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Antiviral therapy.

The current status of antiviral therapy is reviewed, including discussion of older approaches together with more recently developed chemotherapy. Following the introduction dealing with pathophysiological aspects of virus disease, the different approaches to antiviral therapy are presented. The reasons for the slow progress in antiviral therapy are discussed. These include: 1. the necessity of intracellular penetration of drugs acting on viral replication; 2. the severe toxicity of most antiviral drugs; 3. the narrow antiviral spectrum of most of these agents; 4. the difficulty of making a rapid etiological diagnosis in view of the necessity of starting (specific?) treatment early in the course of the disease; 5. the difficult evaluation of beneficial as compared with deleterious effects of antiviral therapy. After a detailed review of clinically tested substances, including immunoglobulins, synthetic antiviral drugs (amantadine, nucleoside analogs, thiosemicarbazones and photodynamic dyes) and interferon, a guide concerning indications and application of specific antiviral therapy is presented. Although at present there are few indications, clinicians should be aware of the (present and future) possibilities of antiviral therapy.

Antibodies, Viral↗
PubMed1977

The natural history of recurrent herpes simplex labialis: implications for antiviral therapy.

We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease.

Administration, Topical↗
PubMed1978

[Antiviral therapy of herpetic lesions of the nervous system].

The authors discuss some results of their study concerning the therapeutical effectiveness of different drugs and methods in treating herpes. A total of 194 patients were observed. In 73 cases desoxyribonuclease, interferon, inductors of interferon were used (viruses of ECHO of type 1 and 12, polyomyelitis vaccine, yeast ribonucleinic acid were used as inductors). Antiviral therapy permitted to prevent the development of postherpetic neuralgia, decrease the duration of hospitalization and in cases of remittent development either arrest or significantly reduce the number of relapses and clinical signs. The authors propose a scheme in the treatment of neurological forms of herpes. Further search for effective treatment is discussed.

Deoxyribonucleases↗
PubMed1979

[Present state of antiviral therapy (author's transl)].

Application of antiviral drugs in viral infections is still limited to few diseases. Most of the preparations available induce strong side effects since these substances not only interfere with virus replication but also with cell metabolism. Therefore, only in severe diseases such as herpes simplex encephalitis or complications of varizella zoster infection such a treatment is advisable. From a clinical point of view an antiviral drug would be desirable which selectively inhibitis virus growths without affecting the host. This can already be achieved with interferon. However, at the present time the quantities of interferon needed for such treatment are not available.

Amantadine↗
PubMed2026

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

Humans↗
PubMed1976

The need for antiviral therapy and prophylaxis of viral ocular disease.

The cost of development of a compound with clinical potential as an antiviral agent is so great that it cannot be undertaken unless there is likely to be a market that will return the investment. The current practice, assessment of the prospect on the basis of the present market for idoxuridine and calculation of a likely percentage of capture by a potentially superior compound, is basically erroneous and may lead to gross underestimates of the market. In addition to the market for agents effective in treatment of dendritic and amoeboid ulcers, there is a potentially much greater market, first, for somewhat less toxic compounds that may be used more or less continuously over very long periods for prevention of recurrences. Substances with promise of filling each of these requirements are already under investigation. There is also a potential market for therapeutic preparations with activities against a range of agents, particularly herpesviruses, adenoviruses, and chlamydiae, that commonly cause follicular conjunctivitis or keratoconjunctivitis.

Antiviral Agents↗
PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗
PubMed1976

Ocular antiviral therapy in perspective.

The eye presents a unique model for the study of the pathogenesis of viral disease, drugs, and local and general host factors. Disease is easily observed and quantitated, and the presence of two organs sometimes permits controlled observations that are otherwise impossible. Perhaps most important, ocular viral infection is disabling and blinding, and the success of its treatment with antiviral drugs has clearly demonstrated the potential for the use of antiviral drugs in other areas.

Animals↗
PubMed1975

Recent advances in antiviral therapy.

It has been demonstrated in clinical trials that (1) the antimetabolites Ara A and F3T are both significantly better than IDU in the treatment of many forms of ocular herpes, and (2) they are not significantly different from each other. In preclinical trials, the IDU ocular insert also has shown itself to be significantly better than IDU drop-ointment therapy, while exposing the eye to 40 percent less drug and adding tremendous convenience and ease of compliance by patients to an otherwise difficult medication schedule. Both photodynamic inactivation and cryotherapy have been shown in clinical trials to have notable therapeutic efficacy against herpes, but undesirable and occasionally severe side-effects have slowed down and possibly stopped the further development of these techniques.

Antiviral Agents↗
PubMed1992

[Acute necrotizing retinitis with amotio retinae. Surgical and medicamentous antiviral therapy].

This report pertains to the case of a 25-year-old patient suffering from acute necrotizing retinitis (ANR syndrome). Initially, one eye revealed clinical signs of diffuse chorioretinitis accompanied by perivasculitis and heavy keratic precipitates, papillitis, and vitreous infiltrates. After initial improvement under antiphlogistic therapy, however, necrotizing retinitis developed, associated with peripapillar hemorrhages, multiple peripheral retinal holes and eventually complete retinal detachment. The subsequently performed retinal detachment surgery, completed with vitrectomy, cerclage and silicone oil tamponade, was successful. At the same time, the patient was put on systemic therapy based on acyclovir. In the literature, similar developments are usually related to HSV and HZV infections. Although in our case a virological diagnostic test did not reveal the presence of any virus, the characteristic symptoms of the ANR syndrome completely disappeared under the above-mentioned therapy. Visual acuity, previously consisting only in light perception, improved to 0.4.

Acyclovir↗
PubMed2025

Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.

Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. FGF21, RPTOR, and IFNL3/4). Fifteen cirrhosis loci exhibited differential effects on cirrhosis risk via underlying etiologies, and six HCC loci influenced HCC risk indirectly via cirrhosis. In a gene-burden analysis of rare variants from whole-genome sequencing data in the VA Million Veteran Program (n=102,677), we identified GSTA5 as a novel cirrhosis-associated gene, while APOB and ATP9B were associated with and replicated for HCC. A high genetic risk score for cirrhosis was associated with a nearly doubled risk of CLD progressing to cirrhosis (HR=1.94, P=2×10-68) and of cirrhosis progressing to HCC (HR=1.65, P=7×10-08). Finally, among individuals with chronic hepatitis C who underwent antiviral therapy, cirrhosis risk was modified by variants in PNPLA3, IFNL3/4, and CD81 following pegylated interferon-α therapy, and by APOE lead variant following direct-acting antiviral therapy. These findings provide new insights into the complex genetic architecture of CLD progression with potential clinical and therapeutic implications.

Journal Article↗
PubMed1976

Herpes encephalitis. Rapid diagnosis and treatment with antiviral drugs.

The use of specific IgM antibodies and direct electron-microscopic examination of brain biopsies or vesicle fluid was tested as means of raped diagnosis in 6 cases of herpes simplex encephalitis seen consecutively in Montreal. In 2 of 3 biopsies herpes viruses were seen by negative staining of a cell extract within 1 hr. In the negative case, the biopsy was done almost 1 month after onset. In 2 additional cases herpes virus particles were found directly in the fluid of isolated vesicles. In the last 2 cases, who survived, the diagnosis of herpes encephalitis rested upon the demonstration of a greater than 4-fold rise in complement fixing herpes simplex virus antibodies in convalescent sera and upon the appearance late in the course of the encephalitis of specific antibodies in the cerebrospinal fluid. The early appearance of specific IgM antibodies contributed to the diagnosis in 4 of the 6 cases. Antiviral therapy was attempted in alternate cases (3 cases) but was not successful. Brain biopsy is rarely performed for diagnostic purposes but when prompt antiviral therapy is contemplated, the examination of the biopsy material for herpes virus particles by electron microscopy in negative staining and thin sections can rapidly and reliably confirm the diagnosis.

Aged↗
PubMed2026

Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory condition that can be triggered by viral infections. However, influenza is not commonly recognized as a cause of HLH, and there is no comprehensive synthesis of influenza-associated HLH in the literature to guide clinicians. We conducted a systematic search of Pubmed and Embase to identify case reports and case series on influenza-associated HLH, and included 29 articles involving 47 patients. Their age ranged from 2 months to 72 years. 67% were males. Influenza A accounted for 91.3% of the cases, predominantly H1N1 (90.2%). All patients had fever, 60% had anemia, 69.7% had thrombocytopenia, 46.6% had leukopenia, 61.3% had splenomegaly, 71.4% had hypertriglyceridemia, and 94.7% had elevated ferritin levels. 97.6% had hemophagocytosis on biopsy. Antiviral therapy was administered in 89.5% of patients. HLH-directed therapy included corticosteroids (77%), intravenous immunoglobulin (36%), and etoposide (23.1%). Intensive care was required in 95.2% of cases. Overall survival was 53.2%. Survival rate was 50% among patients who received either antiviral therapy alone or HLH-directed therapy alone, compared with 65.4% among those who received both. Further studies are necessary to establish standardized diagnostic and therapeutic protocols for influenza-associated HLH.

Humans↗