SEARCH · Search PubMed

Results for “antiviral development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed2004

5th Antiviral Drug Discovery and Development Summit.

The 5th Antiviral Drug Discovery and Development Summit provided an up-to-date snapshot of the ongoing developments in the area. The topics covered ranged from updates on recently launched drugs (Kaletra), Fuzeon) and new investigational inhibitors (T-1249, Reverset, UK-427857, L-870810, PA-457, remofovir, VX-950), to the discovery of new antiviral targets and advances in technologies that may provide the substrate for the next generation of therapeutics. It is apparent from the range of presentations that much of today's efforts are focused on developing new classes of HIV inhibitors (gp41, integrase), while there is also considerable progress in hepatitis C, where a number of inhibitors have or should reach proof-of-concept studies in the coming months. Here we provide the highlights of this meeting, with particular emphasis on the new developments in HIV and hepatitis C virus.

Animals↗

PubMed1988

Antiviral chemotherapy today and tomorrow.

Antiviral chemotherapy has come of age. Several compounds, i.e. amantadine, rimantadine, idoxuridine, trifluridine, vidarabine, acyclovir, ribavirin and azidothymidine, have been licensed for clinical use and other promising compounds may follow soon. The search for new antiviral agents has been boosted by the advent of AIDS, but the activity spectrum of the newly developed antivirals not only spans retroviruses but also various other virus infections, i.e. herpes-, adeno-, pox- and rhinovirus infections. Clinical trials have been started with a variety of these new compounds and the prospects for an effective chemotherapy of several viral diseases certainly look bright.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Synthesis and antiviral activities of some 4,4'-dihydroxytriphenylmethanes.

4,4'-Dihydroxytriphenylmethanes were synthesized using Brønsted acid or Lewis acid in yields of 24-86% as target compounds for developing antiviral agents. Most of the 4,4'-dihydroxytriphenylmethanes showed significant activity against herpes simplex virus type 1 (anti-HSV-1 activity) in a plaque reduction assay. Higher cytotoxicity was observed generally in halogenated 4,4'-dihydroxytriphenylmethanes (2a-d) than in non-halogenated derivatives. The non-halogenated derivative, 4,4',4"-trihydroxy-3"-methoxytriphenylmethane (3), showed remarkable antiviral activity with an EC(50) value of 1.8 microg/ml.

Alkanes↗

PubMed2004

Lethal mutagens: broad-spectrum antivirals with limited potential for development of resistance?

RNA virus populations display extreme sequence variation. It is thought that this heterogeneity is advantageous to the population, permitting adaptation to rapidly changing environments that present varying types and degrees of selective pressure. A consequence of this efficient evolution of RNA viruses is the susceptibility of these viruses to compounds that further increase sequence variation as these agents force the virus into error catastrophe. Therefore, lethal mutagenesis, induction of error catastrophe, represents an important, untapped strategy for development of antiviral agents. This article briefly describes the theoretical and experimental data supporting lethal mutagenesis as an antiviral strategy and discusses host and viral mechanisms for development of resistance to ribavirin, a representative of this class of antiviral agents.

Antiviral Agents↗

PubMed1995

Discovery and in vitro development of AIDS antiviral drugs as biopharmaceuticals.

The goal of developing an effective drug against HIV-1 and AIDS has been approached by several routes, with enough encouraging results to stimulate further efforts. Compounds active against HIV-1 have been discovered for many of the functions in the reproductive cycle recognized as virus-specific targets. Discoveries have been made in cell-based assays as well as mechanistic assays, and the value of both types of assays in the drug discovery process has been discussed. Although the final test of a drug's efficacy comes in the clinical experience, submission of an antiviral compound to an in vitro developmental gauntlet can save much time, effort, expense, and human resource in the in vivo developmental regimen required prior to human use. Emergence of viral resistance to drugs in several structural classes has compromised their clinical efficacy, suggesting that development of other potential drugs in those classes may not be good investments. Strains of HIV-1 resistant to specific compound classes are used to categorize new active discoveries for possible developmental exclusion, and defining the mechanism of action of such a new compound may confirm the discouraging judgement. On the other hand, novel compounds which exhibit a broad range of activity in drug-resistant and other HIV-1 strains deserve greater scrutiny. Clinicians most likely will be hesitant to treat patients with compounds shown to act on virus-cell surface interactions, given the failure in the past of several such compounds in clinical studies. But a compound shown to have a unique and novel mechanism of action will be looked upon more favorably, and surviving other tests of potency, solubility, and stability will be unhesitatingly presented for in vivo development. The partial successes of drugs currently in clinical use against AIDS offers great encouragement that other more-effective, less-toxic drugs will be found. Exquisite techniques for identifying new targets on virus gene products, the selection of compounds on activity paradigms, and the enormous variety of compounds becoming available through synthesis libraries, all offer opportunities for anti-HIV drug discovery, which, in our view, cannot fail to present potent antiviral compounds which will survive the rigorous preclinical and clinical tests leading to a drug effective against AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Biological activity of some thiophosphamide derivatives of alkaloids with respect to influenza virus.

Certain newly synthesized compounds belonging to the class of alkaloid ethylenimines, and those known but not subjected to the test for antiviral selection, were studied. The in vitro, in ovo and in vivo experiments detected the substances (Ukrain, amitozin, colchamine-thiotepa, thiotepa) with developed antiviral effect relative to the influenza A/H3 N2/virus strain Port Chalmers 1/73. In the work we used, 1, 10 and 100 ID50 in 0,1 ml. The virus was injected at 1, 10 and 100 EID50 per embryo. The assessment in vivo was carried out on mice of 16-18 g weight. The LD50 for mice having been determined by the probit-analysis method, therapeutic concentrations were used at 1/10 of the LD50. The preparations were found to possess an inhibitory action for the virus, along with insignificant toxicity for the systems studied. Antigrippe action was revealed by the T alkilic agent, in this case thiophosphamide, in all systems. The comparative study of the main component of the alkaloid sum, and of 2 products of their modification (amitozin and Ukrain), showed promise great for creating remedies using such methods and materials. Especially worthy of attention was the Ukrain preparation, which may be recommended as a potential antiviral remedy with the aim of widening the choice of preparations with an antiviral action.

Alkaloids↗

PubMed1981

Pathogenesis of feline infetious peritonitis: pathologic changes and immunofluorescence.

Feline infectious peritonitis (FIP) was experimentally induced in FIP virus (FIPV) antibody-positive and antibody-negative kittens after challenge exposure to live-virus aerosol. Seropositive kittens developed antiviral immunofluorescence and lesions more rapidly after challenge exposure than did seronegative kittens. In seropositive kittens, FIPV antigen was present in macrophages and large mononuclear cells in tracheobronchial lymph nodes, lungs, and trachea on postchallenge-exposure day (PCD) 2; in liver and spleen on PCD 3; in kidneys and omentum on PCD 4; and subsequently in nasal turbinates, thoracic and abdominal lymph nodes, thymus, bone marrow, parotid salivary gland, eyes, and brain. Initial antiviral immunofluorescence on PCD 2 coincided with the onset of viremia and vascular lesions. Systemic lesions characterized by perivascular necrotizing pyogranulomatous inflammation, phlebitis and thrombosis, fibrinous serositis, and generalized lymphoid necrosis developed on PCD 3 and 4. Coronavirus-like particles were observed by electron microscopy in cytoplasmic vacuoles or smooth endoplasmic reticulum of degenerating macrophages in inflammatory lesions. In seronegative kittens, antiviral immunofluorescence in tracheobronchial lymph nodes was first detected on PCD 5, and viremia occurred on PCD 6. Systemic necrotizing lesions, comparable with those observed in seropositive kittens on PCD 3 or 4, did not occur in seronegative kittens until PCD 13 or 16. In both groups of kittens, initial viral infection in regional lymphoreticular tissue was followed by viremia and infection of macrophages in reticuloendothelial organs (liver, spleen, lymph nodes) and perivascular locations. The accelerated onset of infection and lesions indicative of an Arthus-type reaction in challenge-exposed seropositive vs seronegative kittens further supports the immune-mediated pathogenesis of FIP.

Animals↗

PubMed1999

Paul Ehrlich and O.T. Avery: pathfinders in the search for immunity.

This paper is concerned with the use of passive immunity for the prevention and treatment of infections from a historic perspective, particularly in regard to the research of Paul Ehrlich on diphtheria and that of O.T. Avery on pneumonia. It is timely to reexamine this matter, particularly in regard to virus infections, in view of the difficulties in developing antiviral drugs. In addition, specific antibodies can serve as an alternative therapy for antibiotic resistant microbes. It is worth recalling in the history of vaccine development that success in passive immunity has been the key element in devising a successful strategy to develop a vaccine to produce humoral immunity.

History, 20th Century↗

PubMed2003

Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation. Significant progress has been made in the prevention of CMV disease over the past decade, but prevention of late CMV disease continues to be a challenge in selected high-risk populations. The pretransplantation CMV serostatus of the donor and/or recipient remains an important risk factor for posttransplantation outcome despite the use of antiviral prophylaxis and preemptive therapy; CMV-seropositive recipients of T cell-depleted grafts in particular continue to have a survival disadvantage compared with seronegative recipients with seronegative donors. The risk of developing antiviral drug resistance remains low in most patients; however, in a setting of intense immunosuppression (eg, after transplantation from a haploidentical donor), the incidence may be as high as 8%. Primary CMV infection via blood transfusion can be reduced by the provision of seronegative or leukocyte-depleted blood products; however, a small risk of 1% to 2% of CMV disease remains. Surveillance and preemptive therapy are effective in preventing the sequelae of transfusion-related CMV infection. Indirect immunomodulatory effects of CMV are increasingly recognized in hematopoietic stem cell transplant recipients. Strategies currently being investigated include long-term suppression of CMV with valganciclovir for the prevention of late CMV infection and disease, adoptive transfer of CMV-specific T cells, and donor and recipient vaccination strategies.

Acyclovir↗

PubMed2004

Bioterrorism and emerging infectious disease - antimicrobials, therapeutics and immune-modulators. SARS coronavirus.

The purpose of this meeting was to provide a forum for expert presentations and discussion about the threats of bioterrorism and emerging infectious diseases, and to address the issues relating to epidemics, prevention of infection and treatment of some of these emerging infectious diseases classified as potential agents of bioterror. Included in the talks were state-of-the-art presentations about infectious clone technology and recombinant viruses, pathogen and receptor interactions at the cellular and molecular level, genomic responses to infection, and new information on antiviral mechanisms of action. Severe acute respiratory syndrome (SARS) and progress toward understanding the epidemic was addressed, and other sessions were presented concerning immune therapy and immunopotentiation of disease, siRNA and gene silencing, host responses to pathogen infections, as well as the use of genetic engineering to circumvent and direct the immune response. Many discussions were held and data were presented about possible compounds and new drugs that may have antiviral properties, yet there were few discussions of any available new drugs. This report addresses reverse genetics of SARS virus, as well as its epidemiology, and a host of different recent approaches to developing antivirals effective against SARS, including some potential vaccine candidates. Also presented are hypotheses about the human immune response to SARS infection, as well as immune therapies against botulinum and anthrax toxins. This report also addresses antiviral approaches exploiting siRNAs, and different aspects of the host immune response to many of the different dangerous pathogens discussed at this meeting. Finally, approaches to circumventing and directing the immune response using genetic engineering will be reported.

Adjuvants, Immunologic↗

PubMed1981

Viral-induced leukocyte interferon in vesicle fluid from lesions of recurrent herpes labialis.

Antiviral activity characterized as human interferon (HuIFN) was demonstrated in vesicle fluid from lesions of recurrent herpes labialis in 18 of 19 otherwise healthy patients. High titers (geometric mean, 29,200 units) were present during the early course of lesion development. Antiviral activity in vesicle fluid was neutralized by antibody to leukocyte (types I) HuIFN (HuIFN-alpha) in the eight patients in whom it was tested. These results indicate that HuIFN-alpha is present in the local lesions of recurrent herpes labialis. HuIFN may have a role in the pathogenesis of recurrent herpesvirus infections.

Adult↗

PubMed2005

Real-time detection of virus particles and viral protein expression with two-color nanoparticle probes.

Respiratory syncytial virus (RSV) mediates serious lower respiratory tract illness in infants and young children and is a significant pathogen of the elderly and immune compromised. Rapid and sensitive RSV diagnosis is important to infection control and efforts to develop antiviral drugs. Current RSV detection methods are limited by sensitivity and/or time required for detection. In this study, we show that antibody-conjugated nanoparticles rapidly and sensitively detect RSV and estimate relative levels of surface protein expression. A major development is use of dual-color quantum dots or fluorescence energy transfer nanobeads that can be simultaneously excited with a single light source.

Respiratory Syncytial Viruses↗

PubMed2005

A peptide inhibitor of HIV-1 assembly in vitro.

Formation of infectious HIV-1 involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids after proteolytic disassembly of the Gag shell. We report a 12-mer peptide, capsid assembly inhibitor (CAI), that binds the capsid (CA) domain of Gag and inhibits assembly of immature- and mature-like capsid particles in vitro. CAI was identified by phage display screening among a group of peptides with similar sequences that bind to a single reactive site in CA. Its binding site was mapped to CA residues 169-191, with an additional contribution from the last helix of CA. This result was confirmed by a separate X-ray structure analysis showing that CAI inserts into a conserved hydrophobic groove and alters the CA dimer interface. The CAI binding site is a new target for antiviral development, and CAI is the first known inhibitor directed against assembly of immature HIV-1.

Amino Acid Sequence↗

PubMed2004

Recent advances in the prevention of CMV infection and disease after hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) remains an important pathogen in hematopoietic stem cell transplant (HCT) recipients in the current era of antiviral prophylaxis and preemptive therapy, despite the almost complete elimination of CMV disease during the first 3 months after transplantation. Pretransplant CMV serostatus of the donor and/or recipient remains an important risk factor for poor post-transplant outcome, especially in highly immunodeficient patients (e.g. recipients of ex vivo or in vivo T-cell depletion). Prevention of late CMV disease continues to be a challenge in selected high-risk populations, and indirect immunomodulatory effects of CMV (e.g. invasive bacterial and fungal infections) appear to contribute to the poor outcome. The risk of developing antiviral resistance remains low in most patients; however, in a setting of intense immunosuppression (e.g. after transplantation from a haploidentical donor) the incidence may be as high as 8%. Transfusion-transmitted CMV infection can be reduced by the provision of seronegative or leukocyte-depleted blood products; however, a small risk of 1-2% of CMV disease remains. Surveillance and preemptive therapy is effective in preventing transfusion-related CMV disease. The development of new drugs and immunologic strategies (adoptive transfer of CMV-specific T-cells and donor/recipient vaccination strategies) are important goals for the elimination of the negative impact of CMV in the HCT setting.

Antiviral Agents↗

PubMedDate not supplied

Viral infection and antiviral therapy in the neonatal intensive care unit.

Viral diseases are leading causes of mortality and morbidity among infants requiring care in the neonatal intensive care unit (NICU), with ongoing discoveries of new viral pathology likely to add to the burdens posed. Many viral diseases in NICU infants are undiagnosed or appreciated only late in the course because of subtle or asymptomatic presentation, confusion with bacterial disease, and failure to consider viral disease. We present an overview of viral disease in NICU infants, with emphasis on pharmacologic agents currently employed for prophylaxis and treatment of such diseases. Advances in molecular biology and popular demand to develop antiviral agents for viral diseases (eg, human immunodeficiency virus) offer great promise for the future.

Antibiotic Prophylaxis↗

PubMed1997

Characterization of engineered hepatitis C virus NS3 protease inhibitors affinity selected from human pancreatic secretory trypsin inhibitor and minibody repertoires.

Given the extent of hepatitis C virus (HCV) infection as a worldwide health problem and the lack of effective treatment, the development of anti-HCV drugs is an important and pressing objective. Previous studies have indicated that proteolytic events mediated by the NS3 protease of HCV are fundamental to the generation of an active viral replication apparatus, as unequivocably demonstrated for flaviviruses. As a result, the NS3 protease has become a major target for discovering anti-HCV drugs. To gain further insight into the biochemical and biophysical properties of the NS3 enzyme binding pocket(s) and to generate biological tools for developing antiviral strategies, we decided to engineer macromolecular ligands of the NS3 protease domain. Phage-displayed repertoires of minibodies ("minimized" antibody-like proteins) and human pancreatic secretory trypsin inhibitor were sampled by using the recombinant NS3 protease domain as a ligate molecule. Two protease inhibitors were identified and characterized biochemically. These inhibitors show marked specificity for the viral protease and potency in the micromolar range but display different mechanisms of inhibition. The implications for prospective development of low-molecular-weight inhibitors of this enzyme are discussed.

Amino Acid Sequence↗

PubMed1993

Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production.

Replication of RNA viruses, such as the human immunodeficiency virus (HIV), is dependent upon multiple specific interactions between viral RNAs and viral and cellular proteins. A small molecule that interferes specifically with one or more of these RNA-protein interactions could be an efficacious antiviral agent. Here we show that certain aminoglycoside antibiotics, in particular neomycin B, can block binding of the HIV Rev protein to its viral RNA recognition element. Inhibition appears to be highly selective, resulting from competitive binding of the drug to a small viral RNA region within the Rev-binding site. We further demonstrate that neomycin B can specifically antagonize Rev function in vitro and in vivo and can inhibit production of HIV. Our results establish the feasibility for developing antiviral drugs that act by selectively blocking RNA-protein interactions.

Anti-Bacterial Agents↗

PubMed1984

Induction of lymphosarcoma in sheep inoculated with bovine leukaemia virus.

Five sheep were experimentally inoculated with BLV in order to study the humoral immune response in animals infected with bovine leukaemia virus (BLV). During experimental periods of 46 months, 2 sheep died with leukaemia and one sheep showed splenomegaly and proliferation of tumour cells. The other 2 sheep were clinically normal. All of the inoculated sheep developed antiviral antibodies 1 month after inoculation and BLV could be re-isolated in lymphocytes 2 to 3 months after inoculation. Antibody against glycoprotein antigen (gp51) of BLV appeared earlier than the antibody against protein antigen (p24) and antibody titres of the former were higher than those of the latter during the course of the experiment. The complement dependent antibody cytotoxicity test was performed for the detection of antibody against BLV-related cell membrane antigen with 2 different kinds of target cells; FLK cells which are foetal lamb kidney cells chronically infected with BLV and SF-28 cells which are sheep fibroblasts transformed with BLV in vitro. All 5 sheep developed cytotoxic antibodies against both types of cells. In sera from two leukaemic sheep, cytotoxic antibody titres against SF-28 cells gradually decreased 30 months after inoculation and finally became negative one to 3 months before they died of leukaemia. However, these leukaemic sheep persistently produced antibodies against gp51 and p24.

Animals↗