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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 -
International Journal of Molecular... Sep 2022The innate immune system facilitates defense mechanisms against pathogen invasion and cell damage. Toll-like receptors (TLRs) assist in the activation of the innate... (Review)
Review
The innate immune system facilitates defense mechanisms against pathogen invasion and cell damage. Toll-like receptors (TLRs) assist in the activation of the innate immune system by binding to pathogenic ligands. This leads to the generation of intracellular signaling cascades including the biosynthesis of molecular mediators. TLRs on cell membranes are adept at recognizing viral components. Viruses can modulate the innate immune response with the help of proteins and RNAs that downregulate or upregulate the expression of various TLRs. In the case of COVID-19, molecular modulators such as type 1 interferons interfere with signaling pathways in the host cells, leading to an inflammatory response. Coronaviruses are responsible for an enhanced immune signature of inflammatory chemokines and cytokines. TLRs have been employed as therapeutic agents in viral infections as numerous antiviral Food and Drug Administration-approved drugs are TLR agonists. This review highlights the therapeutic approaches associated with SARS-CoV-2 and the TLRs involved in COVID-19 infection.
Topics: Antiviral Agents; Chemokines; Cytokines; Humans; Immunity, Innate; Interferon Type I; Ligands; SARS-CoV-2; Toll-Like Receptors; COVID-19 Drug Treatment
PubMed: 36142620
DOI: 10.3390/ijms231810716 -
Cellular and Molecular Gastroenterology... 2022The persistence of viral covalently closed circular DNA (cccDNA) is the major obstacle for antiviral treatment against hepatitis B virus (HBV). Basic and translational...
BACKGROUND AND AIMS
The persistence of viral covalently closed circular DNA (cccDNA) is the major obstacle for antiviral treatment against hepatitis B virus (HBV). Basic and translational studies are largely hampered due to the lack of feasible small animal models to support HBV cccDNA formation. The aim of this study is to establish a novel mouse model harboring cccDNA.
METHODS
An adeno-associated virus (AAV) vector carrying a replication-deficient HBV1.04-fold genome (AAV-HBV1.04) was constructed. The linear HBV genome starts from nucleotide 403 and ends at 538, which results in the splitting of HBV surface and polymerase genes. Different HBV replication markers were evaluated for AAV-HBV1.04 plasmid-transfected cells, the AAV-HBV1.04 viral vector-transduced cells, and mice injected with the AAV-HBV1.04 viral vector.
RESULTS
Compared with the previously reported AAV-HBV1.2 construct, direct transfection of AAV-HBV1.04 plasmid failed to produce hepatitis B surface antigen and progeny virus. Interestingly, AAV-HBV1.04 viral vector transduction could result in the formation of cccDNA and the production of all HBV replication markers in vitro and in vivo. The formation of cccDNA could be blocked by ATR (ataxia-telangiectasia and Rad3-related protein) inhibitors but not HBV reverse transcription inhibitor or capsid inhibitors. The AAV-HBV1.04 mouse supported long-term HBV replication and responded to antiviral treatments.
CONCLUSIONS
This AAV-HBV1.04 mouse model can support HBV cccDNA formation through ATR-mediated DNA damage response. The de novo formed cccDNA but not the parental AAV vector can lead to the production of hepatitis B surface antigen and HBV progeny. This model will provide a unique platform for studying HBV cccDNA and developing novel antivirals against HBV infection.
Topics: Animals; Antiviral Agents; DNA, Circular; DNA, Viral; Dependovirus; Disease Models, Animal; Hepatitis B Surface Antigens; Hepatitis B virus; Mice; Virus Replication
PubMed: 34896285
DOI: 10.1016/j.jcmgh.2021.11.011 -
Cells Dec 2020Currently, an efficient treatment for COVID-19 is still unavailable, and people are continuing to die from complications associated with SARS-CoV-2 infection. Thus, the... (Review)
Review
Currently, an efficient treatment for COVID-19 is still unavailable, and people are continuing to die from complications associated with SARS-CoV-2 infection. Thus, the development of new therapeutic approaches is urgently needed, and one alternative is to target the mechanisms of autophagy. Due to its multifaceted role in physiological processes, many questions remain unanswered about the possible advantages of inhibiting or activating autophagy. Based on a search of the literature in this field, a novel analysis has been made to highlight the relation between the mechanisms of autophagy in antiviral and inflammatory activity in contrast with those of the pathogenesis of COVID-19. The present analysis reveals a remarkable coincidence between the uncontrolled inflammation triggered by SARS-CoV-2 and autophagy defects. Particularly, there is conclusive evidence about the substantial contribution of two concomitant factors to the development of severe COVID-19: a delayed or absent type I and III interferon (IFN-I and IFN-III) response together with robust cytokine and chemokine production. In addition, a negative interplay exists between autophagy and an IFN-I response. According to previous studies, the clinical decision to inhibit or activate autophagy should depend on the underlying context of the pathological timeline of COVID-19. Several treatment options are herein discussed as a guide for future research on this topic.
Topics: Anti-Inflammatory Agents; Antiviral Agents; Autophagy; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33322168
DOI: 10.3390/cells9122679 -
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 -
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 -
Bioorganic & Medicinal Chemistry Aug 2017Arthropod-borne viruses (arboviruses) are an important threat to human and animal health globally. Among these, zoonotic diseases account for billions of cases of human... (Review)
Review
Arthropod-borne viruses (arboviruses) are an important threat to human and animal health globally. Among these, zoonotic diseases account for billions of cases of human illness and millions of deaths every year, representing an increasing public health problem. Chikungunya virus belongs to the genus Alphavirus of the family Togariridae, and is transmitted mainly by the bite of female mosquitoes of the Aedes aegypti and/or A. albopictus species. The focus of this review will be on the medicinal chemistry of Chikungunya virus, including synthetic and natural products, as well as rationally designed compounds.
Topics: Animals; Antiviral Agents; Biological Products; Chemistry, Pharmaceutical; Chikungunya Fever; Chikungunya virus; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship
PubMed: 28689975
DOI: 10.1016/j.bmc.2017.06.049 -
Pharmacology & Therapeutics May 2022Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop... (Review)
Review
Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop uncontrolled spread of these pathogens and mitigate their socio-economic impact globally. This can be achieved through drug repurposing, which tackles inherent time- and resource-consuming processes associated with conventional drug discovery and development. In this review, we examine key preclinical and clinical therapeutic and prophylactic approaches that have been applied for treatment of SARS-CoV-2 infection. We break these strategies down into virus- versus host-targeting and discuss their reported efficacy, advantages, and disadvantages. Importantly, we highlight emerging evidence on application of host serine protease-inhibiting anticoagulants, such as nafamostat mesylate, as a potentially powerful therapy to inhibit virus activation and offer cross-protection against multiple strains of coronavirus, lower inflammatory response independent of its antiviral effect, and modulate clotting problems seen in COVID-19 pneumonia.
Topics: Anticoagulants; Antiviral Agents; Humans; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34718070
DOI: 10.1016/j.pharmthera.2021.108027 -
Emerging Microbes & Infections Dec 2022The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to humanity.... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to humanity. SARS-CoV-2 invades host cells, causing a failure of host immune recognition. Instead of an effective antiviral immunological response after SARS-CoV-2 invasion, the cascading pathological syndrome of COVID-19, especially in severe disease, is exacerbated by an overt inflammatory response and the suppression of SARS-CoV-2-specific immune responses. As is known, excessive inflammation leads to pathophysiological changes in virus-infected tissues or organs, manifested by imbalanced immune responses, cytokine storm, and aggressive neutrophil activation, ultimately leading to lung damage, such as alveolar damage, endotheliitis, and fluid overload. However, the triggers and consequences of a disruption to immune system homeostasis and the underlying mechanisms of uncontrolled immunopathology following viral infection remain unclear. Here, we review the dynamic and systemic immune progression from an imbalance in cell-mediated immune responses to COVID-19 lung injury. Our understanding of key mechanisms involved in pathogenesis is critical for the development of therapeutic agents and to optimize therapeutic strategies.
Topics: Antiviral Agents; COVID-19; Humans; Immunity; Pandemics; SARS-CoV-2
PubMed: 36069182
DOI: 10.1080/22221751.2022.2122579