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International Journal of Infectious... Dec 2023After the third year of the COVID-19 pandemic, most of the severe COVID-19 burden falls upon immunocompromised patients who cannot mount an endogenous immune response... (Review)
Review
OBJECTIVES
After the third year of the COVID-19 pandemic, most of the severe COVID-19 burden falls upon immunocompromised patients who cannot mount an endogenous immune response after both vaccination and/or natural infection. They also experience persistent SARS-CoV-2 infection with high viral loads often unsuccessfully managed by the standard antiviral monotherapy regimen initially validated for treatment of COVID-19 immunocompetent patients, only. The off-label prescription of such monotherapy regimens in immunocompromised patients is likely to drive the emergence of treatment-related immune escape, relapses, excess morbidity, and mortality from both COVID-19 and delayed treatment of the underlying disorders. A possible treatment approach to mitigate such consequence is based on combined antiviral therapies.
METHODS
We searched PubMed for case reports, case series and clinical trials reporting the usage of combined antiviral therapies for COVID-19.
RESULTS
In this narrative review, we show that combinations of either small molecule antivirals or small molecule antiviral plus passive immunotherapies are safe and effective in small cohorts reported so far.
CONCLUSION
Considering the progressive loss of efficacy of all authorized anti-spike monoclonal antibodies, promising regimen options are reserved to combinations of small molecule antivirals and COVID-19 convalescent plasma from vaccinated donors.
Topics: Humans; COVID-19; SARS-CoV-2; Pandemics; COVID-19 Serotherapy; Antiviral Agents; Immunocompromised Host
PubMed: 37778409
DOI: 10.1016/j.ijid.2023.09.021 -
European Journal of Medicinal Chemistry Sep 2020Viruses continue to be a major threat to human health. In the last century, pandemics occurred and resulted in significant mortality and morbidity. Natural products have... (Review)
Review
Viruses continue to be a major threat to human health. In the last century, pandemics occurred and resulted in significant mortality and morbidity. Natural products have been largely screened as source of inspiration for new antiviral agents. Within the huge class of plant secondary metabolites, resveratrol-derived stilbenoids present a wide structural diversity and mediate a great number of biological responses relevant for human health. However, whilst the antiviral activity of resveratrol has been extensively studied, little is known about the efficacy of its monomeric and oligomeric derivatives. The purpose of this review is to provide an overview of the achievements in this field, with particular emphasis on the source, chemical structures and the mechanism of action of resveratrol-derived stilbenoids against the most challenging viruses. The collected results highlight the therapeutic versatility of stilbene-containing compounds and provide a prospective insight into their potential development as antiviral agents.
Topics: Antiviral Agents; Biological Products; Microbial Sensitivity Tests; Molecular Structure; Stilbenes; Viruses
PubMed: 32652408
DOI: 10.1016/j.ejmech.2020.112541 -
Frontiers in Cellular and Infection... 2022Probiotics exert a variety of beneficial effects, including maintaining homeostasis and the balance of intestinal microorganisms, activating the immune system, and... (Review)
Review
Probiotics exert a variety of beneficial effects, including maintaining homeostasis and the balance of intestinal microorganisms, activating the immune system, and regulating immune responses. Due to the beneficial effects of probiotics, a wide range of probiotics have been developed as probiotic agents for animal and human health. Viral diseases cause serious economic losses to the livestock every year and remain a great challenge for animals. Moreover, strategies for the prevention and control of viral diseases are limited. Viruses enter the host through the skin and mucosal surface, in which are colonized by hundreds of millions of microorganisms. The antiviral effects of probiotics have been proved, including modulation of chemical, microbial, physical, and immune barriers through various probiotics, probiotic metabolites, and host signaling pathways. It is of great significance yet far from enough to elucidate the antiviral mechanisms of probiotics. The major interest of this review is to discuss the antiviral effects and underlying mechanisms of probiotics and to provide targets for the development of novel antivirals.
Topics: Animals; Antiviral Agents; Immune System; Intestines; Probiotics; Viruses
PubMed: 35734576
DOI: 10.3389/fcimb.2022.928050 -
Neuroimmunomodulation 2023The assumption of the pineal hormone melatonin as a therapeutic use for COVID-19-affected people seems promising. Its intake has shown significant improvement in the... (Review)
Review
The assumption of the pineal hormone melatonin as a therapeutic use for COVID-19-affected people seems promising. Its intake has shown significant improvement in the patients' conditions. Higher melatonin titers in children may provide a protective shield against this disease. The hormone melatonin works as an anti-inflammatory, antioxidant, immunomodulator, and strategically slows down the cytokine release which is observed in the COVID-19 disease, thereby improving the overall health of afflicted patients. The medical community is expected shortly to use remedial attributes like anti-inflammatory, antioxidant, antivirals, etc., of melatonin in the successful prevention and cure of COVID-19 morbidity. Thus, the administration of melatonin seems auspicious in the cure and prevention of this COVID-19 fatality. Moreover, melatonin does not seem to reduce the efficiency of approved vaccines against the SARS-CoV-2 virus. Melatonin increases the production of inflammatory cytokines and Th1 and enhances both humoral and cell-mediated responses. Through the enhanced humoral immunity, melatonin exhibits antiviral activities by suppressing multiple inflammatory products such as IL-6, IL1β, and tumor necrosis factor α, which are immediately released during lung injury of severe COVID-19. Hence, the novel use of melatonin along with other antivirals as an early treatment option against COVID-19 infection is suggested. Here, we have chalked out the invasion mechanisms and appropriate implications of the latest findings concerned with melatonin against the virus SARS-CoV-2. Nevertheless, within the setting of a clinical intervention, the promising compounds must go through a series of studies before their recommendation. In the clinical field, this is done in a time-ordered sequence, in line with the phase label affixed to proper protocol of trials: phase I-phase II and the final phase III. Nevertheless, while medical recommendations can only be made on the basis of reassuring evidence, there are still three issues worth considering before implementation: representativeness, validity, and lastly generalizability.
Topics: Child; Humans; COVID-19; Melatonin; SARS-CoV-2; Antioxidants; Antiviral Agents; Anti-Inflammatory Agents
PubMed: 37336193
DOI: 10.1159/000531550 -
Zeitschrift Fur Naturforschung. C,... Sep 2023Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack... (Review)
Review
Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack SOCSs to inhibit Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, block the production and signaling of interferons (IFNs). At the same time, viruses can hijack SOCS to regulate non-IFN factors to evade antiviral response. Host cells can also regulate SOCSs to resist viral infection. The competition of the control of SOCSs may largely determine the fate of viral infection and the susceptibility or resistance of host cells, which is of significance for development of novel antiviral therapies targeting SOCSs. Accumulating evidence reveal that the regulation and function of SOCSs by viruses and host cells are very complicated, which is determined by characteristics of both viruses and host cell types. This report presents a systematic review to evaluate the roles of SOCSs in viral infection and host antiviral responses. One of messages worth attention is that all eight SOCS members should be investigated to accurately characterize their roles and relative contribution in each viral infection, which may help identify the most effective SOCS to be used in "individualized" antiviral therapy.
Topics: Humans; Virus Diseases; Antiviral Agents; Signal Transduction; Immunity, Innate
PubMed: 37233326
DOI: 10.1515/znc-2023-0024 -
Viruses Aug 2022Infection with hepatitis B virus (HBV) is responsible for the increasing global hepatitis burden, with an estimated 296 million people being carriers and living with the... (Review)
Review
Infection with hepatitis B virus (HBV) is responsible for the increasing global hepatitis burden, with an estimated 296 million people being carriers and living with the risk of developing chronic liver disease and cancer. While the current treatment options for chronic hepatitis B (CHB), including oral nucleos(t)ide analogs and systemic interferon-alpha, are deemed suboptimal, the path to finding an ultimate cure for this viral disease is rather challenging. The lack of suitable laboratory animal models that support HBV infection and associated liver disease progression is one of the major hurdles in antiviral drug development. For more than four decades, experimental infection of the Eastern woodchuck with woodchuck hepatitis virus has been applied for studying the immunopathogenesis of HBV and developing new antiviral therapeutics against CHB. There are several advantages to this animal model that are beneficial for performing both basic and translational HBV research. Previous review articles have focused on the value of this animal model in regard to HBV replication, pathogenesis, and immune response. In this article, we review studies of drug development and preclinical evaluation of direct-acting antivirals, immunomodulators, therapeutic vaccines, and inhibitors of viral entry, gene expression, and antigen release in the woodchuck model of CHB since 2014 until today and discuss their significance for clinical trials in patients.
Topics: Animals; Antiviral Agents; Disease Models, Animal; Drug Development; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Marmota
PubMed: 36016334
DOI: 10.3390/v14081711 -
Current Opinion in Virology Jun 2016Influenza A and B viruses are major causes for respiratory infections in children and adults. Viral and host factors determine clinical manifestations which range from... (Review)
Review
Influenza A and B viruses are major causes for respiratory infections in children and adults. Viral and host factors determine clinical manifestations which range from self-resolving uncomplicated infections, severe viral or bacterial secondary pneumonia, to death. Emergence of transmissible resistant variants and time-dependent effectiveness are the major challenges for the currently approved antivirals, M2 ion channel blockers and neuraminidase (NA) inhibitors. Favipiravir that inhibits the RNA-dependent RNA polymerase of multiple RNA viruses is approved in Japan against influenza strains resistant to available antivirals. With expanded knowledge on viral nucleoprotein (NP) and polymerase structures, novel small molecule inhibitors targeting NP oligomer formation, PA endonuclease domain, and the PB2 cap-binding domain are being developed. Combination therapy with different antiviral compounds or with host immune response modulators may further benefit clinical outcomes.
Topics: Amides; Antiviral Agents; Drug Resistance, Viral; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Influenza A virus; Influenza B virus; Influenza, Human; Neuraminidase; Nucleoproteins; Pyrazines; Respiratory Tract Infections; Virus Replication
PubMed: 27344481
DOI: 10.1016/j.coviro.2016.05.004 -
European Journal of Medicinal Chemistry Jan 2024The COVID-19 pandemic is caused by SARS-CoV-2, an RNA virus with high transmissibility and mutation rate. Given the paucity of orally bioavailable antiviral drugs to...
The COVID-19 pandemic is caused by SARS-CoV-2, an RNA virus with high transmissibility and mutation rate. Given the paucity of orally bioavailable antiviral drugs to combat SARS-CoV-2 infection, there is a critical need for additional antivirals with alternative mechanisms of action. Papain-like protease (PL) is one of the two SARS-CoV-2 encoded viral cysteine proteases essential for viral replication. PL cleaves at three sites of the viral polyproteins. In addition, PL antagonizes the host immune response upon viral infection by cleaving ISG15 and ubiquitin from host proteins. Therefore, PL is a validated antiviral drug target. In this study, we report the X-ray crystal structures of papain-like protease (PL) with two potent inhibitors, Jun9722 and Jun9843. Subsequently, we designed and synthesized several series of analogs to explore the structure-activity relationship, which led to the discovery of PL inhibitors with potent enzymatic inhibitory activity and antiviral activity against SARS-CoV-2. Together, the lead compounds are promising drug candidates for further development.
Topics: Humans; Papain; COVID-19; SARS-CoV-2; Pandemics; Antiviral Agents; Protease Inhibitors
PubMed: 38065031
DOI: 10.1016/j.ejmech.2023.116011 -
International Journal of Molecular... May 2023Type I and III Interferons (IFNs) are the first lines of defense in microbial infections. They critically block early animal virus infection, replication, spread, and... (Review)
Review
Type I and III Interferons (IFNs) are the first lines of defense in microbial infections. They critically block early animal virus infection, replication, spread, and tropism to promote the adaptive immune response. Type I IFNs induce a systemic response that impacts nearly every cell in the host, while type III IFNs' susceptibility is restricted to anatomic barriers and selected immune cells. Both IFN types are critical cytokines for the antiviral response against epithelium-tropic viruses being effectors of innate immunity and regulators of the development of the adaptive immune response. Indeed, the innate antiviral immune response is essential to limit virus replication at the early stages of infection, thus reducing viral spread and pathogenesis. However, many animal viruses have evolved strategies to evade the antiviral immune response. The are viruses with the largest genome among the RNA viruses. - (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic. The virus has evolved numerous strategies to contrast the IFN system immunity. We intend to describe the virus-mediated evasion of the IFN responses by going through the main phases: First, the molecular mechanisms involved; second, the role of the genetic background of IFN production during SARS-CoV-2 infection; and third, the potential novel approaches to contrast viral pathogenesis by restoring endogenous type I and III IFNs production and sensitivity at the sites of infection.
Topics: Animals; Interferons; SARS-CoV-2; COVID-19; Antiviral Agents; Interferon Type I; Cytokines; Immunity, Innate; Immune Evasion
PubMed: 37298304
DOI: 10.3390/ijms24119353 -
Methods in Molecular Biology (Clifton,... 2023The general interest in the study of the interplay between peroxisomes and viruses has increased in recent years, with different reports demonstrating that distinct... (Review)
Review
The general interest in the study of the interplay between peroxisomes and viruses has increased in recent years, with different reports demonstrating that distinct viruses modulate peroxisome-related mechanisms to either counteract the cellular antiviral response or support viral propagation. Nevertheless, mechanistical details are still scarce, and information is often incomplete. In this chapter, we present an overview of the current knowledge concerning the interplay between peroxisomes and different viruses. We furthermore present, compare, and discuss the most relevant experimental approaches and tools used in the different studies. Finally, we stress the importance of further, more detailed, and spatial-temporal analyses that encompass all the different phases of the viruses' infection cycles. These studies may lead to the discovery of novel peroxisome-related cellular mechanisms that can further be explored as targets for the development of novel antiviral therapies.
Topics: Peroxisomes; Antiviral Agents; Viruses
PubMed: 36952192
DOI: 10.1007/978-1-0716-3048-8_19