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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 -
Journal of Clinical Medicine Jun 2023Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see... (Review)
Review
Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents (topical imiquimod 5% and 3.75% cream, sinecatechins 15% ointment) and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention.
PubMed: 37445264
DOI: 10.3390/jcm12134230 -
Drugs in Context 2018Penile warts are the most common sexually transmitted disease in males. Clinicians should be familiar with the proper evaluation and management of this common condition. (Review)
Review
BACKGROUND
Penile warts are the most common sexually transmitted disease in males. Clinicians should be familiar with the proper evaluation and management of this common condition.
OBJECTIVE
To provide an update on the current understanding, evaluation, and management of penile warts.
METHODS
A PubMed search was completed in Clinical Queries using the key terms 'penile warts' and 'genital warts'. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews.
RESULTS
Penile warts are caused by human papillomavirus (HPV), notably HPV-6 and HPV-11. Penile warts typically present as asymptomatic papules or plaques. Lesions may be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungating, or cauliflower-like. Approximately one-third of penile warts regress without treatment and the average duration prior to resolution is approximately 9 months. Active treatment is preferable to watchful observation to speed up clearance of the lesions and to assuage fears of transmission and autoinoculation. Patient-administered therapies include podofilox (0.5%) solution or gel, imiquimod 3.75 or 5% cream, and sinecatechins (polypheron E) 15% ointment. Clinician-administered therapies include podophyllin, cryotherapy, bichloroacetic or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy. Patients who do not respond to first-line treatments may respond to other therapies or a combination of treatment modalities. Second-line therapies include topical/intralesional/intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
CONCLUSION
No single treatment has been shown to be consistently superior to other treatment modalities. The choice of the treatment method should depend on the physician's comfort level with the various treatment options, the patient's preference and tolerability of treatment, and the number and severity of lesions. The comparative efficacy, ease of administration, adverse effects, cost, and availability of the treatment modality should also be taken into consideration.
PubMed: 30622585
DOI: 10.7573/dic.212563 -
Antioxidants (Basel, Switzerland) Jul 2022The term sinecatechins designates an extract containing a high percentage of catechins obtained from green tea, which is commercially registered as Veregen or Polyphenon...
Inhibition of Cell Proliferation and Cell Viability by Sinecatechins in Cutaneous SCC Cells Is Related to an Imbalance of ROS and Loss of Mitochondrial Membrane Potential.
The term sinecatechins designates an extract containing a high percentage of catechins obtained from green tea, which is commercially registered as Veregen or Polyphenon E (PE) and may be considered for treatment of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK). As shown here, treatment of four cSCC cell lines with 200 µg/mL of PE resulted in strong, dose-dependent decrease in cell proliferation (20-30%) as well as strongly decreased cell viability (4-21% of controls, 48 h). Effects correlated with loss of mitochondrial membrane potential, whereas early apoptosis was less pronounced. At the protein level, some activation of caspase-3 and enhanced expression of the CDK inhibitor p21 were found. Loss of MMP and induced cell death were, however, largely independent of caspases and of the proapoptotic Bcl-2 proteins Bax and Bak, suggesting that sinecatechins induce also non-apoptotic, alternative cell death pathways, in addition to apoptosis. Reactive oxygen species (ROS) were downregulated in response to PE at 4 h, followed by an increase at 24 h. The contributory role of initially reduced ROS was supported by the antioxidant N-acetyl cysteine, which in combination with PE further enhanced the negative effects on cell viability. Thus, sinecatechins inhibited cell proliferation and viability of cSCC cells, which could suggest the use of PE for AK treatment. The mechanisms appear as linked to an imbalance of ROS levels.
PubMed: 35883905
DOI: 10.3390/antiox11071416 -
Indian Dermatology Online Journal 2016Cutaneous and genital warts are common dermatological conditions caused by the human papilloma virus (HPV). Although it is a benign condition, it causes disfigurement,... (Review)
Review
Cutaneous and genital warts are common dermatological conditions caused by the human papilloma virus (HPV). Although it is a benign condition, it causes disfigurement, has a tendency to koebnerize, and can be transmitted to others. This makes adequate and timely treatment important. There are several conventional treatments available with variable response. Topical and systemic immunotherapy has now found a significant place in the treatment of warts because of its nondestructive action, ease of use, and promising results. Through this review, we would like to present a brief overview of the various immunotherapeutic agents used. These include more established agents such as imiquimod, vaccine, bacillus Calmette-Guérin vaccine, measles, mumps, and rubella vaccine, Candida antigen, trichophyton antigen, tuberculin, zinc, cimetidine, levamisole, HPV vaccine, and autoimplantation therapy. Other agents such as contact immunotherapy which is sparsely used now than before and newer agents such as , sinecatechins, echinacea, propolis, glycyrrizinic acid, and Vitamin D have also been discussed. The mechanism of action of these agents, along with their dosage, mode of administration, duration of use, expected outcomes and comparative efficacy, evidence for their use, and expected side effects, if any, are reviewed.
PubMed: 27730031
DOI: 10.4103/2229-5178.190487 -
The Journal of Clinical and Aesthetic... Feb 2012Green tea catechins possess a wide range of pharmacological properties, including antiviral, anti-infective, and immunostimulatory properties. They also have...
BACKGROUND
Green tea catechins possess a wide range of pharmacological properties, including antiviral, anti-infective, and immunostimulatory properties. They also have demonstrated inhibitory effects on a variety of enzymatic and metabolic pathways involved in cancer development. Catechins have been shown to have antiproliferative properties in various cell lines and may have direct virucidal effect. The United States Food and Drug Administration has approved a topical ointment formulation of sinecatechins, derived from green tea catechins and other tea components, for the treatment of external genital and perianal warts. The exact mechanism of action of sinecatechins in eradication of human papillomavirus-induced external genital and perianal warts is unknown, but may be due to one or more of the mechanisms mentioned.
OBJECTIVE
This study was conducted to investigate the growth inhibitory potential of the sinecatechins in human cervical carcinoma cell lines infected with human papillomavirus.
METHODS
The viability of tumor cell lines (CaSki and SiHa infected with human papillomavirus-16; HeLa and C4-I infected with human papillomavirus-18) was investigated as one parameter in a short-term viability assay (48 hours). This was followed by a long-term clonogenic assay (12-23 days) to determine the cytotoxic potential of sinecatechins as a parameter for cell viability and proliferation. This assay determined if the effect observed in the viability assay was due to retardation in cell proliferation or to a reduction of total cell number, leading to cell death.
RESULTS
Based on the data collected, sinecatechins inhibited cell growth in all four tumor cell lines by 50 percent (GI(50)) at concentrations ranging from 160 to 360µM. C4-I cells were the most sensitive to treatment with sinecatechins, with a lower GI(50) (~34µM). Total GI was achieved in a 48-hour assay at 625µM sinecatechins (40µM for C4-I), with growth inhibitory potential detectable after one hour. Clonogenic assays confirmed the cytotoxic potential of sinecatechins with a reduction in clone numbers in a concentration-dependent fashion. Sinecatechins substantially reduced the number of surviving HeLa cells at a concentration of 200µM, while surviving SiHa cells were almost totally eradicated with a concentration of 600µM.
CONCLUSION
Sinecatechins demonstrated growth inhibitory potential in all four human papillomavirus-infected tumor cell lines, which may be attributed to the induction of apoptosis, mediated by cell cycle deregulation. In addition, this antiproliferative effect may contribute to the overall cancer-preventative function and possible direct antiviral activity of sinecatechins that may contribute to external genital and perianal warts clearance.
PubMed: 22468171
DOI: No ID Found -
Journal of Medical Economics Mar 2010To evaluate the cost-effectiveness and treatment-cost impact of sinecatechins (Veregen) as first-line therapy against its principal comparator, imiquimod (Aldara), in... (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate the cost-effectiveness and treatment-cost impact of sinecatechins (Veregen) as first-line therapy against its principal comparator, imiquimod (Aldara), in the treatment of external genital warts (EGWs).
METHOD
A two-stage decision model is proposed to compare sinecatechins with its principal comparator, imiquimod, as a first-line topical therapy in the treatment of EGWs. The model utilizes estimates of sustained clearance from two pivotal sinecatechins trials and from a systematic literature review for imiquimod. Resource inputs are: (1) trial-based estimates of average drug utilization and (2) CPT (Current Procedural Terminology) codes describing anticipated office visits and utilization of second-line ablative procedures. The analysis considers: (1) comparative costs of achieving a successful outcome with sinecatechins versus imiquimod, and (2) comparative cost-consequences of sinecatechins versus imiquimod. As a modeled approach to evaluating comparative product effectiveness, the claims made reflect the structure of the model, which focuses on topical products as first-line therapy in EGW interventions and in its reliance on estimates of sustained clearance from pivotal randomized clinical trials (RCTs). Sustained clearance in this context being defined as the proportion of patients who report initial wart clearance over the RCT period corrected for subsequent recurrence.
RESULTS
As first-line therapy, sinecatechins dominates imiquimod as a lower cost treatment with a higher sustained clearance rate (51.9 vs. 40.6%). First-line average cost of treatment with sinecatechins is $774 compared to imiquimod at $930. Cost per successful outcome with sinecatechins is $1,492, which is lower than $2,289 for imiquimod. Taking account of patients failing first-line therapy moving to a second-line ablative therapy yields an average cost of treatment for patients initiated to sinecatechins of $943 and $1,138 for those initiated to imiquimod. A sensitivity assessment confirmed the position of sinecatechins within the decision-model framework.
CONCLUSION
Sinecatechins yields a lower cost of treatment compared to imiquimod in the treatment of EGW. It also offers cost savings to healthcare systems. This conclusion should be qualified by the limitations of the decision framework within which the assessment has been made. The model focuses on topical preparations as first-line therapies, with estimates of sustained clearance taken from pivotal RCTs. Treatment cost estimates are generated independently, but reflect current product and ancillary costs.
Topics: Aminoquinolines; Antineoplastic Agents; Camellia sinensis; Catechin; Condylomata Acuminata; Confidence Intervals; Cost-Benefit Analysis; Decision Support Techniques; Drug Utilization; Humans; Imiquimod; Models, Economic; Plant Extracts; Treatment Outcome; United States
PubMed: 19929627
DOI: 10.3111/13696990903451461 -
The Journal of Clinical and Aesthetic... Jan 2012Based on published studies, the biological properties of green tea catechins are antiviral, antioxidative, anticarcinogenic, antiangiogenic, and immunostimulatory. The...
BACKGROUND
Based on published studies, the biological properties of green tea catechins are antiviral, antioxidative, anticarcinogenic, antiangiogenic, and immunostimulatory. The United States Food and Drug Administration has approved a topical ointment formulation of sinecatechins, derived from green tea catechins and other tea components, for the treatment of external genital and perianal warts. The exact mechanism of action of sinecatechins in eradication of human papillomavirus-induced external genital and perianal warts is unknown, but may be due to one or more of the mechanisms mentioned.
OBJECTIVE
This study was conducted to investigate the effects of sinecatechins on proteases, inflammatory enzymes, and kinases contributing to human papillomavirus expression and growth.
DESIGN
Using commercially available in-vitro biochemical assays, sinecatechins were tested for their activity against matrix metalloproteinase (MMP-1, MMP-2, MMP-7, MMP-9); enzymes involved in oxidative stress (lipoxygenases and cyclooxygenases [COX-1, COX-2]); several growth factors (epidermal growth factor, platelet-derived growth factor, and transforming growth factor-β); and extracellular signal-regulated kinases 1/2. The ability of sinecatechins to inhibit ligand binding of growth factors was also studied.
RESULTS
Sinecatechins showed specific inhibition against a variety of enzymes at concentrations in the micromolar range. With the exception of matrix metalloproteinase-1, all proteases tested were inhibited in a dose-dependent manner. Pronounced inhibition of certain lipoxygenases was observed. Cyclooxygenases were also inhibited, with slight selectivity of greater inhibition against cyclooxygenases-2, the inducible form of cyclooxygenases. Extracellular signal-regulated kinases 1/2 (involved in human papillomavirus tumor cell growth) were also inhibited by sinecatechins at high concentrations, while epidermal growth factor receptor was inhibited at surprisingly low concentrations. In contrast, no inhibition of binding of various growth factors to their corresponding receptors was seen, highlighting the specificity of sinecatechins inhibitory activity. RESULTS demonstrated that sinecatechins specifically inhibit multiple human papillomavirus-induced pathways and molecules, likely contributing to external genital and perianal warts clearance via direct antiviral activity.
CONCLUSION
As expected, sinecatechins inhibited a broad range of enzymes and kinases involved in the generation of inflammatory mediators: proteases, oxygenases, and protein kinases were all inhibited by sinecatechins in the micromolar range.
PubMed: 22328955
DOI: No ID Found -
American Family Physician Sep 2014Genital warts affect 1% of the sexually active U.S. population and are commonly seen in primary care. Human papillomavirus types 6 and 11 are responsible for most...
Genital warts affect 1% of the sexually active U.S. population and are commonly seen in primary care. Human papillomavirus types 6 and 11 are responsible for most genital warts. Warts vary from small, flat-topped papules to large, cauliflower-like lesions on the anogenital mucosa and surrounding skin. Diagnosis is clinical, but atypical lesions should be confirmed by histology. Treatments may be applied by patients, or by a clinician in the office. Patient-applied treatments include topical imiquimod, podofilox, and sinecatechins, whereas clinician-applied treatments include podophyllin, bichloroacetic acid, and trichloroacetic acid. Surgical treatments include excision, cryotherapy, and electrosurgery. The quadrivalent human papillomavirus vaccine is active against virus subtypes that cause genital warts in men and women. Additionally, male circumcision may be effective in decreasing the transmission of human immunodeficiency virus, human papillomavirus, and herpes simplex virus.
Topics: Administration, Topical; Adult; Antineoplastic Agents; Combined Modality Therapy; Condylomata Acuminata; Cryotherapy; Diagnosis, Differential; Electrosurgery; Female; Human papillomavirus 11; Humans; Keratolytic Agents; Male; Papillomavirus Infections; Papillomavirus Vaccines; Precancerous Conditions; Urogenital Surgical Procedures
PubMed: 25251091
DOI: No ID Found