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Infectious Diseases of Poverty Mar 2019At present, there is a continuous flow of immigrants from the south of the world to north-western countries. Often immigrants originate from areas of high-prevalence of... (Review)
Review
BACKGROUND
At present, there is a continuous flow of immigrants from the south of the world to north-western countries. Often immigrants originate from areas of high-prevalence of viral hepatitis and pose a challenge to the healthcare systems of the host nations. Aims of this study is to evaluate the prevalence and virological and clinical characteristics of hepatitis C virus (HCV) infection in immigrants and the strategies to identify and take care of the immigrants infected with HCV.
MAIN BODY
We conducted an electronic literature search in several biomedical databases, including PubMed, Google Scholar, Scopus, Web of Science, using different combinations of key words: "HCV infection; chronic hepatitis C, immigrants; low-income countries". We included studies written in English indicating the epidemiological data of HCV infection in the immigrant population, studies that assessed the clinical presentation, clinical management and treatment with directly acting antiviral agent in immigrants, HCV infection is unevenly distributed in different countries, with worldwide prevalence in the general population ranging from 0.5 to 6.5%. In Western countries and Australia this rate ranges from 0.5 to 1.5%, and reaches 2.3% in countries of south-east Asia and eastern Mediterranean regions, 3.2% in China, 0.9% in India, 2.2% in Indonesia and 6.5% in Pakistan; in sub-Saharan Africa the prevalence of HCV infection varies from 4 to 9%. Immigrants and refugees from intermediate/high HCV endemic countries to less- or non-endemic areas are more likely to have an increased risk of HCV infection due to HCV exposure in their countries of origin. Because of the high HCV endemicity in immigrant populations and of the high efficacy of directly acting antiviral agent therapy, a campaign could be undertaken to eradicate the infection in this setting.
CONCLUSIONS
The healthcare authorities should support screening programs for immigrants, performed with the help of cultural mediators and including educational aspects to break down the barriers limiting access to treatments, which obtain the HCV clearance in 95% of cases and frequently prevent the development of liver cirrhosis and hepatocellular carcinoma.
Topics: Antiviral Agents; Emigrants and Immigrants; Genotype; Global Health; Hepacivirus; Hepatitis C; Humans; Risk Factors; World Health Organization
PubMed: 30871599
DOI: 10.1186/s40249-019-0528-6 -
Molecules (Basel, Switzerland) Oct 2022A series of oxazinyl flavonoids were synthesized on the basis of flavone. The structures of all target compounds were characterized by H NMR, C NMR, and HRMS. The effect...
A series of oxazinyl flavonoids were synthesized on the basis of flavone. The structures of all target compounds were characterized by H NMR, C NMR, and HRMS. The effect of the different substituent on the N-position of oxazinyl flavonoids against tobacco mosaic virus (TMV) activities and plant pathogen activities was systematically investigated. In vivo anti-TMV activity showed that most of the compounds showed moderate-to-excellent antiviral activities against TMV at 500 μg/mL. Compounds , , -, and - showed better antiviral activities than ribavirin (a commercially available antiviral agent) and apigenin. In particular, compounds and even displayed slightly higher activities than ningnanmycin, which were expected to become new antiviral candidates. Antiviral mechanism research by molecular docking exhibited that compounds and could interact with TMV CP and inhibit virus assembly. Then, the antifungal activities of these compounds against six kinds of plant pathogenic fungi were tested, and the results showed that these oxazinyl flavonoids had broad-spectrum fungicidal activities. Compounds exhibited antifungal activity of up to 91% against and might become a candidate drug for new fungicides.
Topics: Antiviral Agents; Ribavirin; Fungicides, Industrial; Antifungal Agents; Structure-Activity Relationship; Flavonoids; Molecular Docking Simulation; Apigenin; Molecular Structure; Alkaloids; Tobacco Mosaic Virus; Fungi; Drug Design
PubMed: 36296469
DOI: 10.3390/molecules27206875 -
Future Medicinal Chemistry May 2022In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human...
In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.
Topics: Antiviral Agents; Drug Repositioning; Dyphylline; Humans; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35387498
DOI: 10.4155/fmc-2021-0311 -
Expert Opinion on Pharmacotherapy Dec 2022The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with...
INTRODUCTION
The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with SARS-CoV-2 can trigger a hyperinflammatory response of both the adaptive and innate immune system that has been associated with severe disease, hospitalization, and death, and better treatment options are urgently needed.
AREAS COVERED
A mainstay of therapy for COVID-19 involves an antiviral agent, remdesivir, in combination with a systemic corticosteroid, dexamethasone.
EXPERT OPINION
The addition of a second immunomodulator, such as an interleukin-6 inhibitor or a Janus kinase inhibitor, has been associated with clinical benefit in a subset of patients with moderate-to-severe disease, but their use remains controversial. This manuscript reviews what is known about the approach to treatment of severe COVID-19 and examines how immunomodulators such as infliximab and abatacept may alter clinical management and COVID-19 research in the years ahead based on the results of randomized, controlled trials.
Topics: Humans; SARS-CoV-2; Antiviral Agents; Hospitalization; COVID-19 Drug Treatment
PubMed: 36271630
DOI: 10.1080/14656566.2022.2140041 -
Nature Reviews. Gastroenterology &... Aug 2015Mathematically modelling changes in HCV RNA levels measured in patients who receive antiviral therapy has yielded many insights into the pathogenesis and effects of... (Review)
Review
Mathematically modelling changes in HCV RNA levels measured in patients who receive antiviral therapy has yielded many insights into the pathogenesis and effects of treatment on the virus. By determining how rapidly HCV is cleared when viral replication is interrupted by a therapy, one can deduce how rapidly the virus is produced in patients before treatment. This knowledge, coupled with estimates of the HCV mutation rate, enables one to estimate the frequency with which drug resistant variants arise. Modelling HCV also permits the deduction of the effectiveness of an antiviral agent at blocking HCV replication from the magnitude of the initial viral decline. One can also estimate the lifespan of an HCV-infected cell from the slope of the subsequent viral decline and determine the duration of therapy needed to cure infection. The original understanding of HCV RNA decline under interferon-based therapies obtained by modelling needed to be revised in order to interpret the HCV RNA decline kinetics seen when using direct-acting antiviral agents (DAAs). There also exist unresolved issues involving understanding therapies with combinations of DAAs, such as the presence of detectable HCV RNA at the end of therapy in patients who nonetheless have a sustained virologic response.
Topics: Antiviral Agents; Biomarkers; Drug Resistance, Viral; Drug Therapy, Combination; Hepatitis C, Chronic; Humans; Interferon-alpha; Liver Regeneration; Models, Biological; RNA, Viral; Time Factors; Treatment Outcome; Viral Load; Virion
PubMed: 26122475
DOI: 10.1038/nrgastro.2015.97 -
Indian Journal of Public Health Jun 2020A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan,... (Review)
Review
A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.
Topics: Antimalarials; Antiviral Agents; Betacoronavirus; COVID-19; Clinical Trials as Topic; Coronavirus; Coronavirus Infections; Humans; Immunization, Passive; Immunoglobulins; Interleukins; Pandemics; Pneumonia, Viral; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 32496239
DOI: 10.4103/ijph.IJPH_456_20 -
Antiviral Research Oct 2014Originally developed and commercialized as an antiprotozoal agent, nitazoxanide was later identified as a first-in-class broad-spectrum antiviral drug and has been... (Review)
Review
Originally developed and commercialized as an antiprotozoal agent, nitazoxanide was later identified as a first-in-class broad-spectrum antiviral drug and has been repurposed for the treatment of influenza. A Phase 2b/3 clinical trial recently published in The Lancet Infectious Diseases found that oral administration of nitazoxanide 600mg twice daily for five days reduced the duration of clinical symptoms and reduced viral shedding compared to placebo in persons with laboratory-confirmed influenza. The same study also suggested a potential benefit for subjects with influenza-like illness who did not have influenza or other documented respiratory viral infection. From a chemical perspective, nitazoxanide is the scaffold for a new class of drugs called thiazolides. These small-molecule drugs target host-regulated processes involved in viral replication. Nitazoxanide is orally bioavailable and safe with extensive post-marketing experience involving more than 75 million adults and children. A new dosage formulation of nitazoxanide is presently undergoing global Phase 3 clinical development for the treatment of influenza. Nitazoxanide inhibits a broad range of influenza A and B viruses including influenza A(pH1N1) and the avian A(H7N9) as well as viruses that are resistant to neuraminidase inhibitors. It is synergistic with neuraminidase inhibitors, and combination therapy with oseltamivir is being studied in humans as part of ongoing Phase 3 clinical development. Nitazoxanide also inhibits the replication of a broad range of other RNA and DNA viruses including respiratory syncytial virus, parainfluenza, coronavirus, rotavirus, norovirus, hepatitis B, hepatitis C, dengue, yellow fever, Japanese encephalitis virus and human immunodeficiency virus in cell culture assays. Clinical trials have indicated a potential role for thiazolides in treating rotavirus and norovirus gastroenteritis and chronic hepatitis B and chronic hepatitis C. Ongoing and future clinical development is focused on viral respiratory infections, viral gastroenteritis and emerging infections such as dengue fever.
Topics: Antiparasitic Agents; Antiviral Agents; DNA Virus Infections; Drug Repositioning; Humans; Influenza, Human; Nitro Compounds; Thiazoles; Virus Replication
PubMed: 25108173
DOI: 10.1016/j.antiviral.2014.07.014 -
Current Allergy and Asthma Reports Jan 2021Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy... (Review)
Review
PURPOSE OF REVIEW
Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy against the novel SARS-CoV-2 virus. This review describes the history, mechanisms, pharmacokinetics, therapeutic applications, and safety profile of hydroxychloroquine as an immunomodulatory and antiviral agent. It also summarizes the major studies that launched and assessed the use of hydroxychloroquine against COVID-19 infection.
RECENT FINDINGS
More recent literature calls into question the long-held dogma that endolysosomal alkalinization is the primary mode of action of hydroxychloroquine. Ongoing uncertainty about the multiple potential mechanisms contributing to the therapeutic effect of hydroxychloroquine in rheumatic and viral disease led to a natural avenue for exploration in the treatment of COVID-19. Taken as a whole, the literature does not support utilizing hydroxychloroquine to treat or prevent infection from the SARS-CoV-2 virus. This is, at least in part, due to the wide variability in hydroxychloroquine pharmacokinetics between patients and difficulty achieving adequate target tissue concentrations of hydroxychloroquine without encountering unacceptable toxicities. Hydroxychloroquine continues to be a routinely prescribed, well-tolerated, effective, and low-cost treatment for rheumatic disease. Its therapeutic versatility has led to frequent repurposing for other conditions, most recently as an investigative treatment against the SARS-CoV-2 virus. Despite overall negative findings, the intense study of hydroxychloroquine against COVID-19 infection has enhanced our overall understanding of how hydroxychloroquine operates in autoimmune disease and beyond.
Topics: Animals; Antiviral Agents; Humans; Hydroxychloroquine; Rheumatologists; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33475900
DOI: 10.1007/s11882-020-00983-9 -
Otology & Neurotology : Official... Aug 2022Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates...
OBJECTIVE
Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates among patients receiving a normal-dose corticosteroid (prednisolone [PSL] 60 mg/d) or high-dose corticosteroid (PSL 200 mg/d), both with or without an antiviral agents. Recovery rates were also examined based on the order of presentation of herpetic vesicles versus facial palsy.
STUDY DESIGN
Retrospective case review.
SETTING
Tertiary referral center.
PATIENTS
A total of 128 patients with HB grade VI RHS were treated in our department between 1995 and 2017. These patients were divided into four treatment groups based on corticosteroid dosage and use of an antiviral agent.
METHODS
We assessed treatment outcomes for HB grade VI patients together with logistic regression analysis to investigate factors that can impact treatment outcomes, that is, sex, age, days to start of treatment, PSL dosage, and antiviral agent administration.
RESULTS
Recovery rates were best in the high-dose corticosteroid group with an antiviral agent (71.1%) in comparison with the normal-dose corticosteroid group with an antiviral agent (60.0%) or high-dose corticosteroid alone (57.1%). Significant factors for treatment outcomes were high-dose corticosteroid administration and early initiation of treatment. A better recovery rate was also found when the herpetic vesicles appeared before facial palsy.
CONCLUSION
We showed that a combination of a high-dose corticosteroid and antiviral agent produced the best outcomes for patients with HB grade VI RHS. However, our results were not statistically significant because of small sample size.
Topics: Adrenal Cortex Hormones; Antiviral Agents; Bell Palsy; Facial Paralysis; Herpes Zoster Oticus; Humans; Myoclonic Cerebellar Dyssynergia; Prednisolone; Retrospective Studies
PubMed: 35878642
DOI: 10.1097/MAO.0000000000003582 -
International Journal of Molecular... Oct 2022In this research, the synergistic antiviral effects of carbon nanotubes (CNTs) and metal oxides (MO) in the form of novel hybrid structures (MO-CNTs) are presented. Raw...
In this research, the synergistic antiviral effects of carbon nanotubes (CNTs) and metal oxides (MO) in the form of novel hybrid structures (MO-CNTs) are presented. Raw CNTs, Ni(OH), FeO and MnO, as well as Ni(OH)-CNT, FeO-CNT and MnO-CNT were explored in this study against MS2 bacteriophage, which was used as a virus surrogate. The nano particles were synthesized and characterized using field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), particle size analysis, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Kinetic parameters such as the LD (lethal dose to kill 50% of the population), T and T (time taken to kill 50% and 80% of the population), SGR (specific growth rate) and IRD (initial rate of deactivation of the population) were also studied to examine the antiviral efficacy of these nanomaterials. Among all the nanomaterials, Ni(OH)-CNT was the most effective antiviral agent followed by FeO-CNT, MnO-CNT, raw CNTs, Ni(OH), FeO and MnO. When comparing the metal oxide-CNTs to the raw CNTs, the average enhancement was 20.2%. The average antiviral activity enhancement of the MO-CNTs were between 50 and 54% higher than the MO itself. When compared to the raw CNTs, the average enhancement over all the MO-CNTs was 20.2%. The kinetic studies showed that the LD of Ni(OH)-CNT was the lowest (16µg/mL), which implies that it was the most toxic of all the compounds studied. The LD of Ni(OH), FeO and MnO were 17.3×, 14.5× and 10.8× times greater than their corresponding hybrids with the CNTs. The synergistic mechanism involved the entrapment of phage viruses by the nano structured CNTs leading to structural damage along with toxicity to phage from the release of MO ions. The metal oxide-CNT nano hybrids developed in this project are promising candidates in applications such as antiviral coatings, nanocomposites, adsorbents and as components of personal protection gears.
Topics: Antiviral Agents; Kinetics; Manganese Compounds; Nanotubes, Carbon; Oxides
PubMed: 36233260
DOI: 10.3390/ijms231911957