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Antiviral Drugs (antiviral + drug)
Terms modified by Antiviral Drugs Selected AbstractsTrapping Norovirus by Glycosylated Hydrogels: a Potential Oral Antiviral DrugCHEMMEDCHEM, Issue 12 2006Yalong Zhang Trapped! Hydrogels have potential for use as prophylactic drugs against norovirus infection, as they absorb virus particles with high affinity. Virus entrapped in the hydrogel would be rendered harmless as it is cleared from the body. This approach could be useful in the worldwide fight against viral gastroenteritis outbreaks. [source] 1212: Herpes simplex and zoster keratitisACTA OPHTHALMOLOGICA, Issue 2010M LABETOULLE Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are two leading causes of corneal infection with potential severely impaired visual acuity. These two viruses share multiple characteristics, including the ability to become latent in the trigeminal ganglia, before reactivation and migration along the trigeminal fibers innervating the cornea. The clinical settings of keratitis may vary from an epithelial defect (dendritic of geographic) to a more severe disease involving the stroma and/or the endothelium. Classically, HSV keratitis occurs from the second decade of life, and associated skin disease is not frequent and only involves the eyelids. In contrast, VZV keratitis mostly occurs after the sixth decade, as an associated finding of herpes zoster ophthalmicus (HZO). However, several studies recently highlighted that the rate of HSV keratitis increases with age, even in elderly, and some other studies reported VZV keratitis in children, either isolated or associated with HZO. Antiviral drugs currently available are highly efficient to reduce the severity on ongoing HSV- or VZV keratitis, but preventive treatments still have to be optimized. For HSV keratitis, the usual preventive treatment, as defined by the HEDS study, only reduces the rate of relapses in a two-fold manner, and the optimal dosage has not been settled for patient with severe herpetic disease. For VZV, the two vaccines against chickenpox and HZO probably will lead in the future to a reduction of the incidence of keratitis, but they are not widely used, even in most of developed countries. [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Formation of a defluorinated metabolite of a quinoxaline antiviral drug catalysed by human cytochrome P450 1A2JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2001Peter J. Mutch The in-vitro metabolism of GW420867X ((S)-2-ethyl-7-fluoro-3-oxo-3, 4-dihydro-2H-quinoxaline-1-carboxylic acid isopropyl ester), a quinoxaline drug for the potential treatment of HIV, has been studied with singly expressed human cytochromes P450 (CYP 450). No biotransformation of [14C]GW420867X was evident in the presence of any of the CYP 450 isoforms, with the exception of CYP 450 1A2, where a single metabolite was observed in the HPLC radiochromatograms of enzyme incubations with the test compound. The structure of this metabolite was determined by nuclear magnetic resonance spectroscopy and mass spectrometry, and was shown to correspond to the replacement of the aromatic fluorine of GW420867X with a hydroxyl group. Thus, it appeared that CYP 450 1A2 catalysed the specific defluorination of GW420867X, presumably during formation of an arene oxide intermediate during aromatic hydroxylation. [source] How to diagnose and treat hepatitis B virus antiviral drug resistance in the liver transplant settingLIVER TRANSPLANTATION, Issue S2 2008Anna S. F. Lok Key Points 1Hepatitis B virus variants with antiviral drug,resistant mutations and/or hepatitis B immune globulin,resistant mutations are the main cause of hepatitis B virus reinfections post,liver transplant. 2Early diagnosis of antiviral drug resistance and prompt initiation of rescue therapy are important in preventing hepatitis flares and hepatic decompensation. 3Virologic breakthrough is the first indication of antiviral drug resistance. 4Genotypic resistance testing should be performed when possible to avoid unnecessary modification of treatment in patients who do not have confirmed antiviral drug resistance and to permit appropriate selection of rescue therapy in those who have confirmed antiviral drug resistance. 5Choice of rescue therapy requires knowledge of the past history of hepatitis B virus treatments and virologic response to those treatments, patterns of mutations detected at the time of virologic breakthrough, and in vitro cross-resistance data. 6Occurrence of antiviral drug resistance can be reduced by the use of the most potent nucleos(t)ide analogue(s) with the highest genetic barrier to resistance, emphasis of medication compliance, and close monitoring of virologic response. Liver Transpl 14:S8,S14, 2008. © 2008 AASLD. [source] A review of antiviral therapies in the treatment of cytomegalovirusDERMATOLOGIC THERAPY, Issue 3 2000Adrienne M. Hinkle ABSTRACT: Cytomegalovirus (CMV) is a member of the herpesvirus family that is very prevalent world wide based on serologic testing. In immunocompromised persons CMV produces high rates of morbidity and mortality. Congenital CMV is the leading infectious cause of fetal abnormalities in the United States. Infection of human immunodeficiency virus (HIV) seropositive persons or transplant patients with CMV can produce retinitis, encephalitis, pneumonitis, hepatitis, gastrointestinal ulcerations, and cutaneous lesions. Three intravenous therapies are available for CMV infections: ganciclovir; foscarnet and cidofovir. Most recently a fourth antiviral agent was approved for intravitreal injection. This drug, fomivirsen, is the first antisense oligonucleotide available for therapeutic use. A number of other antiviral drugs and vaccines are currently under study. [source] Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viraemia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV- 1EQUINE VETERINARY JOURNAL, Issue 3 2006G. P. Allen Summary Reasons for performing study: Neurological disease in horses caused by infection with certain ,paralytic' strains of equine herpesvirus-1 (EHV-1) is a potentially devastating condition the pathogenesis of which is poorly understood. Preliminary observations in both experimentally induced and naturally occurring cases of the central nervous system disease have revealed a more robust cell-associated viraemia in horses infected with paralytic isolates of EHV-1, relative to horses infected with abortigenic isolates. To investigate further this pathogenesis - rdevant question, the present study was performed using a greater number of horses and a more precise method for quantification of EHV-1 DNA present in viraemic leucocytes. Objective: To compare the magnitude and duration of leucocyte-associated viraemia in seronegative, age-matched foals following infection with paralytic vs. abortigenic isolates of EHV-1. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 20 weanling foals at 2, 4, 7, 9, 11, 14 and 21 days after intranasal inoculation with either paralytic or abortigenic isolates of EHV-1. The amount of EHV-1 DNA present in each PBMC sample was measured by real-time quantitative PCR. Results: Foals inoculated with paralytic strains of EHV-1 developed both a greater magnitude and longer duration of PBMC-associated viraemia than foals inoculated with abortigenic strains of the virus. Conclusions: Both the higher magnitude and longer duration of cell-associated viraemia contribute to the risk for development of neurological signs in horses infected with paralytic strains of EHV-1. Potential relevance: Our results provide empirically derived, scientific data that contributes to a better understanding of the pathogenetic basis for the differing abilities of paralytic and abortigenic strains of EHV-1 to cause post infection central nervous system disease in the horse. The findings identify the importance of minimising the quantitative burden of viraemic leucocytes that follows exposure to the virus, by the use of effective therapeutic antiviral drugs and efficacious prophylactic vaccines that stimulate cytotoxic immune responses against EHV-1 infected cells. [source] Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudineEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2003Tetsuhiro Chiba Abstract: We report a 38-yr-old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb-positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers. [source] The capsid protein of human immunodeficiency virus: designing inhibitors of capsid assemblyFEBS JOURNAL, Issue 21 2009José L. Neira The mature capsid of human immunodeficiency virus, HIV-1, is formed by the assembly of copies of a capsid protein (CA). The C-terminal domain of CA, CTD, is able to homodimerize and most of the dimerization interface is formed by a single ,-helix from each monomer. Assembly of the HIV-1 capsid critically depends on CA,CA interactions, including CTD interaction with itself and with the CA N-terminal domain, NTD. This minireview reports on the search and the design of peptides and small organic compounds that are able to interact with the CTD and/or CA of HIV-1. Such molecules aim to disrupt and/or alter the oligomerization capability of CTD. The different peptides designed so far interact with CTD mainly via hydrophobic contacts with residues close or belonging to the interface between the dimerization helices. A CTD-binding organic compound also establishes hydrophobic contacts with regions involved in the interface between the NTD and CTD. These results open new venues for the development of new antiviral drugs that are able to interact with CA and/or its domains, hampering HIV-1 assembly and infection. [source] Emerging clinical concerns in the ageing haemophilia patientHAEMOPHILIA, Issue 6 2009B. A. KONKLE Summary., The availability of safe replacement clotting factor concentrates together with effective antiviral drugs to treat human immunodeficiency and hepatitis C viruses and the provision of care at designated haemophilia treatment centres have resulted in a new phenomenon in haemophilia management , the ageing patient. Today, increasing numbers of persons with haemophilia (PWH) are middle-aged and older, and they face the same age-related health issues as the general population. The impact of these risks on PWH is unclear, however, and there is a paucity of information about how to manage comorbidities in this patient population. This review focuses on five comorbidities that uniquely affect older PWH: cardiovascular disease, liver disease, cancer, renal disease and joint disease. Available research is summarized and potential management approaches are suggested. [source] Investment in antiviral drugs: a real options approachHEALTH ECONOMICS, Issue 10 2010Arthur E. Attema Abstract Real options analysis is a promising approach to model investment under uncertainty. We employ this approach to value stockpiling of antiviral drugs as a precautionary measure against a possible influenza pandemic. Modifications of the real options approach to include risk attitude and deviations from expected utility are presented. We show that risk aversion counteracts the tendency to delay investment for this case of precautionary investment, which is in contrast to earlier applications of risk aversion to real options analysis. Moreover, we provide a numerical example using real world data and discuss the implications of real options analysis for health policy. Suggestions for further extensions of the model and a comparison with the expected value of information analysis are put forward. Copyright © 2009 John Wiley & Sons, Ltd. [source] Viral loads of herpes simplex virus in clinical samples,A 5-year retrospective analysis,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2010Julian W. Tang Abstract Viral loads of herpes simplex virus (HSV) are not monitored usually for the effective clinical management of HSV-related diseases. However, recently, there has been more interest about the typical HSV levels in clinical specimens, and how such data may improve understanding of the behavior of this virus in such clinical presentations, particularly in immunocompromised patients, where more prolonged therapy using higher doses of antiviral drugs may be required. Using an in-house quantitative HSV-1/HSV-2 polymerase chain reaction assay, an observational, retrospective 5-year analysis of diagnostic, quantitative HSV-1 and HSV-2 DNA levels was conducted. The results (all in median log10 DNA copies/ml), including perhaps the first quantitative comparison of cerebrospinal fluid (CSF) HSV viral loads, were as follows: CSF: HSV-1, 3.40 (range 2.30,8.98) versus HSV-2, 3.60 (range 2.31,6.86) (P,=,0.559); plasma: HSV-1, 3.20 (range 2.23,5.51) versus HSV-2, 3.20 (range 3.18,3.41) (P,=,0.905); genital swabs: HSV-1, 6.79 (range 2.28,8.48) versus HSV-2, 6.97 (range 3.40,9.66) (P,=,0.810); oral swabs: HSV-1, 7.28 (range 2.46,10.04) versus HSV-2, 5.62 (range 4.60,6.63) (P,=,0.529). Note that with the samples usually collected for HSV testing (i.e., CSF, plasma, oral, and genital swabs) there was no significant difference in the viral loads between HSV-1 and HSV-2 types, nor between immunocompetent and immunocompromised patients for each of these different HSV types. Indeed, even between immunocompromised patients with similar diseases, for these samples, the HSV loads were found to vary considerably. These findings may therefore limit the usefulness of monitoring HSV loads in everyday clinical practice. J. Med. Virol. 82:1911,1916, 2010. © 2010 Wiley-Liss, Inc. [source] Role of long-term lamivudine treatment of hepatitis B virus recurrence after liver transplantationJOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Hyun Young Woo Abstract In this study, the long-term (>3 years) efficacy of combination therapy for hepatitis B virus (HBV) recurrence and the associated factors were investigated. One hundred and sixty-five consecutive HBsAg-positive patients (92 with liver cirrhosis, 73 with hepatocellular carcinoma; HCC) who underwent liver transplantation were assessed with a median follow-up time of 40 months. One hundred and twenty-one patients (121/165, 73.3%) were treated with lamivudine before transplantation for a mean of 8.4 months (range 0.1,72 months). The post-transplantation treatment protocol consisted of a high dose intravenous hepatitis B immunoglobulin (HBIg) followed by a low dose intramuscular HBIg and lamivudine combination therapy. Seven (4.2%, 7/165) recipients experienced HBV recurrence at a median time of 19 months (range 5,36 months) following transplantation. Six of seven cases of HBV recurrence were treated with lamivudine before transplantation for a median period of 15 months (range 0.6,30 months). Eighteen (24.6%, 18/73) patients had HCC recurrences after transplantation. Of the four patients with both HCC and HBV recurrence, three experienced HBV recurrence after recurrence of HCC. The clinical factor associated with HBV recurrence in the total cohort (n,=,165) was the duration of antiviral treatment (over 6 months) before transplantation (P,=,0.004). In the HCC group, HCC recurrence after transplantation (P,=,0.002), tumor burden before transplantation (P,=,0.005), and postoperative adjuvant chemotherapy (P,=,0.002), were additional factors for HBV recurrence. Combination therapy of HBIg and antiviral drugs was effective over 3 years regardless of the pretransplantation viral load. However, the possible recurrence of HBV needs to be monitored cautiously in patients treated with long-term (over 6 months) lamivudine. J. Med. Virol. 80:1891,1899, 2008. © 2008 Wiley-Liss, Inc. [source] Suppression of hepatitis C virus replication by protein kinase C-related kinase 2 inhibitors that block phosphorylation of viral RNA polymeraseJOURNAL OF VIRAL HEPATITIS, Issue 10 2009S.-J. Kim Summary., Hepatitis C virus (HCV) infection is a serious threat to human health worldwide. In spite of the continued search for specific and effective anti-HCV therapies, the rapid emergence of drug-resistance variants has been hampering the development of anti-HCV drugs designed to target viral enzymes. Targeting host factors has therefore emerged as an alternative strategy offering the potential to circumvent the ever-present complication of drug resistance. We previously identified protein kinase C-related kinase 2 (PRK2) as a cellular kinase that phosphorylates the HCV RNA-dependent RNA polymerase (RdRp). Here, we report the anti-HCV activity of HA1077, also known as fasudil, and Y27632, which blocks HCV RdRp phosphorylation by suppressing PRK2 activation. Treatment of a Huh7 cell line, stably expressing a genotype 1b HCV subgenomic replicon RNA, with 20 ,m each of HA1077 and Y27632 reduced the HCV RNA level by 55% and 30%, respectively. A combination of the inhibitors with 100 IU/mL interferon , (IFN-,) significantly potentiated the anti-HCV drug activities resulting in approximately a 2-log10 viral RNA reduction. We also found that IFN-, does not activate PRK2 as well as its upstream kinase PDK1 in HCV-replicating cells. Furthermore, treatment of HCV-infected cells with 20 ,m each of HA1077 and Y27632 reduced the levels of intracellular viral RNA by 70% and 92%, respectively. Taken together, the results identify PRK2 inhibitors as potential antiviral drugs that act by suppressing HCV replication via inhibition of viral RNA polymerase phosphorylation. [source] Mass spectrometry analysis of the influenza virus,MASS SPECTROMETRY REVIEWS, Issue 1 2009Kevin M. Downard Abstract The role of mass spectrometry to probe characteristics of the influenza virus, and vaccine and antiviral drugs that target the virus, are reviewed. Genetic and proteomic approaches have been applied which incorporate high resolution mass spectrometry and mass mapping to genotype the virus and establish its evolution in terms of the primary structure of the surface protein antigens. A mass spectrometric immunoassay has been developed and applied to assess the structure and antigenicity of the virus in terms of the hemagglutinin antigen. The quantitation of the hemagglutinin antigen in vaccine preparations has also been conducted that is of importance to their efficacy. Finally, the characterization and quantitation of antiviral drugs against the virus, and their metabolites, have been monitored in blood, serum, and urine. The combined approaches demonstrate the strengths of modern mass spectrometric methods for the characterization of this killer virus. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 28:35,49, 2009 [This article was published online 10 September 2008. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 7 November 2008.] [source] The discovery of antiviral agents: Ten different compounds, ten different stories,MEDICINAL RESEARCH REVIEWS, Issue 6 2008Erik De Clercq Abstract This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 6, 929,953, 2008 [source] Selective human enterovirus and rhinovirus inhibitors: An overview of capsid-binding and protease-inhibiting moleculesMEDICINAL RESEARCH REVIEWS, Issue 4 2004Shin-Ru Shih Abstract The absence of effective vaccines for most viral infections highlights an urgent necessity for the design and development of effective antiviral drugs. Due to the advancement in virology since the late 1980s, several key events in the viral life cycle have been well delineated and a number of molecular targets have been validated, culminating in the emergence of many new antiviral drugs in recent years. Inhibitors against enteroviruses and rhinoviruses, responsible for about half of the human common colds, are currently under active investigation. Agents targeted at either viral protein 1 (VP1), a relatively conserved capsid structure mediating viral adsorption/uncoating process, or 3C protease, which is highly conserved among different serotypes and essential for viral replication, are of great potential to become antipicornavirus drugs. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 4, 449,474, 2004 [source] IL-10 and the resolution of infections,THE JOURNAL OF PATHOLOGY, Issue 2 2008CM Filippi Abstract Chronic viral infections pose serious health concerns, as secondary complications such as immunodeficiencies and cancers are common. Treating such infections with conventional vaccine approaches has proved to be difficult. Studies in animals and humans suggest that vaccine failure is probably due to exhaustion of antiviral T cell responses, which occurs in a number of chronic infections. Attempts to elucidate the causes of impairment of antiviral immunity have pointed to a role for the immunomodulatory cytokine IL-10 in the ability of viruses to establish persistence. Induction of IL-10 production by the host during chronic infection appears to be one of the viral means to alter the class of the antiviral immune response and induce generalized immune suppression. Recent work by us and others suggests that it is possible to resuscitate antiviral immunity by interfering with the IL-10 signalling pathway. Targeting IL-10 thus constitutes a promising alternative to conventional vaccine strategies which have not proved to be successful in treating chronic infections. In addition, sterile cure may be achieved with minimal side-effects by combining agents that alter the IL-10 signalling pathway with other compounds, such as antiviral drugs or interferon, but also agents neutralizing other crucial elements of T cell exhaustion, such as PD-1. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Rituximab monotherapy, rather than rituximab plus antiviral drugs, for initial treatment of severe hepatitis C virus,associated mixed cryoglobulinemia syndrome: Comment on the article by Terrier et alARTHRITIS & RHEUMATISM, Issue 3 2010Salvatore De Vita MD No abstract is available for this article. [source] Modelling strategic use of the national antiviral stockpile during the CONTAIN and SUSTAIN phases of an Australian pandemic influenza responseAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2010Jodie McVernon Abstract Objective: To define optimum use of the national antiviral stockpile during the early phases of the response to pandemic influenza in Australia, to inform the 2008 revision of the Australian Health Management Plan for Pandemic Influenza. Methods: A mathematical model was used to compare strategic uses of antiviral agents for treatment and post-exposure prophylaxis to limit transmission until availability of a strain-specific vaccine. The impact of provision of pre-exposure prophylaxis to healthcare workers (HCWs) on the ability to control the epidemic was also assessed. Results: Optimal constraint of epidemic growth was achieved by intensive ascertainment of contacts of cases for post-exposure prophylaxis for as long as feasible. While pre-exposure prophylaxis of healthcare workers utilised a substantial proportion of the stockpile, this did not impede disease control or the ability to treat cases. Absolute delays to outbreak depended on both the intervention strategy and the growth rate of the epidemic. As vaccination was only effective when introduced before explosive growth, this timing was critical to success. Conclusions and implications: Liberal distribution of antiviral drugs to limit disease spread for as long as is feasible represents optimal use of these agents to constrain epidemic growth. In reality, additional non-pharmaceutical control measures are likely to be required to control transmission until vaccines can definitively contain pandemic influenza outbreaks. [source] Crystallization and preliminary X-ray analysis of the human respiratory syncytial virus nucleocapsid proteinACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2008K. El Omari Human respiratory syncytial virus (HRSV) has a nonsegmented negative-stranded RNA genome which is encapsidated by the HRSV nucleocapsid protein (HRSVN) that is essential for viral replication. HRSV is a common cause of respiratory infection in infants, yet no effective antiviral drugs to combat it are available. Recent data from an experimental anti-HRSV compound, RSV-604, indicate that HRSVN could be the target site for drug action. Here, the expression, purification and preliminary data collection of decameric HRSVN as well as monomeric N-terminally truncated HRSVN mutants are reported. Two different crystal forms of full-length selenomethionine-labelled HRSVN were obtained that diffracted to 3.6 and ,5,Å resolution and belonged to space group P212121, with unit-cell parameters a = 133.6, b = 149.9, c = 255.1,Å, and space group P21, with unit-cell parameters a = 175.1, b = 162.6, c = 242.8,Å, , = 90.1°, respectively. For unlabelled HRSVN, only crystals belonging to space group P21 were obtained that diffracted to 3.6,Å. A self-rotation function using data from the orthorhombic crystal form confirmed the presence of tenfold noncrystallographic symmetry, which is in agreement with a reported electron-microscopic reconstruction of HRSVN. Monomeric HRSVN generated by N-terminal truncation was designed to assist in structure determination by reducing the size of the asymmetric unit. Whilst such HRSVN mutants were monomeric in solution and crystallized in a different space group, the size of the asymmetric unit was not reduced. [source] | |||||||||||||