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At least 19 recordsLinked to original sources
PubMed2006

Oligonucleotide-based antiviral strategies.

In the age of extensive global traffic systems, the close neighborhood of man and livestock in some regions of the world, as well as inadequate prevention measures and medical care in poorer countries, greatly facilitates the emergence and dissemination of new virus strains. The appearance of avian influenza viruses that can infect humans, the spread of the severe acute respiratory syndrome (SARS) virus, and the unprecedented raging of human immunodeficiency virus (HIV) illustrate the threat of a global virus pandemic. In addition, viruses like hepatitis B and C claim more than one million lives every year for want of efficient therapy. Thus, new approaches to prevent virus propagation are urgently needed. Antisense strategies are considered a very attractive means of inhibiting viral replication, as oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The ensuing targeted destruction of viral RNA should interfere with viral replication without entailing negative effects on ongoing cellular processes. In this review, we will give some examples of the employment of antisense oligonucleotides, ribozymes, and RNA interference strategies for antiviral purposes. Currently, in spite of encouraging results in preclinical studies, only a few antisense oligonucleotides and ribozymes have turned out to be efficient antiviral compounds in clinical trials. The advent of RNA interference now seems to be refueling hopes for decisive progress in the field of therapeutic employment of antisense strategies.

Animals↗
PubMed2004

Antivirals and antiviral strategies.

In recent years, the demand for new antiviral strategies has increased markedly. There are many contributing factors to this increased demand, including the ever-increasing prevalence of chronic viral infections such as HIV and hepatitis B and C, and the emergence of new viruses such as the SARS coronavirus. The potential danger of haemorrhagic fever viruses and eradicated viruses such as variola virus being used as bioterrorist weapons has also increased the profile of antiviral drug discovery. Here, the virus infections for which antiviral therapy is needed and the compounds that are available, or are being developed, for the treatment of these infections are described.

Adenosylhomocysteinase↗
PubMed2006

Potential antivirals and antiviral strategies against SARS coronavirus infections.

There are a number of antivirals as well as antiviral strategies that could be envisaged to prevent or treat severe acute respiratory syndrome (SARS) (or similar) coronavirus (CoV) infections. Targets for the prophylactic or therapeutic interventions include interaction of the spike (S) glycoprotein (S1 domain) with the host cell receptor, fusion of the S2 domain with the host cell membrane, processing of the replicase polyproteins by the virus-encoded proteases (3C-like cysteine protease [3CLpro] and papain-like cysteine protease) and other virus-encoded enzymes such as the NTPase/helicase and RNA-dependent RNA polymerase. Human monoclonal antibody blocking S1 may play an important role in the immunoprophylaxis of SARS. Fusion inhibitors reminiscent of enfuvirtide in the case of HIV may also be developed for SARS-CoV. Various peptidomimetic and nonpeptidic inhibitors of 3CLpro have been described, the best ones inhibiting SARS-CoV replication with a selectivity index greater than 1000. Human interferons, in particular alpha- and beta-interferon, as well as short interfering RNAs could further be pursued for the control of SARS. Various other compounds, often with an ill-defined mode of action but selectivity indexes up to 100, have been reported to exhibit in vitro activity against SARS-CoV: valinomycin, glycopeptide antibiotics, plant lectins, hesperetin, glycyrrhizin, aurintricarboxylic acid, chloroquine, niclosamide, nelfinavir and calpain inhibitors.

Animals↗
PubMed2004

Quantitative analysis of a parasitic antiviral strategy.

We extended a computer simulation of viral intracellular growth to study a parasitic antiviral strategy that diverts the viral replicase toward parasite growth. This strategy inhibited virus growth over a wide range of conditions, while minimizing host cell perturbations. Such parasitic strategies may inhibit the development of drug-resistant virus strains.

Allolevivirus↗
PubMed2026

Coxsackievirus A6 on the rise: epidemiology, pathogenicity, evolutionary dynamics, and antiviral strategy.

SUMMARYIn recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.

Humans↗
PubMed2006

Polyomavirus-associated nephropathy: update on antiviral strategies.

Polyomavirus-associated nephropathy (PVAN) is a major complication of kidney transplantation. Many centers respond to PVAN by reducing immunosuppression. Concern over precipitating rejection, as well as situations in which some PVAN-afflicted individuals have multi-organ transplants, can make reduction of immunosuppression undesirable. In these cases, effective antiviral strategies would be useful. This article describes clinical observations and experiences with 3 different antiviral protocols. Two protocols address antiviral treatment of nephropathy (cidofovir in one, and leflunomide in the other). The third protocol examines fluoroquinolone control of polyoma urinary excretion. Patients responded to all 3 strategies. These promising approaches deserve further evaluation with prospective controlled studies.

Animals↗
PubMed1998

A novel mutant loxP containing part of long terminal repeat of HIV-1 in spacer region: presentation of possible target site for antiviral strategy using site-specific recombinase.

A site-specific recombinase Cre is responsible for the recombination at a 34 bp loxP site. This system has been investigated for the antiviral strategy to excise proviral DNA from retrovirus-infected cells. It was reported that loxP sites could be inserted into long terminal repeat (LTR) of retrovirus to delete proviral DNA. To apply this system to human immunodeficiency virus type 1 (HIV-1) without inserting any DNA, one 34 bp sequence was selected from LTR of recombinant HIV-1 clone, loxLTR-1, based on sequence similarity between LTR and loxP, and sequence arrangement of 8 bp middle part in 34 bp LTR segment. When the 8 bp spacer region of loxP was changed into the corresponding middle part of loxLTR-1, this variant loxP would allow Cre to specifically recombine between themselves but not with wild-type loxP in vitro. This study suggests that site-specific excision of proviral DNA of HIV-1 could be catalyzed by the least modified Cre recognizing the loxLTR-1 sites.

HIV Infections↗
PubMed2003

Quasispecies and the development of new antiviral strategies.

RNA virus populations consist of complex and dynamic mutant distributions, rather than defined genomic sequences. This feature confers great adaptability on viruses and is partly responsible for current difficulties of viral disease prevention and control. Mutant distributions, also termed mutant swarms or mutant clouds, were first proposed in a theory of molecular evolution termed quasispecies theory. The theoretical formulation of quasispecies and its links to present day RNA viruses are discussed. The need to accommodate antiviral strategies to the dynamic nature of viral populations is emphasized. In particular, recent results on viral extinction associated with enhanced mutagenesis (virus entry into error catastrophe) are reviewed and presented as an example of how the understanding of viruses as quasispecies could lead to a potential practical application in medicine.

Animals↗
PubMed2004

Influence of mutations in the hepatitis B virus genome on virus replication and drug resistance--implications for novel antiviral strategies.

Persistent infection with the hepatitis B virus (HBV) represents a major health problem worldwide with over 350 million patients at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double-stranded DNA virus with four overlapping genes and a unique life cycle, creating an intracellular pool of covalently closed circular DNA molecules for persistence and an RNA template for replication via reverse transcription. Mutations occur frequently, and particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antivirals), readily select escape mutants. For example, HBeAg-negative chronic HBV infection with either basal core promoter or precore mutations is predominant in many parts of the world. Therapy of HBV infection with the nucleoside analogue lamivudine frequently leads to the selection of drug-resistant strains with polymerase mutations. Treatment options for chronic HBV infection include at present either interferon-alpha or the oral nucleos(t)ide analogues lamivudine or adefovir. However, these drugs have drawbacks, including possible serious side effects and low response rates in HBeAg-negative patients in the case of interferon or recurrence of viremia after cessation of therapy and development of escape mutants after a long period of treatment with nucleoside inhibitors. Recent advances of in vitro and in vivo models allow to study new antiviral strategies, including novel nucleoside analogues, nucleocapsid inhibitors or small interfering RNA. This review summarises the impact of clinically relevant mutations in the HBV genome on viral replication and drug sensitivity, the current status of therapy and promising future perspectives on novel drug regimens.

Animals↗
PubMed2003

The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies.

By using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), we have identified the arenavirus small RING finger Z protein as the main driving force of virus budding. Both LCMV and Lassa fever virus (LFV) Z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the Gag protein of Rous sarcoma virus. LCMV and LFV Z proteins contain proline-rich motifs that are characteristic of late domains. Mutations in the PPPY motif of LCMV Z severely impaired the formation of virus-like particles. LFV Z contains two different proline-rich motifs, PPPY and PTAP, which are separated by eight amino acids. Mutational analysis revealed that both motifs are required for efficient LFV Z-mediated budding. Both LCMV and LFV Z proteins recruited to the plasma membrane Tsg101, which is a component of the class E vacuolar protein sorting machinery that has been implicated in budding of HIV and Ebola virus. Targeting of Tsg101 by RNA interference caused a strong reduction in Z-mediated budding. These results indicate that Z is the arenavirus functional counterpart of the matrix proteins found in other negative strand enveloped RNA viruses. Moreover, members of the vacuolar protein sorting pathway appear to play an important role in arena-virus budding. These findings open possibilities for antiviral strategies to combat LFV and other hemorrhagic fever arenaviruses.

Amino Acid Sequence↗
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: II. Inhibition of duck hepatitis B virus in vitro using conventional antiviral agents and supercoiled-DNA active compounds.

Primary duck hepatocyte (PDH) cultures, congenitally infected with the duck hepatitis B virus (DHBV), were grown on feeder cell layers of irradiated human embryonic lung fibroblasts and then exposed to a number of compounds with recognized or potential antiviral activity. These compounds included conventional antiviral agents, reverse transcriptase inhibitors, compounds with activity to supercoiled-DNA, and DNA-binding agents. Twenty-three compounds were evaluated, and 13 were found to inhibit significantly viral DNA replication. Seven of these compounds (ellipticine, amsacrine, coumermycin A1, Adriamycin, mitozantrone, chloroquine, and neocarzinostatin) acted at the level of viral SC DNA and significantly inhibited production of duck hepatitis B surface antigen (DHBsAg). Conventional agents that inhibited DHBV DNA replication included ganciclovir, acyclovir, bromovinyldeoxyuridine, ribavirin, phosphonoformate, and dideoxyadenosine. Except for dideoxyadenosine, these inhibitors of viral DNA synthesis did not significantly inhibit DHBsAg production. Two additional compounds, novobiocin and nalidixic acid, altered the pattern of viral DNA replication, especially the generation and processing of viral SC DNA, and also inhibited the production of DHBsAg. Several compounds acting at the level of viral SC DNA have now been identified and may offer potential for the management of chronic hepatitis B virus infection.

Animals↗
PubMed1999

Therapy of chronic hepatitis B virus infection: inhibition of the viral polymerase and other antiviral strategies.

Chronic hepatitis B infection remains a major public health problem worldwide. The hepatitis B virus belongs to the family of hepadnaviruses that replicate their DNA genome via a reverse transcription pathway. The chronicity of infection in infected hepatocytes is maintained by the persistence of the viral covalently closed circular DNA. The main strategies to combat chronic HBV infection rely on the stimulation of the specific antiviral immune response and on the inhibition of viral replication. While the prolonged administration of reverse transcriptase inhibitors is most often associated with a control of viral replication rather than eradication, it may select for resistant mutants. The search for new viral targets is therefore mandatory to design combination strategies to prevent the emergence of resistant mutants and eventually clear viral infection.

Animals↗
PubMed2005

Potential importance of error catastrophe to the development of antiviral strategies for hantaviruses.

Hantaviruses represent an important and growing source of disease emergence in both established and developing countries. The New World hantaviruses have been touted as potential biological weapons because of their lethality to humans and high infectivity as an aerosol. It is also important to acknowledge the threat that hantaviruses can represent to US troops that operate in a foreign territory endemic for hantavirus infection, as was demonstrated in the Korean War. Effective vaccines, immunotherapeutics and antivirals for the prophylaxis or treatment of hantaviral infections are not available. Recent evidence that hantaviruses are prone to error catastrophe opens the door to the development of new therapeutic strategies. Possible future directions for applying lethal mutagenesis as a strategy for the development of novel and more effective antiviral therapies for treatment of hantavirus infections are discussed.

Animals↗
PubMed2000

Toward antiviral strategies that resist viral escape.

We studied the effect on viral growth of drugs targeting different virus functions using a computer simulation for the intracellular growth of bacteriophage T7. We found that drugs targeting components of negative-feedback loops gain effectiveness against mutant viruses that attenuate the drug-target interaction. The greater inhibition of such mutants than of the wild type suggests a drug design strategy that would hinder the development of drug resistance.

Antiviral Agents↗