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Current Pharmaceutical Biotechnology 2023Dengue fever is a disease with a high mortality rate around the world, which is an important issue for the health authorities of many countries. As a result of this, the... (Review)
Review
Dengue fever is a disease with a high mortality rate around the world, which is an important issue for the health authorities of many countries. As a result of this, the search for new drugs that are effective to combat this disease has become necessary. Medicinal plants have been used since ancient times to treat a wide list of diseases, including dengue fever. In this mini-review, 12 medicinal plants with known pharmacological properties are presented, which have been used in studies to evaluate their antiviral activity in vitro tests. Among the chemical agents involved in the antiviral response, found in the alcoholic extracts of these plants, are flavonoids, terpenes and alkaloids, which within the mechanism of action in blocking viral replication are considered entry inhibitors, fusion inhibitors, translation inhibitors and protease inhibitors. The present work shows whether these plants possess antiviral activity and the chemical compounds involved in this response.
Topics: Humans; Plants, Medicinal; Plant Extracts; Flavonoids; Antiviral Agents; Dengue
PubMed: 35619300
DOI: 10.2174/1389201023666220520110204 -
Clinical Pharmacokinetics Oct 2017Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the... (Review)
Review
Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the treatment of chronic HCV infection. Ombitasvir is predominantly metabolized by amide hydrolysis followed by oxidative metabolism and is a substrate of P-glycoprotein. Ombitasvir displays linear pharmacokinetics with minimal accumulation and is eliminated via metabolism and biliary excretion. A negligible amount of unchanged drug is excreted in urine. Exposures are comparable across Chinese, Japanese, and non-Asian subjects. The pharmacokinetic characteristics of ombitasvir are similar in healthy subjects and HCV-infected patients, and are not appreciably altered by hepatic or renal impairment. Results from several drug interaction studies demonstrated that ombitasvir has a low potential for drug interactions.
Topics: Anilides; Animals; Antiviral Agents; Carbamates; Drug Interactions; Drug Therapy, Combination; Food-Drug Interactions; Hepacivirus; Hepatitis C, Chronic; Humans; Proline; Valine
PubMed: 28229375
DOI: 10.1007/s40262-017-0518-4 -
Current Opinion in Virology Oct 2018The introduction of new multi-genotypic direct acting antivirals (DAA) in clinical practice has revolutionized HCV treatment, permitting the achievement of >95% rates of... (Review)
Review
The introduction of new multi-genotypic direct acting antivirals (DAA) in clinical practice has revolutionized HCV treatment, permitting the achievement of >95% rates of sustained virological response in many patients. However, virological failures can occur particularly if the treatments are sub optimal and/or with too short duration. Failure is often associated with development of resistance. The wide genetic variability in terms of different genotypes and subtypes, together with the natural presence and/or easy development of resistance during treatment, are intrinsic characteristics of HCV that may affect the treatment outcome and the chances of achieving a virological cure. This review explores in detail the aspects of HCV innate and treatment-induced resistance to new interferon-free DAA regimens.
Topics: Antiviral Agents; Drug Resistance, Multiple, Viral; Drug Therapy, Combination; Genetic Variation; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Ribavirin; Treatment Failure
PubMed: 30439589
DOI: 10.1016/j.coviro.2018.10.005 -
Trends in Pharmacological Sciences Nov 2018Viral diseases represent a major global problem in human health, with high morbidity and mortality. Despite recent progress in antiviral treatments, several viral... (Review)
Review
Viral diseases represent a major global problem in human health, with high morbidity and mortality. Despite recent progress in antiviral treatments, several viral diseases are still not controlled and millions suffer from them every year. It has recently emerged that purinergic signaling participates in viral infection and replication. Furthermore, stimulation of purinergic receptors in infected cells also induces inflammatory and antiviral responses, thus contributing to the host antiviral defense. Here we review the multiple roles played by the purinergic signaling network in cell-virus interactions that can lead either to viral maintenance in the cells or, by contrast, to stronger antiviral responses, and discuss potential future applications of purinergic signaling modulation for the treatment of viral diseases.
Topics: Animals; Antiviral Agents; Humans; Receptors, Purinergic; Signal Transduction; Virus Diseases
PubMed: 30292585
DOI: 10.1016/j.tips.2018.09.004 -
Frontiers in Immunology 2022The chronic infection with hepatitis B virus (HBV) is an important health problem that affects millions of people worldwide. Current therapies for HBV always suffer from... (Review)
Review
The chronic infection with hepatitis B virus (HBV) is an important health problem that affects millions of people worldwide. Current therapies for HBV always suffer from a poor response rate, common side effects, and the need for lifelong treatment. Novel therapeutic targets are expected. Interestingly, non-canonical structures of nucleic acids play crucial roles in the regulation of gene expression. Especially the formation of G-quadruplexes (G4s) in G-rich strands has been demonstrated to affect many bioprocesses including replication, transcription, and translation, showing great potential as targets in anticancer and antiviral therapies. In this review, we summarize recent antiviral studies about G4s and discuss the potential roles of G4 structures in antiviral therapy for HBV.
Topics: Humans; G-Quadruplexes; Hepatitis B virus; Antiviral Agents
PubMed: 36591216
DOI: 10.3389/fimmu.2022.1091873 -
Journal of Medical Virology Aug 2023Intrahepatic cholangiocyte organoids (ICOs) model was evaluated for host differences in hepatitis B virus (HBV) infection, cellular responses, antiviral, and...
Intrahepatic cholangiocyte organoids (ICOs) model was evaluated for host differences in hepatitis B virus (HBV) infection, cellular responses, antiviral, and immunomodulator responses. Twelve ICOs generated from liver resections and biopsies were assessed for metabolic markers and functional HBV entry receptor expression throughout differentiation. Structural changes relevant to HBV infection were characterized using histology, confocal, and electron microscopy examinations. Optimal ICO culture conditions for HBV infection using HepAD38 (genotype D) and plasma derived HBV (genotype B & C) were described. HBV infection was confirmed using HBcAg immunostaining, qRT-PCR (RNA, cccDNA, extracellular DNA), and ELISA (HBsAg and HBeAg). Drug response to antiviral and immunosuppressive agent, and cellular responses (interferon-stimulated genes [ISG]) to interferon-α and viral mimic (PolyI:C) were assessed. ICOs underwent metabolic and structural remodeling following differentiation. Optimal HBV infection was achieved in well-differentiated ICOs using spinoculation, with time and donor dependent increase in HBV RNA, cccDNA, extracellular DNA, HBeAg, and HBsAg. Donor dependent drug-responsiveness to entry inhibitor and JAK inhibitor was observed. Despite having a robust ISG response to interferon-α and PolyI:C, HBV infection in ICOs did not upregulate ISGs. Human ICOs support HBV infection and replication with donor dependent variation in viral dynamics and cellular responses. These features can be utilized for development of personalized drug testing platform for antivirals.
Topics: Humans; Hepatitis B virus; Hepatitis B Surface Antigens; Hepatitis B e Antigens; Hepatitis B, Chronic; Hepatitis B; Antiviral Agents; Interferon-alpha; Organoids; RNA; DNA, Viral; Liver
PubMed: 37503549
DOI: 10.1002/jmv.28975 -
Antiviral Research Sep 2023Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%....
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed individuals who lack robust immune responses following vaccination, and others at risk for severe COVID and long-COVID. RNA interference (RNAi) therapeutics induced by short interfering RNAs (siRNAs) offer a promising antiviral treatment option, with broad-spectrum antiviral capabilities unparalleled by current antiviral therapeutics and a high genetic barrier to antiviral escape. Here we describe novel siRNAs, targeting highly conserved regions of the SARS-CoV-1 and 2 genome of both human and animal species, with multi-variant antiviral potency against eight SARS-CoV-2 lineages - Ancestral VIC01, Alpha, Beta, Gamma, Delta, Zeta, Kappa and Omicron. Treatment with our siRNA resulted in significant protection against virus-mediated cell death in vitro, with >97% cell survival (P < 0.0001), and corresponding reductions of viral nucleocapsid RNA of up to 99.9% (P < 0.0001). When compared to antivirals; Sotrovimab and Remdesivir, the siRNAs demonstrated a more potent antiviral effect and similarly, when multiplexing siRNAs to target different viral regions simultaneously, an increased antiviral effect was observed compared to individual siRNA treatments (P < 0.0001). These results demonstrate the potential for a highly effective broad-spectrum direct acting antiviral against multiple SARS-CoV-2 variants, including variants resistant to antivirals and vaccine generated neutralizing antibodies.
Topics: Animals; Humans; RNA, Small Interfering; SARS-CoV-2; Antiviral Agents; Post-Acute COVID-19 Syndrome; COVID-19; Hepatitis C, Chronic; Antibodies, Neutralizing; Antibodies, Viral; Spike Glycoprotein, Coronavirus
PubMed: 37478918
DOI: 10.1016/j.antiviral.2023.105677 -
Journal of Gastroenterology May 2018Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is... (Review)
Review
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy. In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.
Topics: Antiviral Agents; Coinfection; Drug Therapy, Combination; HIV Infections; Hepatitis C; Humans; Immunocompromised Host; Interferons; Liver Transplantation; Postoperative Period; Protease Inhibitors; Recurrence; Renal Dialysis; Renal Insufficiency, Chronic; Ribavirin
PubMed: 29299684
DOI: 10.1007/s00535-017-1427-x -
Expert Opinion on Drug Metabolism &... 2015Neonatal patients, because of the inability of their immune system to properly respond to microbial challenge, are highly susceptible to viral infections.... (Review)
Review
INTRODUCTION
Neonatal patients, because of the inability of their immune system to properly respond to microbial challenge, are highly susceptible to viral infections. Immunoglobulins, monoclonal antibody and antiviral drugs are used for prophylaxis and treatment of viral diseases in neonates. Neonates and, especially, preterm infants differ in drug absorption, distribution, metabolism and excretion from adults and older children.
AREAS COVERED
This review will evaluate deficiencies of neonatal immune responses to microbial challenge that predispose newborns to viral infections, clinical manifestations and the treatment of viral diseases in neonates. We focus on published studies describing antiviral drug pharmacokinetics in neonates and make recommendations on the dosing of these drugs, allowing achievement of maximal clinical benefits in neonates.
EXPERT OPINION
While some efforts were undertaken to study pharmacokinetics and pharmacodynamics of antiviral drugs, much more needs to be done. Current data indicate that the pharmacokinetics of antiviral drugs may vary significantly depending on gestational age, maturation processes of drug-metabolizing enzymes and renal clearance. Specifics of pharmacokinetics of antiviral drugs need to be taken into consideration when they are prescribed to neonates and infants.
Topics: Adult; Age Factors; Animals; Antiviral Agents; Child; Disease Susceptibility; Dose-Response Relationship, Drug; Humans; Immune System; Infant, Newborn; Infant, Premature; Virus Diseases
PubMed: 26535960
DOI: 10.1517/17425255.2015.1108963 -
Emerging Microbes & Infections Dec 2023Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain-Barré syndrome in adults, and microcephaly in...
Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain-Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.
Topics: Infant, Newborn; Humans; Zika Virus; Transcriptome; Endothelial Cells; Zika Virus Infection; Antiviral Agents; Virus Replication
PubMed: 36715162
DOI: 10.1080/22221751.2023.2174777