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Antiviral Chemistry & Chemotherapy 2018
Topics: Antiviral Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Nucleosides; Prodrugs; Structure-Activity Relationship; Viruses
PubMed: 29890841
DOI: 10.1177/2040206618781410 -
Current Opinion in Virology Feb 2022To establish successful infection in cells, it is essential for hepatitis C virus (HCV) to overcome intracellular antiviral responses. The host cell mechanism that... (Review)
Review
To establish successful infection in cells, it is essential for hepatitis C virus (HCV) to overcome intracellular antiviral responses. The host cell mechanism that fights against the virus culminates in the production of interferons (IFNs), IFN-stimulated genes (ISGs) and pro-inflammatory cytokines as well as the induction of autophagy and apoptosis. HCV has developed multiple means to disrupt the host signaling pathways that lead to these antiviral responses. HCV impedes signaling pathways initiated by pattern-recognition receptors (PRRs), usurps and uses the antiviral autophagic response to enhance its replication, alters mitochondrial dynamics and metabolism to prevent cell death and attenuate IFN response, and dysregulates inflammasomal response to cause IFN resistance and immune tolerance. These effects of HCV allow HCV to successful replicate and persist in its host cells.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Humans; Immunity, Innate; Interferons; Virus Replication
PubMed: 34973476
DOI: 10.1016/j.coviro.2021.12.010 -
Current Opinion in Virology Dec 2023An estimated 257 million people are chronic carriers of hepatitis-B virus (HBV) infection, which resulted in around 1 million deaths, mainly due to hepatocellular... (Review)
Review
An estimated 257 million people are chronic carriers of hepatitis-B virus (HBV) infection, which resulted in around 1 million deaths, mainly due to hepatocellular carcinoma (HCC). Long-term nucleotide analog treatment of HBV infection is associated with favorable prognosis, no disease progression, and a reduction of HCC risk, but lifelong treatments are required. A better understanding of HBV replication cycle and the host immune response will likely improve the identification of new targets for drug development. Studies are ongoing to determine if it is possible to successfully combine direct-acting antivirals (DAA) with an immunomodulatory therapy to allow increased cure rates. This review will start with summarizing the HBV replication cycle, recall current treatments, and then discuss potential targets and antiviral approaches in development to optimistically reach the HBV cure.
Topics: Humans; Hepatitis B virus; Antiviral Agents; Herpesvirus 1, Cercopithecine; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis C, Chronic; Virus Replication
PubMed: 37696687
DOI: 10.1016/j.coviro.2023.101360 -
Drug Discovery Today Jul 2022For emerging and re-emerging epidemic infections, researchers face challenges to develop broad-spectrum antivirals as well as reducing development time and costs, and... (Review)
Review
For emerging and re-emerging epidemic infections, researchers face challenges to develop broad-spectrum antivirals as well as reducing development time and costs, and drug resistance. Drug repurposing is a reliable strategy for rapidly discovering potent new antiviral agents, reducing the need for clinical trials. In this review, we outline antiviral drug candidates identified using the drug repurposing approach, with their potential modes of action and biological responses against various epidemic viral infectious diseases.
Topics: Antiviral Agents; Drug Repositioning; Epidemics; Viruses
PubMed: 35427764
DOI: 10.1016/j.drudis.2022.04.008 -
Nature Reviews. Microbiology Jul 2024The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality,... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.
Topics: Humans; Antiviral Agents; COVID-19 Drug Treatment; Drug Discovery; SARS-CoV-2; COVID-19; Animals
PubMed: 38622352
DOI: 10.1038/s41579-024-01036-y -
Frontiers in Immunology 2022Emergence of new, pandemic-level viral threats has brought to the forefront the importance of viral immunology and continued improvement of antiviral therapies.... (Review)
Review
Emergence of new, pandemic-level viral threats has brought to the forefront the importance of viral immunology and continued improvement of antiviral therapies. Interleukin-27 (IL-27) is a pleiotropic cytokine that regulates both innate and adaptive immune responses. Accumulating evidence has revealed potent antiviral activities of IL-27 against numerous viruses, including HIV, influenza, HBV and more. IL-27 contributes to the immune response against viruses indirectly by increasing production of interferons (IFNs) which have various antiviral effects. Additionally, IL-27 can directly interfere with viral infection both by acting similarly to an IFN itself and by modulating the differentiation and function of various immune cells. This review discusses the IFN-dependent and IFN-independent antiviral mechanisms of IL-27 and highlights the potential of IL-27 as a therapeutic cytokine for viral infection.
Topics: Antiviral Agents; Cytokines; Humans; Interferons; Interleukin-27; Virus Diseases
PubMed: 35634328
DOI: 10.3389/fimmu.2022.902853 -
Viruses Apr 2023Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a... (Review)
Review
Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a significant threat to human health. Despite the widespread implementation of several JEV vaccines, the transmission chain of JEV in the natural ecosystem has not changed, and the vector of transmission cannot be eradicated. Therefore, JEV is still the focus of attention for flaviviruses. At present, there is no clinically specific drug for JE treatment. JEV infection is a complex interaction between the virus and the host cell, which is the focus of drug design and development. An overview of antivirals that target JEV elements and host factors is presented in this review. In addition, drugs that balance antiviral effects and host protection by regulating innate immunity, inflammation, apoptosis, or necrosis are reviewed to treat JE effectively.
Topics: Animals; Humans; Encephalitis Virus, Japanese; Antiviral Agents; Ecosystem; Mosquito Vectors; Encephalitis, Japanese
PubMed: 37243122
DOI: 10.3390/v15051033 -
Wiley Interdisciplinary Reviews.... Sep 2022The COVID-19 pandemic has inspired large research investments from the global scientific community in the study of viral properties and antiviral technologies (e.g.,... (Review)
Review
The COVID-19 pandemic has inspired large research investments from the global scientific community in the study of viral properties and antiviral technologies (e.g., self-cleaning surfaces, virucides, antiviral drugs, and vaccines). Emerging viruses are a constant threat due to the substantial variation in viral structures, limiting the potential for expanded broad-spectrum antiviral agent development, and the complexity of targeting multiple and diverse viral species with unique characteristics involving their virulence. Multiple, more infectious variants of SARS-CoV2 (e.g., Delta, Omicron) have already appeared, necessitating research into versatile, robust control strategies in response to the looming threat of future viruses. Nanotechnology and nanomaterials have played a vital role in addressing current viral threats, from mRNA-based vaccines to nanoparticle-based drugs and nanotechnology enhanced disinfection methods. Rapid progress in the field has prompted a review of the current literature primarily focused on nanotechnology-based virucides and antivirals. In this review, a brief description of antiviral drugs is provided first as background with most of the discussion focused on key design considerations for high-efficacy antiviral nanomaterials (e.g., nanopharmaceuticals) as determined from published studies as well as related modes of biological activity. Insights into potential future research directions are also provided with a section devoted specifically to the SARS-CoV2 virus. This article is categorized under: Toxicology and Regulatory Issues in Nanomediciney > Toxicology of Nanomaterials Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.
Topics: Antiviral Agents; Humans; Pandemics; RNA, Viral; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35697665
DOI: 10.1002/wnan.1823 -
Clinical Pharmacokinetics Oct 2017Paritaprevir is a potent hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that is used in combination with other direct-acting antivirals... (Review)
Review
Paritaprevir is a potent hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that is used in combination with other direct-acting antivirals (DAAs) for the treatment of chronic HCV infection. Paritaprevir is primarily metabolized by cytochrome P450 (CYP) 3A4 and is administered with a low dose of ritonavir to achieve drug concentrations suitable for once-daily dosing. Coadministration of paritaprevir with ritonavir increases the half-life of single-dose paritaprevir from approximately 3 h to 5-8 h, doubles the time to maximum plasma concentration (T ) from 2.3 to 4.7 h, and increases exposures 30-fold for maximum observed plasma concentration (C ), 50-fold for area under the plasma concentration-time curve (AUC), and >300-fold for trough concentration (C ). Paritaprevir displays highly variable, nonlinear pharmacokinetics, with C and AUC increasing in a greater than dose proportional manner when administered with or without ritonavir. In the presence of ritonavir, paritaprevir is excreted mostly unchanged in feces via biliary excretion. Paritaprevir exposures are higher in Japanese subjects compared with Caucasian subjects; however, no dose adjustment is needed for Japanese patients as the higher exposures are safe and well tolerated. The pharmacokinetic characteristics of paritaprevir are similar between healthy subjects and HCV-infected patients, and are not appreciably altered by mild or moderate hepatic impairment or mild, moderate, or severe renal impairment, including those on dialysis. Paritaprevir exposures are increased in patients with severe hepatic impairment. Although the presence of a low dose of ritonavir in paritaprevir-containing regimens increases the likelihood of drug-drug interactions, results from several drug interaction studies demonstrated that paritaprevir-containing regimens can be coadministered with many comedications that are commonly prescribed in HCV-infected patients.
Topics: Animals; Antiviral Agents; Clinical Trials as Topic; Cyclopropanes; Drug Interactions; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Proline; Sulfonamides
PubMed: 28236252
DOI: 10.1007/s40262-017-0520-x -
Frontiers in Immunology 2022The central nervous system (CNS) is a constitutive structure of various cell types conserved by anatomical barriers. Many of the major CNS cell-type populations... (Review)
Review
The central nervous system (CNS) is a constitutive structure of various cell types conserved by anatomical barriers. Many of the major CNS cell-type populations distributed across the different brain regions are targets for several neurotropic viruses. Numerous studies have demonstrated that viral susceptibility within the CNS is not absolute and initiates a cell-type specific antiviral defence response. Neurons, astrocytes, and microglial cells are among the major resident cell populations within the CNS and are all equipped to sense viral infection and induce a relative antiviral response mostly through type I IFN production, however, not all these cell types adopt a similar antiviral strategy. Rising evidence has suggested a diversity regarding IFN production and responsiveness based on the cell type/sub type, regional distinction and cell`s developmental state which could shape distinct antiviral signatures. Among CNS resident cell types, neurons are of the highest priority to defend against the invading virus due to their poor renewable nature. Therefore, infected and uninfected glial cells tend to play more dominant antiviral roles during a viral infection and have been found to be the major CNS IFN producers. Alternatively, neuronal cells do play an active part during antiviral responses but may adopt differential strategies in addition to induction of a typical type I IFN response, to minimize the chance of cellular damage. Heterogeneity observed in neuronal IFN responsiveness may be partially explained by their altered ISGs and/or lower STATS expression levels, however, further studies are required to fully elucidate the specificity of the acquired antiviral responses by distinct CNS cell types.
Topics: Central Nervous System; Astrocytes; Microglia; Neuroglia; Antiviral Agents
PubMed: 36458002
DOI: 10.3389/fimmu.2022.1044721