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Reviews in Medical Virology Jan 2024This review assesses the antiviral potential of melatonin through comprehensive analysis of studies across human subjects, animal models, cell cultures, and in-silico... (Review)
Review
This review assesses the antiviral potential of melatonin through comprehensive analysis of studies across human subjects, animal models, cell cultures, and in-silico simulations. The search strategy targeted relevant research until 22 June 2023, resulting in 20 primary studies after screening and deduplication. The findings highlight strong evidence supporting antiviral properties of melatonin. In silico studies identify melatonin as a candidate against SARS-CoV-2, reducing cytokine storm-related respiratory responses. Cell culture experiments reveal its multifaceted effects on different viruses including respiratory syncytial virus, anti-dengue virus, transmissible gastroenteritis virus, and encephalomyocarditis virus. Animal studies show melatonin reduces mortality and viral replication in various infections such as Venezuelan equine encephalomyelitis and COVID-19. Clinical trials show how it could be evaluated, but with no conclusive evidence of efficacy and safety so far from large, double-blind placebo-controlled trials. These insights showcase the potential of melatonin as a versatile antiviral agent with immunomodulatory, antioxidant, anti-inflammatory and antiviral properties. In summary, our review highlights melatonin's promising antiviral properties across diverse settings. Melatonin's immunomodulatory and antiviral potential makes it a compelling candidate for further investigation, emphasising the need for rigorous clinical trials to establish its safety and efficacy against viral infections.
Topics: Animals; Humans; Antiviral Agents; COVID-19; Melatonin; Randomized Controlled Trials as Topic; SARS-CoV-2; Virus Diseases
PubMed: 38126924
DOI: 10.1002/rmv.2499 -
American Journal of Preventive Medicine Dec 2023The hepatitis C virus (HCV) epidemic remains a public health problem worldwide. A systematic review and meta-analysis were conducted to provide evidence of outcomes... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The hepatitis C virus (HCV) epidemic remains a public health problem worldwide. A systematic review and meta-analysis were conducted to provide evidence of outcomes attained across the HCV care cascade in the era of direct-acting antivirals.
METHODS
Studies from North America, Europe, and Australia (January 2014 through March 2021) reporting on HCV care cascade outcomes (screening to cure) were included. When calculating the proportions of individuals completing each step, the numerator for Steps 1-8 was the number of individuals completing each step; the denominator was the number of individuals completing the previous step for Steps 1-3 and Step 3 for Steps 4-8. In 2022, random effects meta-analyses were conducted to estimate pooled proportions with 95% CIs.
RESULTS
Sixty-five studies comprising 7,402,185 individuals were identified. Among individuals with positive HCV ribonucleic acid test results, 62% (95% CI=55%, 70%) attended their first care appointment, 41% (95% CI=37%, 45%) initiated treatment, 38% (95% CI=29%, 48%) completed treatment, and 29% (95% CI=25%, 33%) achieved cure. HCV screening rates were 43% (95% CI=22%, 66%) in prisons or jails and 20% (95% CI=11%, 31%) in emergency departments. Linkage to care rates were 62% (95% CI=46%, 75%) for homeless individuals and 26% (95% CI=22%, 31%) for individuals diagnosed in emergency departments. Cure rates were 51% (95% CI=30%, 73%) in individuals with substance use disorder and 17% (95% CI=17%, 17%) in homeless individuals. Cure rates were lowest in the U.S.
DISCUSSION
Despite the availability of effective all-oral direct-acting antiviral therapies, persistent gaps remain across the HCV care cascade, especially among traditionally marginalized populations. Public health interventions targeting identified priority areas (e.g., emergency departments) may improve screening and healthcare retention of vulnerable populations with HCV infection (e.g., substance use disorder populations).
Topics: Humans; Hepacivirus; Antiviral Agents; Hepatitis C, Chronic; Hepatitis C; Substance-Related Disorders
PubMed: 37380088
DOI: 10.1016/j.amepre.2023.06.016 -
Zeitschrift Fur Naturforschung. C,... Sep 2023Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack... (Review)
Review
Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack SOCSs to inhibit Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, block the production and signaling of interferons (IFNs). At the same time, viruses can hijack SOCS to regulate non-IFN factors to evade antiviral response. Host cells can also regulate SOCSs to resist viral infection. The competition of the control of SOCSs may largely determine the fate of viral infection and the susceptibility or resistance of host cells, which is of significance for development of novel antiviral therapies targeting SOCSs. Accumulating evidence reveal that the regulation and function of SOCSs by viruses and host cells are very complicated, which is determined by characteristics of both viruses and host cell types. This report presents a systematic review to evaluate the roles of SOCSs in viral infection and host antiviral responses. One of messages worth attention is that all eight SOCS members should be investigated to accurately characterize their roles and relative contribution in each viral infection, which may help identify the most effective SOCS to be used in "individualized" antiviral therapy.
Topics: Humans; Virus Diseases; Antiviral Agents; Signal Transduction; Immunity, Innate
PubMed: 37233326
DOI: 10.1515/znc-2023-0024 -
Survey of Ophthalmology 2024Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly... (Meta-Analysis)
Meta-Analysis Review
Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).
Topics: Humans; Retinal Necrosis Syndrome, Acute; Antiviral Agents; Acyclovir; Eye Infections, Viral; Retinal Detachment; Retrospective Studies
PubMed: 37774799
DOI: 10.1016/j.survophthal.2023.09.004 -
Ophthalmic Epidemiology Jun 2024Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify... (Review)
Review
PURPOSE
Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify and compare interventions for treating HSK and their patient outcomes.
METHODS
This systematic review followed the PRISMA methodology. Online databases were searched to obtain all relevant papers. Two independent reviewers screened through 168 records. Seven papers were included and used for data extraction. A qualitative analysis was conducted.
RESULTS
HSK patients receiving prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared to patients receiving only acyclovir ( < .001). No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93% and 67% of patients, and BCVA (LogMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine-A ( < .001) and its control (prednisolone) groups ( = .002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group ( < .001).
CONCLUSION
Corticosteroids and antivirals managed HSK most effectively only when used concurrently. Oral acyclovir showed similar effectiveness to its ointment counterpart, a preferable alternative for easier administration. Corticosteroid use could induce greater therapeutic benefits when tapered in concentration and frequency and administrated for at least 10 weeks. Anti-inflammatory drugs including flurbiprofen, cyclosporine-A, and tacrolimus could be safe and effective for treating HSK. Future long-term follow-up and RCTs could provide insights on the therapeutic benefits of these potential alternatives.
Topics: Humans; Keratitis, Herpetic; Antiviral Agents; Anti-Inflammatory Agents; Glucocorticoids; Acyclovir; Corneal Stroma
PubMed: 37184084
DOI: 10.1080/09286586.2023.2213324 -
Alimentary Pharmacology & Therapeutics Oct 2022The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers.
AIM
To determine the prevalence of HBVr with TNF alpha inhibitors, ustekinumab and vedolizumab METHOD: We followed the MOOSE guidelines and conducted a comprehensive literature search. We conducted a systematic search of EMBASE (Ovid), MEDLINE (Ovid) and PubMed. The studies included patients who were chronic and occult HBV carriers with various rheumatological, dermatological or gastroenterological conditions. We used a random effects model using pooled estimates (prevalence of HBVr with 95% confidence intervals (CI)).
RESULTS
We included 29 studies with 1409 patients infected with HBV. The prevalence of HBVr in chronic carriers of HBV was 17.1% (95% CI: 7.0-35.9, n = 5), 16.6% (95% CI: 9.5-27.5%, n = 6), 40.5% (95% CI: 20.3-64.5%, n = 4) and 19.1% (95% CI: 7.3-41.2%, n = 2), respectively, for adalimumab, etanercept, infliximab and ustekinumab. The respective prevalence for reactivation in patients with occult HBV infection was 5.0% (95% CI: 2.8-8.7%, number of studies: n = 18), 2.6% (95% CI: 1.4-4.7%, n = 18), 4.4% (95% CI: 2.2-8.7%, n = 12) and 6.4% (95% CI: 2.2-16.8, n = 5). There were 39 HBVr (26 in chronic HBV and 13 in the occult group) without any hepatic failure or death. In the chronic HBVr group, only three of 24 patients received antiviral prophylaxis.
CONCLUSIONS
HBVr prevalence rates differ between the chronic carrier state and the occult carrier state. The uptake of prophylactic antiviral therapy in high-risk groups was low, contrary to clinical practice guidelines.
Topics: Antiviral Agents; Biological Therapy; Hepatitis B; Hepatitis B virus; Humans; Ustekinumab; Virus Activation
PubMed: 35975904
DOI: 10.1111/apt.17155 -
Journal of Neurology Mar 2022Antiviral treatments for Bell palsy have been widely used, but there is no definite conclusion of which is the most effective antiviral drug. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antiviral treatments for Bell palsy have been widely used, but there is no definite conclusion of which is the most effective antiviral drug. We conducted a systematic review of randomized controlled trials (RCTs) including network meta-analysis to investigate the comparative effectiveness of antiviral treatments for Bell palsy.
DATA
RCTs comparing effectiveness between antiviral treatments and placebo were included. Risk of bias within and across studies was assessed with the Cochrane tool and the GRADE approach, respectively. Random-effects pairwise meta-analyses were conducted, followed by network meta-analysis.
SOURCES
Three electronic databases were searched from inception to May 18, 2020.
STUDY SELECTION
11 trials and 3393 patients with four arms and eleven contrasts were included.
RESULTS
Significant differences were observed between placebo and famciclovir with respect to overall recovery and no statistically significant differences were found from other comparisons. Treatment ranking based on the evidence network indicated that famciclovir shared the best results, followed by valacyclovir, acyclovir, and finally placebo. Adverse events of famciclovir were too rare and slight to be analyzed. Our confidence in pairwise comparisons was moderate to low, due to study limitations, inconsistency, and imprecision; our confidence in ranking was moderate, due to study limitations. Inconsistency is not deemed to exist by a loop-specific approach and node-splitting procedure. Results of exploring publication bias are satisfying.
CONCLUSIONS
According to pairwise and network comparisons, famciclovir could be better than placebo and the effectiveness of other antiviral treatments are similar. For clinical efficacy, famciclovir obtains the best recovery rate of facial function for Bell palsy. Acyclovir has the lowest rate of synkinesis, though, it is not adequately recommended and more superior trails are needed in the future.
Topics: Acyclovir; Antiviral Agents; Bell Palsy; Humans; Network Meta-Analysis; Valacyclovir
PubMed: 33674936
DOI: 10.1007/s00415-021-10487-9 -
The Journal of Evidence-based Dental... Mar 2023To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials.
METHODS
A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA).
RESULTS
A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only.
CONCLUSION
NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.
Topics: Adult; Humans; Antiviral Agents; Clobetasol; Herpes Labialis; Network Meta-Analysis; Valacyclovir
PubMed: 36914303
DOI: 10.1016/j.jebdp.2022.101778 -
Clinical Microbiology and Infection :... Aug 2020Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics. (Review)
Review
BACKGROUND
Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics.
AIMS
To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection.
SOURCES
PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions; Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015; MedRxiv for preprints within the last 12 months.
CONTENT
Study eligibility criteria were interventional and prospective observational studies (with or without a control group). Participants were adults and children with a confirmed viral infection. Interventions included the use of CQ or HCQ as antiviral agent in one or more groups of the study. Two authors independently screened abstracts, and all authors agreed on eligible studies. A meta-analysis was planned if studies were available which were similar in terms of participants, intervention, comparator and outcomes. Nineteen studies (including two preprints) were eligible (HIV 8, HCV 2, dengue 2, chikungunya 1, COVID-19 6). Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV are inconsistent. CQ is ineffective in curing dengue (high-certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure whether either CQ or HCQ has any benefit in clearing viraemia (very-low-certainty evidence).
IMPLICATIONS
Using HCQ or CQ for HIV/HCV infections is now clinically irrelevant as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue, and the same conclusion is likely for chikungunya. More evidence is needed to confirm whether either HCQ or CQ is beneficial in COVID-19 infection.
Topics: Adult; Antiviral Agents; Betacoronavirus; COVID-19; Child; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; Drug Repositioning; Humans; Hydroxychloroquine; Observational Studies as Topic; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Viral Load
PubMed: 32470568
DOI: 10.1016/j.cmi.2020.05.016 -
Fundamental & Clinical Pharmacology Apr 2021Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed... (Meta-Analysis)
Meta-Analysis Review
Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed mechanism is the inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importins, a necessary process for propagation of infections. We systematically reviewed the evidence for the applicability of ivermectin against viral infections including SARS-CoV-2 regarding efficacy, mechanisms and selective toxicity. The SARS-CoV-2 genome was mined to determine potential nuclear location signals for ivermectin and meta-analyses for in vivo studies included all comparators over time, dose range and viral replication in multiple organs. Ivermectin inhibited the replication of many viruses including those in Flaviviridae, Circoviridae and Coronaviridae families in vitro. Real and mock nuclear location signals were identified in SARS-CoV-2, a potential target for ivermectin and predicting a sequestration bait for importin β, stopping infected cells from reaching a virus-resistant state. While pharmacokinetic evaluations indicate that ivermectin could be toxic if applied based on in vitro studies, inhibition of viral replication in vivo was shown for Porcine circovirus in piglets and Suid herpesvirus in mice. Overall standardized mean differences and 95% confidence intervals for ivermectin versus controls were -4.43 (-5.81, -3.04), p < 0.00001. Based on current results, the potential for repurposing ivermectin as an antiviral agent is promising. However, further work is needed to reconcile in vitro studies with clinical efficacy. Developing ivermectin as an additional antiviral agent should be pursued with an emphasis on pre-clinical trials in validated models of infection.
Topics: Animals; Anthelmintics; Antiviral Agents; Computer Simulation; Drug Repositioning; Humans; Ivermectin; SARS-CoV-2; Swine; COVID-19 Drug Treatment
PubMed: 33427370
DOI: 10.1111/fcp.12644