-
Clinical Microbiology Reviews Jul 2016Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment... (Review)
Review
Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.
Topics: Antiviral Agents; Communicable Diseases; Drug Approval; Drug Discovery; Humans
PubMed: 27281742
DOI: 10.1128/CMR.00102-15 -
BMJ Clinical Evidence Oct 2010Although there is some variability (depending on the definition of postherpetic neuralgia), about 10% of those with zoster will have persisting pain 1 month after the... (Review)
Review
INTRODUCTION
Although there is some variability (depending on the definition of postherpetic neuralgia), about 10% of those with zoster will have persisting pain 1 month after the rash.The main risk factor for postherpetic neuralgia is increasing age; it is uncommon in people aged <50 years, but develops in 20% of people aged 60 to 65 years who have had acute herpes zoster, and in >30% of those people aged >80 years. Up to 2% of people with acute herpes zoster may continue to have postherpetic pain for 5 years or more.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions aimed at preventing herpes zoster and subsequent postherpetic neuralgia? What are the effects of interventions during an acute attack of herpes zoster aimed at preventing postherpetic neuralgia? What are the effects of interventions to relieve established postherpetic neuralgia after the rash has healed? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 41 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, capsaicin, dextromethorphan, dressings, gabapentin, herpes zoster vaccine, oral antiviral agents, oral opioid analgesics, lidocaine, topical antiviral agents (idoxuridine), and tricyclic antidepressants.
Topics: Antidepressive Agents, Tricyclic; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Neuralgia, Postherpetic
PubMed: 21418680
DOI: No ID Found -
Antiviral Chemistry & Chemotherapy Jan 2013This review article focuses on the anti-herpesvirus agents effective against herpes simplex virus, varicella-zoster virus and cytomegalovirus, which have either been... (Review)
Review
This review article focuses on the anti-herpesvirus agents effective against herpes simplex virus, varicella-zoster virus and cytomegalovirus, which have either been licensed for clinical use (idoxuridine, trifluridine, brivudin, acyclovir, valaciclovir, valganciclovir, famciclovir and foscarnet) or are under clinical development (CMX001 [the hexadecyloxypropyl prodrug of cidofovir], the helicase-primase inhibitor BAY 57-1293 [now referred to as AIC316], FV-100 [the valine ester of Cf 1743] and the terminase inhibitor letermovir [AIC246]).
Topics: Animals; Antiviral Agents; Cytomegalovirus; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Simplexvirus
PubMed: 23343513
DOI: 10.3851/IMP2533 -
Science (New York, N.Y.) Aug 2021Stochastic fluctuations in gene expression ("noise") are often considered detrimental, but fluctuations can also be exploited for benefit (e.g., dither). We show here...
Stochastic fluctuations in gene expression ("noise") are often considered detrimental, but fluctuations can also be exploited for benefit (e.g., dither). We show here that DNA base excision repair amplifies transcriptional noise to facilitate cellular reprogramming. Specifically, the DNA repair protein Apex1, which recognizes both naturally occurring and unnatural base modifications, amplifies expression noise while homeostatically maintaining mean expression levels. This amplified expression noise originates from shorter-duration, higher-intensity transcriptional bursts generated by Apex1-mediated DNA supercoiling. The remodeling of DNA topology first impedes and then accelerates transcription to maintain mean levels. This mechanism, which we refer to as "discordant transcription through repair" ("DiThR," which is pronounced "dither"), potentiates cellular reprogramming and differentiation. Our study reveals a potential functional role for transcriptional fluctuations mediated by DNA base modifications in embryonic development and disease.
Topics: Animals; Cell Differentiation; Cells, Cultured; Cellular Reprogramming; Computer Simulation; DNA; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase; Embryonic Stem Cells; Gene Expression; Idoxuridine; Mice; Models, Genetic; Nanog Homeobox Protein; Nucleic Acid Conformation; RNA, Messenger; Single-Cell Analysis; Stochastic Processes; Thymidine Kinase; Transcription, Genetic
PubMed: 34301855
DOI: 10.1126/science.abc6506 -
BMC Ophthalmology Apr 2015This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types.
DATA SOURCES
Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) "Keratitis, Herpetic/" AND "Acyclovir/" limiting by the key words "topical" OR "ointment" and also restricted to MESH "Administration, Topical/" OR "Ointments/". The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1-134, 2009 and GlaxoSmithKline clinical documents related to acyclovir.
STUDY SELECTION
Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven.
DATA EXTRACTION
Data independently extracted from identified articles by two authors of this manuscript.
DATA SYNTHESIS
Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9. Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact.
RESULTS
ACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p < 0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p = 0.0244).
CONCLUSION
ACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.
Topics: Acyclovir; Antiviral Agents; Follow-Up Studies; Humans; Idoxuridine; Keratitis, Herpetic; Ointments; Time Factors; Treatment Outcome
PubMed: 25928630
DOI: 10.1186/s12886-015-0022-2 -
The Cochrane Database of Systematic... Dec 2010Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis.
OBJECTIVES
To compare the relative effectiveness of antiviral agents, interferon, and corneal débridement in the treatment of acute HSV epithelial keratitis.
SEARCH STRATEGY
We searched CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (January 1950 to October 2010), EMBASE (January 1980 to October 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2010), Zetoc (British Library's Electronic Table of Contents), System for Information on Grey Literature in Europe (openSIGLE), Biosciences Information Service (BIOSIS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), Japan Information Center of Science and Technology (JICST-EPlus), and China Academic Journals database (CAJ) via China National Knowledge Infrastructure (CNKI) with citations confirmed using China/Asia On Demand (COAD). There were no language or date restrictions in the search for trials. All databases except CNKI and COAD were last searched on 27 October 2010, CNKI and COAD were searched on 1 April 2010. We also searched literature digests, conference proceedings and reference lists.
SELECTION CRITERIA
Of 152 eligible studies,106 comparative treatment trials involving 5872 eyes with dendritic or geographic epithelial keratitis were analysed for corneal healing over two weeks.
DATA COLLECTION AND ANALYSIS
Interventions were compared at 14 days after trial enrolment by calculating a risk ratio (RR) that was adjusted with indirect RR, assessed by an inconsistency index (I(2) ) and supplemented by a seven-day RR and a hazard ratio (HR).
MAIN RESULTS
Idoxuridine, though uncertainly better in healing outcome than control because of few trials with 14-day follow up, allowed earlier corneal re-epithelialisation. Vidarabine resulted in a significantly better outcome than placebo in one trial (RR 1.96; 95% CI 1.10 to 3.49). Compared to idoxuridine, in combined direct and indirect analyses, vidarabine (RR 1.11; 95% CI 1.03 to 1.19), trifluridine (RR 1.31; 95% CI 1.20 to 1.42), acyclovir (RR 1.23; 95% CI 1.16 to 1.31), brivudine (RR 1.38; 95% CI 1.18 to 1.61), and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) were significantly more effective. Trifluridine (RR 1.12; 95% CI 1.04 to 1.21) and acyclovir (RR 1.11; 95% CI 1.05 to 1.19) appeared more effective than vidarabine. No significant differences were found in comparisons between acyclovir, trifluridine and brivudine. The comparison of ganciclovir to acyclovir was limited by heterogeneity and possible publication bias. The joint use of two topical antivirals (RR 1.00; 95% CI 0.89 to 1.12) and the use of oral acyclovir alone (RR 0.92; 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.08; 95% CI 0.99 to 1.17) appeared as effective as topical antiviral therapy. Compared to antiviral monotherapy, the combination of an antiviral with interferon (RR 1.03; 95% CI 0.99 to 1.07) or with débridement (RR 1.04; 95% CI 0.95 to 1.14) did not yield significantly better outcomes but may have accelerated healing. The corneal epithelial healing outcome was improved when antiviral therapy was added to débridement (RR 1.21; 95% CI 1.04 to 1.42).
AUTHORS' CONCLUSIONS
Trifluridine and acyclovir are more effective than idoxuridine or vidarabine, and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Debridement; Humans; Interferons; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 21154352
DOI: 10.1002/14651858.CD002898.pub4 -
British Medical Journal Aug 1968
Topics: Acute Disease; Adolescent; Adult; Aged; Central Nervous System; Child; Child, Preschool; Complement Fixation Tests; Encephalitis; Humans; Idoxuridine; Infant; Infant, Newborn; Meningitis; Microscopy, Electron; Middle Aged; Necrosis; Neutralization Tests; Simplexvirus
PubMed: 4298666
DOI: No ID Found -
British Medical Journal Apr 1972
Topics: Animals; Cytarabine; Dexamethasone; Encephalitis; Herpes Simplex; Humans; Idoxuridine; Intracranial Pressure
PubMed: 5022732
DOI: 10.1136/bmj.2.5807.226-b -
Journal of Molecular Structure Nov 2021Two thiazole-based complexes were prepared from Co(II) and Cu(II) ions. The new ligand and its complexes were fully characterized by analytical and spectral techniques....
Synthesis and characterization of new thiazole-based Co(II) and Cu(II) complexes; therapeutic function of thiazole towards COVID-19 in comparing to current antivirals in treatment protocol.
Two thiazole-based complexes were prepared from Co(II) and Cu(II) ions. The new ligand and its complexes were fully characterized by analytical and spectral techniques. The ligand behaved as a neutral tridentate in its keto-form towards the metals O(8), O(10) and O(18) atoms. This was suggested based on the lower shift of υ(CH[bond, double bond]O), υ(C[bond, double bond]O) and υ(C-O) vibrations. The electronic transitions in Co(II)-HL and Cu(II)-HL complexes displayed - transitions which belong to T→A(F) & T(F)→T (P) and Eg →Tg, in the two complexes, respectively. ESR spectrum of Cu(II)-HL complex displayed g-factor by the following order; g(2.1740)>g(2.0935)>2.0023, which agrees with octahedral geometry. The geometry optimization was executed by DFT/B3LYP method under valence double zeta polarized basis set (6-31G*), to confirm the structural forms and the mode of bonding. The orientation and the charges of O(8), O(10) and O(18) atoms, support the coordination of the ligand in its keto-form with the metal ions. Pharmacophore profiles were obtained regarding thiazole ligand and other recommended drugs (arbidol, avigan and idoxuridine) that used in treatment protocol of COVID-19 pandemic. Also, query was run in MolPort-library to obtain antiviral analogues, to broaden the search for an effective treatment. Three analogues were obtained for arbidol, avigan and idoxuridine drugs, which have the following numbers; MolPort-047-605-644, MolPort-004-768-508 and MolPort-028-750-709, respectively. Moreover, molecular docking was carried out to obtain all interaction details and rank the efficiency of thiazole compound versus the three antivirals in their interaction with the two COVID-19 proteins. The outcomes suggested the significant antiviral activity of idoxuridine and thiazole (enol-form), which not reach to eliminate the pandemic exactly. While, arbidol and avigan did not have an effective antiviral role, although they still used in COVID-19 treatment protocol.
PubMed: 34188314
DOI: 10.1016/j.molstruc.2021.130961 -
The Cochrane Database of Systematic... Aug 2016Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode.
OBJECTIVES
To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (from inception to April 2016), MEDLINE (from inception to April 2016), the Specialised Register of the Cochrane Sexually Transmitted Infections Review Group (from inception to April 2016), EMBASE (from inception to April 2016), PsycINFO (from inception to April 2016), CINAHL (from inception to April 2016), LILACS (from inception to April 2016), AMED (from inception to April 2016), and the Alternative Medicines Specialised Register (from inception to April 2016). We handsearched a number of relevant journals, searched reference lists of all included studies, databases of ongoing trials, and other Internet databases.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) on participants with first-episode genital herpes. We excluded vaccination trials, and trials in which the primary objective assessed a complication of HSV infection.
DATA COLLECTION AND ANALYSIS
All studies written in English were independently assessed by at least two review authors for inclusion, risk of bias for each trial, and to extract data. Studies requiring translation were assessed for inclusion, trial quality, and data extraction by external translators.
MAIN RESULTS
We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials. This review found low quality evidence from two studies of oral acyclovir, when compared to placebo, reduced the duration of symptoms in individuals undergoing their first episode of genital herpes (mean difference (MD) -3.22, 95% confidence interval (CI) -5.91 to -0.54; I(2) = 52%). In two studies (112 participants), intravenous acyclovir decreased the median number of days that patients with first-episode herpes suffered symptoms. Oral valaciclovir (converted to acyclovir) also showed a similar length of symptom duration when compared to acyclovir in two studies.There is currently no evidence that topical acyclovir reduces symptoms (MD -0.61 days, 95% CI -2.16 to 0.95; 3 RCTs, 195 participants, I(2) statistic = 56%). There is also no current evidence that the topical treatments of cicloxolone cream, carbenoxolone sodium cream, adenosine arabinoside, idoxuridine in dimethyl sulfoxide, when compared to placebo reduced the duration of symptoms in people undergoing their first episode of herpes.Two studies reported no evidence of a reduction in the number of median days to recurrence following treatment with oral acyclovir versus placebo. Adverse events were generally poorly reported by all of the included studies and we were unable to quantitatively analyse this outcome. For those taking acyclovir, there were no serious adverse events; the most common adverse events reported for oral acyclovir were coryza, dizziness, tiredness, diarrhoea and renal colic. For intravenous acyclovir these were phlebitis, nausea and abnormal liver function tests and for topical acyclovir there was pain with the topical application.Those undergoing interferon treatment had significantly more adverse events compared to those taking placebo.
AUTHORS' CONCLUSIONS
There is low quality evidence from this review that oral acyclovir reduced the duration of symptoms for genital herpes. However, there is low quality evidence which did not show that topical antivirals reduced symptom duration for patients undergoing their first episode of genital herpes. This review was limited by the inclusion of skewed data, resulting in few trials that we were able to meta-analyse.
Topics: Acyclovir; Administration, Oral; Antiviral Agents; Female; Herpes Genitalis; Humans; Injections, Intravenous; Male; Randomized Controlled Trials as Topic; Recurrence; Valacyclovir; Valine
PubMed: 27575957
DOI: 10.1002/14651858.CD010684.pub2