiviral therapies have been approved, and several combinations have been studied in dialysis patients. A recently approved, pan-genotypic, direct-acting antiviral regimen, glecaprevir and pibrentasvir, may simplify prescribing. The simplicity of these new therapies, with few side effects, makes it possible for nephrologists to treat HCV infection in their patients on dialysis. We review the workflow and motivation behind nephrology-led management of HCV infection. We highlight the importance of identifying which patients need referral to a hepatologist or HCV specialist prior to treatment and which can be managed by their nephrologist. Nephrologist involvement would lead to improved access to treatment and ensure that appropriate patients are referred for HCV treatment. In this paper, we review the background of HCV infection, its effect on dialysis patients, and impact on kidney transplantation. In addition, we outline the therapy options for each genotype of HCV, and we discuss the benefits and barriers to nephrology-led HCV treatment. [ABSTRACT FROM AUTHOR]

This review paper summarizes the epidemiology of hepatitis C virus (HCV) and chronic HCV infection, including HCV virology and treatment regimens. Specifically, we focus on the evolution of past, current, and future HCV treatment options, the reasons for treatment failure, and the impact of resistance-associated variants on treatment success. [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]

In this paper, a series of N-(4-substituted phenyl) acetamide derivatives bearing 1,3,4-oxadiazole moiety were synthesised. Preliminary bioassays revealed that these compounds not only exhibited favourable antiviral activities toward tobacco mosaic virus (TMV) but also demonstrated sustained inhibition activities against plant pathogenic bacteria, including Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri. Among the derivatives, TC8 and TC20 exerted the strongest curative activities against TMV, with half-maximal effective concentration (EC50) values of 239.5 and 236.2 µg/mL, respectively, which were comparable to that of ningnanmycin (EC50=273.2 µg/mL). Given their simple synthesis, the target compounds can serve as alternative antiviral candidates. [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]

Aims Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. Methods Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990–present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. Results Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53–96%) and in patients enrolled in methadone maintenance programs (67–96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28–94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72–100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. Conclusion High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them. [ABSTRACT FROM AUTHOR]

The article presents abstracts of several studies on hepatology. "Antifibrotic Action of Interferon Gamma Treatment in Patients With Chronic Hepatitis B Virus Infection," "A Noninvasive Model for Assessment of Liver Fibrosis of Liver Fibrosis in Chronic Hepatitis B," "Regulation of Constitutive Endocytosis by Dynamin and Cortactin Phosphorylation," and "Granulin-Epithelin Precursor and p53 in Hepatocellular Carcinoma."

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 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]

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]

Shared parameter joint models provide a framework under which a longitudinal response and a time to event can be modelled simultaneously. A common assumption in shared parameter joint models has been to assume that the longitudinal response is normally distributed. In this paper, we instead propose a joint model that incorporates a two-part 'hurdle' model for the longitudinal response, motivated in part by longitudinal response data that is subject to a detection limit. The first part of the hurdle model estimates the probability that the longitudinal response is observed above the detection limit, whilst the second part of the hurdle model estimates the mean of the response conditional on having exceeded the detection limit. The time-to-event outcome is modelled using a parametric proportional hazards model, assuming a Weibull baseline hazard. We propose a novel association structure whereby the current hazard of the event is assumed to be associated with the current combined (expected) outcome from the two parts of the hurdle model. We estimate our joint model under a Bayesian framework and provide code for fitting the model using the Bayesian software Stan. We use our model to estimate the association between HIV RNA viral load, which is subject to a lower detection limit, and the hazard of stopping or modifying treatment in patients with HIV initiating antiretroviral therapy. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The therapeutic landscape for the treatment of chronic hepatitis C virus infection has been rapidly evolving, and by 2016 there will be six approved, all-oral regimens for use in patients in the USA and most of Western Europe. However, as many as patient populations will have limited access to new direct acting antiviral regimens, patients and physicians are often faced with the challenge of selecting the best regimen available, as opposed to the optimal treatment. In this paper, the challenges and opportunities in developing a high cure regimen for different patient populations will be discussed and highlighted through case-based scenarios. [ABSTRACT FROM AUTHOR]

This paper aims to review the rôle of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases. There is a clearly defined and substantial rôle for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area. This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area. The recent discovery of the transcription factor nuclear factor κB (NF-κB) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-κB, are discussed. Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-α, IL-1, IL-6, IL-8 and β-interferon. The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-κB antagonists may offer important therapeutic benefits. [ABSTRACT FROM AUTHOR]

The entry of new all-oral direct acting antiviral therapy for hepatitis C provides an opportunity to scale up HCV care in low- and middle-income countries. In HIV, use of dried blood spots (DBS) has facilitated the diagnosis and management of HIV in resource-poor settings. DBS may be used in a similar way to facilitate diagnosis and management of HCV. Here, we present a systematic review of the literature of DBS for HCV RNA detection and genotyping. Using an a priori review protocol, three databases were searched for studies published up to August 2013 that reported the use of dried blood and serum spots in genotyping, detection and measurement of HCV RNA, as well as the rate of degradation of HCV RNA when stored in DBS at room temperature. Nine papers were eligible for inclusion; eight studied DBS and one dried serum . Two studies measured concordance between genotype and subtype determined by DBS and whole plasma and both found 100% concordance. Four studies measured endpoint detection limits of HCV RNA-positive samples by DBS and found positive predictive values of 100% down to 250, 334, 2500 and 24160 IU/ mL. Two studies found deterioration of HCV RNA in DBS samples stored at room temperature, while two others failed to detect such deterioration. These results support the potential use of DBS for genotyping and HCV RNA detection. Studies of the use of DBS for HCV RNA viral load measurement and of the rate of degradation of HCV RNA when stored in DBS at ambient temperatures remain inconclusive. [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]

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]

This paper describes the stereoselective synthesis of a series of functionalized cyclobutane and cyclobutene L-nucleoside analogues featuring a methylene spacer between the carbocycle and the nucleobase. These L-nucleoside analogues were subjected to comprehensive screening for antiviral activity. To obtain knowledge at the molecular structural level relevant for designing future analogues, the mechanism of action of these L-nucleoside analogues as anti-herpes simplex virus agents was investigated by computational approaches. In particular, protein-ligand docking calculations were used to rationalize the ability of the prodrug candidates to be activated. Docking experiments were performed on the three kinases involved in the activation process of thymine and guanine derivatives. [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]

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]

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]

The identification of hepatitis C virus (HCV) as the causative agent of non-A and non-B hepatitis, over 20 years ago, fueled an intensive effort to develop direct-acting antivirals targeting the viral polymerase and protease, two key proteins critical for HCV replication. However, it took more than two decades for these efforts to be realized with boceprevir, one of the two HCV protease inhibitors approved for treatment of HCV infection in 2011. The development of boceprevir is a major advancement in the ability to treat HCV infection and a significant step toward the long-term goal of eradicating chronic HCV infection. Both as a first-in-class agent and an entirely new modality for treating HCV infection, many challenges were encountered during the discovery and development of this compound. The lessons learned in overcoming these obstacles offer insights and pave the way for the newly emerging field of HCV antiviral therapeutics. This paper will describe the discovery and development of a first-in-class direct antiviral treatment for chronic hepatitis C infection, boceprevir, marketed around the world as VictrelisTM. [ABSTRACT FROM AUTHOR]

This paper describes a new route for the synthesis of 1′-homo- N-nucleoside derivatives by means of either methyltrioxorhenium (MTO) or supported MTO catalysts, with H2O2 as the primary oxidant. Under these selective conditions, the oxyfunctionalization of the heterocyclic ring and the N heteroatom oxidation were operative processes, regardless of the type of substrate used, that is, purine or pyrimidine derivatives. In addition, the oxidation of 1′-homo- N-thionucleosides, showed the occurrence of site-specific oxidative nucleophilic substitutions of the heterocyclic ring. The MTO/H2O2 system showed, in general, high reactivity under both homogeneous and heterogeneous conditions, affording the final products with high conversion values of substrates and from medium to high yields. Many of the novel 1′-homo- N-nucleoside analogues were active against the influenza A virus, without any cytotoxic effects, retaining their activity in both protected and unprotected forms. [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]