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Cell Reports Jul 2022Plasmacytoid dendritic cells (pDCs) are specialized cells of the immune system that are thought to be the main cellular source of type I interferon alpha (IFNα) in... (Review)
Review
Plasmacytoid dendritic cells (pDCs) are specialized cells of the immune system that are thought to be the main cellular source of type I interferon alpha (IFNα) in response to viral infections. IFNs are powerful antivirals, whereas defects in their function or induction lead to impaired resistance to virus infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. IFN production needs to be controlled, because sustained IFN production can also have detrimental effects on disease outcome. As such, pDCs are likely important for acute antiviral protection against SARS-CoV-2 infection but could potentially also contribute to chronic IFN levels. Here, we provide a historical overview of pDC biology and summarize existing literature addressing their involvement and importance during viral infections of the airways. Furthermore, we outline recent reports focused on the potential role of pDCs during SARS-CoV-2 infection, as well as the potential for this cellular subset to impact COVID-19 disease outcome.
Topics: Antiviral Agents; COVID-19; Dendritic Cells; Humans; Interferon Type I; SARS-CoV-2
PubMed: 35858624
DOI: 10.1016/j.celrep.2022.111148 -
Pathology Oncology Research : POR Jan 2015The association between hepatitis C virus and certain B-cell non-Hodgkin lymphomas, such as marginal zone lymphomas, is supported by epidemiological studies. The exact... (Review)
Review
The association between hepatitis C virus and certain B-cell non-Hodgkin lymphomas, such as marginal zone lymphomas, is supported by epidemiological studies. The exact pathogenetic mechanism is still unknown but both chronic antigenic stimulation and viral lymphotropism may contribute to the evolution of the malignant clone. Furthermore, the hematologic response following hepatitis C antiviral treatment suggests that the virus may have an etiologic role. Interferon and ribavirin based treatment proved to be successful in small case series of hepatitis C virus associated splenic lymphoma with villous lymphocytes, therefore, it is suggested that antiviral treatment could be an alternative to chemo-immunotherapy. In the near future new more potent direct acting antivirals will make interferon free treatments possible. It is still an open question whether these new short-course regimens are also effective in the treatment of associated lymphomas and what is the importance of the lymphoid reservoir in eliminating HCV.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Humans; Lymphoma, Non-Hodgkin
PubMed: 25273531
DOI: 10.1007/s12253-014-9845-z -
The Interplay of Genital Herpes with Cellular Processes: A Pathogenesis and Therapeutic Perspective.Viruses Oct 2023Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular... (Review)
Review
Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular processes, from harnessing host machinery for replication to subverting antiviral defenses like autophagy and programmed cell death, exemplifies the intricate interplay at the heart of its pathogenesis. While the biomedical community has extensively researched antiviral interventions, the efficiency of these strategies in managing HSV-2 remains suboptimal. Recognizing this, attention has shifted toward leveraging host cellular components to regulate HSV-2 replication and influence the cell cycle. Furthermore, innovative interventional strategies-including drug repurposing, microbivacs, connecting the host microbiome, and exploiting natural secondary metabolites-are emerging as potential game changers. This review summarizes the key steps in HSV-2 pathogenesis and newly discovered cellular interactions, presenting the latest developments in the field, highlighting existing challenges, and offering a fresh perspective on HSV-2's pathogenesis and the potential avenues for its treatment by targeting cellular proteins and pathways.
Topics: Humans; Herpes Genitalis; Herpesvirus 2, Human; Autophagy; Antiviral Agents; Herpes Simplex
PubMed: 38005873
DOI: 10.3390/v15112195 -
Cold Spring Harbor Perspectives in... Apr 2021In the last few years, several new direct-acting influenza antivirals have been licensed, and others have advanced in clinical development. The increasing diversity of... (Review)
Review
In the last few years, several new direct-acting influenza antivirals have been licensed, and others have advanced in clinical development. The increasing diversity of antiviral classes should allow an adequate public health response should a resistant virus to one agent or class widely circulate. One new antiviral, baloxavir marboxil, has been approved in the United States for treatment of influenza in those at high risk of developing influenza-related complications. Except for intravenous zanamivir in European Union countries, no antivirals have been licensed specifically for the indication of severe influenza or hospitalized influenza. This review addresses recent clinical developments involving selected polymerase inhibitors, neuraminidase inhibitors, antibody-based therapeutics, and host-directed therapies. There are many knowledge gaps for most of these agents because some data are not published and multiple pivotal studies are in progress at present. This review also considers important clinical research issues, including regulatory pathways, study designs, endpoints, and target populations encountered during the clinical development of novel therapeutics.
Topics: Antiviral Agents; Drug Development; Drug Resistance, Viral; Humans; Influenza, Human; Nucleic Acid Synthesis Inhibitors
PubMed: 32041763
DOI: 10.1101/cshperspect.a038463 -
Nature Communications Nov 2023Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic...
Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic acid sensors such as cGAMP synthase (cGAS) along with several other antiviral response pathways. Yet most of these immunomodulators are expressed very early in infection while many are variable host range determinants, and significant gaps remain in our understanding of poxvirus sensing and evasion strategies. Here, we show that after infection is established, subsequent progression of the viral lifecycle is sensed through specific changes to mitochondria that coordinate distinct aspects of the antiviral response. Unlike other viruses that cause extensive mitochondrial damage, poxviruses sustain key mitochondrial functions including membrane potential and respiration while reducing reactive oxygen species that drive inflammation. However, poxvirus replication induces mitochondrial hyperfusion that independently controls the release of mitochondrial DNA (mtDNA) to prime nucleic acid sensors and enables an increase in glycolysis that is necessary to support interferon stimulated gene (ISG) production. To counter this, the poxvirus F17 protein localizes to mitochondria and dysregulates mTOR to simultaneously destabilize cGAS and block increases in glycolysis. Our findings reveal how the poxvirus F17 protein disarms specific mitochondrially orchestrated responses to later stages of poxvirus replication.
Topics: Poxviridae; Cytoplasm; Nucleotidyltransferases; Antiviral Agents; Nucleic Acids
PubMed: 38036506
DOI: 10.1038/s41467-023-43635-y -
Biomolecules Aug 2021In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The... (Review)
Review
In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.
Topics: Animals; Antiviral Agents; Coronavirus; Flavonoids; Humans; Immunologic Factors; Phytochemicals; Protease Inhibitors; COVID-19 Drug Treatment
PubMed: 34439920
DOI: 10.3390/biom11081254 -
Letters in Applied Microbiology Sep 2022There is a need for new effective antivirals, particularly in response to the development of antiviral drug resistance and emerging RNA viruses such as SARS-CoV-2.... (Review)
Review
There is a need for new effective antivirals, particularly in response to the development of antiviral drug resistance and emerging RNA viruses such as SARS-CoV-2. Plants are a significant source of structurally diverse bioactive compounds for drug discovery suggesting that plant-derived natural products could be developed as antiviral agents. This article reviews the antiviral activity of plant-derived natural products against RNA viruses, with a focus on compounds targeting specific stages of the viral life cycle. A range of plant extracts and compounds have been identified with antiviral activity, often against multiple virus families suggesting they may be useful as broad-spectrum antiviral agents. The antiviral mechanism of action of many of these phytochemicals is not fully understood and there are limited studies and clinical trials demonstrating their efficacy and toxicity in vivo. Further research is needed to evaluate the therapeutic potential of plant-derived natural products as antiviral agents.
Topics: Animals; Antiviral Agents; Biological Products; Life Cycle Stages; Plant Extracts; RNA Viruses; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34953146
DOI: 10.1111/lam.13637 -
Postepy Higieny I Medycyny... Sep 2015Influenza virus neuraminidase inhibitors (NAIs), including oseltamivir, zanamivir and peramivir, are important antivirals for the treatment and prophylaxis of influenza.... (Review)
Review
Influenza virus neuraminidase inhibitors (NAIs), including oseltamivir, zanamivir and peramivir, are important antivirals for the treatment and prophylaxis of influenza. Increasing use of NAIs brings into focus the risk of drug resistance. The problem of resistance is of high clinical and epidemiological importance. There are generally three levels of antiviral resistance according to the way that resistance can be detected or inferred: genotypic, phenotypic and clinical resistance. Recently the problem of resistance to NAIs, although still rare (<2% of influenza isolates), has been rising. It should be underlined that NAI resistance in influenza viruses is relative, and despite its presence patients with resistant viruses may still benefit from receiving NAIs. The clinical resistance and the response to treatment with antivirals remain the most important proof of antiviral effectiveness. Currently, there has not been observed cross-resistance between oseltamivir and zanamivir, which may be a consequence of the number of given doses, differences in drug structure and duration of the drug concentrations in the site of infection. Early treatment with appropriate doses of NAI is necessary to minimize the likelihood of a resistant virus arising.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Child, Preschool; Drug Resistance, Viral; Enzyme Inhibitors; Female; Humans; Infant; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Neuraminidase; Oseltamivir; Young Adult; Zanamivir
PubMed: 26400894
DOI: No ID Found -
Viruses Jul 2019Parvovirus B19 (B19V) is a human pathogenic virus, responsible for an ample range of clinical manifestations. Infections are usually mild, self-limiting, and controlled... (Review)
Review
Parvovirus B19 (B19V) is a human pathogenic virus, responsible for an ample range of clinical manifestations. Infections are usually mild, self-limiting, and controlled by the development of a specific immune response, but in many cases clinical situations can be more complex and require therapy. Presently available treatments are only supportive, symptomatic, or unspecific, such as administration of intravenous immunoglobulins, and often of limited efficacy. The development of antiviral strategies against B19V should be considered of highest relevance for increasing the available options for more specific and effective therapeutic treatments. This field of research has been explored in recent years, registering some achievements as well as interesting future perspectives. In addition to immunoglobulins, some compounds have been shown to possess inhibitory activity against B19V. Hydroxyurea is an antiproliferative drug used in the treatment of sickle-cell disease that also possesses inhibitory activity against B19V. The nucleotide analogues Cidofovir and its lipid conjugate Brincidofovir are broad-range antivirals mostly active against dsDNA viruses, which showed an antiviral activity also against B19V. Newly synthesized coumarin derivatives offer possibilities for the development of molecules with antiviral activity. Identification of some flavonoid molecules, with direct inhibitory activity against the viral non-structural (NS) protein, indicates a possible line of development for direct antiviral agents. Continuing research in the field, leading to better knowledge of the viral lifecycle and a precise understanding of virus-cell interactions, will offer novel opportunities for developing more efficient, targeted antiviral agents, which can be translated into available therapeutic options.
Topics: Animals; Antiviral Agents; Disease Susceptibility; Drug Development; Erythema Infectiosum; Genome, Viral; Genomics; Host-Pathogen Interactions; Humans; Immunization, Passive; Parvovirus B19, Human; Virus Replication
PubMed: 31323869
DOI: 10.3390/v11070659 -
Hepatology Communications May 2022Chronic hepatitis B virus (HBV) infection remains difficult to cure due to the persistent, self-replenishing nature of the viral genome and impaired host immune... (Review)
Review
Chronic hepatitis B virus (HBV) infection remains difficult to cure due to the persistent, self-replenishing nature of the viral genome and impaired host immune responses. Current treatment goals for chronic hepatitis B (CHB) are to prevent or significantly delay liver-related adverse outcomes and death, and two types of treatments are available: nucleos(t)ide analogues (NAs) and interferons (IFNs). NAs effectively suppress HBV replication, and IFNs improve serological response rates, thereby decreasing the risk of adverse outcomes. However, their efficacy in attaining serological responses, especially functional cure (i.e., loss of serum hepatitis B surface antigen), is very limited. Various strategies such as stopping antiviral therapy or combining therapies have been investigated to enhance response, but efficacy is only modestly improved. Importantly, the development of novel direct-acting antivirals and immunomodulators is underway to improve treatment efficacy and enhance rates of functional cure. The present review provides an overview of the treatment goals and indications, the possibility of expanding indications, and the safety and efficacy of different treatment strategies involving established and/or novel therapies as we continue our search for a cure.
Topics: Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Interferons
PubMed: 34894108
DOI: 10.1002/hep4.1875