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Seminars in Immunology Jun 2019Outbreaks of severe virus infections with the potential to cause global pandemics are increasing. In many instances these outbreaks have been newly emerging (SARS... (Review)
Review
Outbreaks of severe virus infections with the potential to cause global pandemics are increasing. In many instances these outbreaks have been newly emerging (SARS coronavirus), re-emerging (Ebola virus, Zika virus) or zoonotic (avian influenza H5N1) virus infections. In the absence of a targeted vaccine or a pathogen-specific antiviral, broad-spectrum antivirals would function to limit virus spread. Given the direct antiviral effects of type I interferons (IFNs) in inhibiting the replication of both DNA and RNA viruses at different stages of their replicative cycles, and the effects of type I IFNs on activating immune cell populations to clear virus infections, IFNs-α/β present as ideal candidate broad-spectrum antivirals.
Topics: Animals; Antiviral Agents; Communicable Disease Control; Coronavirus; Disease Outbreaks; Ebolavirus; Host-Pathogen Interactions; Humans; Influenza A Virus, H5N1 Subtype; Interferons; Virus Diseases; Virus Replication
PubMed: 31771760
DOI: 10.1016/j.smim.2019.101300 -
Frontiers in Bioscience (Scholar... Jan 2010Rapid increase in drug-resistant influenza virus isolates, and pandemic threat posed by highly pathogenic avian influenza A and swine flu viruses provide clear and... (Review)
Review
Rapid increase in drug-resistant influenza virus isolates, and pandemic threat posed by highly pathogenic avian influenza A and swine flu viruses provide clear and compelling reasons for fast tracking development of novel antiviral drugs. Nucleic acid-based drugs represent a promising class of novel antiviral agents that can be designed to target various seasonal, pandemic and avian influenza viruses. Nucleic acids can be designed to elicit broad-spectrum antiviral responses in the host, by suppressing viral gene expression, or by inducing cleavage or degradation of viral RNA. Immunomodulating nucleic acids, such as double stranded RNA and CpG oligonucleotides, can be potent anti-influenza agents that work by eliciting protective innate and adaptive immunity in the host. By activating the toll-like receptor signaling pathways, these drugs can activate the host's antiviral and inflammatory defenses to combat influenza viruses. Antisense oligonucleotides, small interfering RNAs (siRNA), and nanoRNAs represent sequence specific gene-silencing approaches that could be deployed to suppress or inhibit viral protein gene expression. Lastly, catalytic nucleic acids such as DNAzymes and/or ribozymes can suppress viral replication by repeatedly cleaving viral mRNAs and template RNAs. In summary, nucleic acid-based antiviral agents are versatile, diverse and could complement existing antiviral drugs in combating influenza.
Topics: Antiviral Agents; DNA, Catalytic; Gene Expression Regulation, Viral; Gene Silencing; Humans; Influenza A virus; Influenza, Human; Nucleic Acids; Oligonucleotides, Antisense; RNA, Small Interfering; RNA, Viral; Signal Transduction; Toll-Like Receptors; Virus Replication
PubMed: 20036985
DOI: 10.2741/s102 -
Journal of Ethnopharmacology Oct 2022The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well with utmost safety and effectiveness. It is well researched that herbal medicines or natural products have shown promising outcomes to strengthen immunity with antiviral potential against SARS-COV-2.
AIM OF THE REVIEW
Our objective is to provide a comprehensive insight into the preventive and therapeutic effects of herbal medicines and products (Ayurvedic) for pre-and post-COVID manifestations.
MATERIAL AND METHOD
The database used in the text is collected and compiled from Scopus, PubMed, Nature, Elsevier, Web of Science, bioRxiv, medRxiv, American Chemical Society, and clinicaltrials.gov up to January 2022. Articles from non-academic sources such as websites and news were also retrieved. Exploration of the studies was executed to recognize supplementary publications of research studies and systematic reviews. The keywords, such as "SARS-COV-2, coronavirus, COVID-19, herbal drugs, immunity, herbal immunomodulators, infection, herbal antiviral drugs, and WHO recommendation" were thoroughly searched. Chemical structures were drawn using the software Chemdraw Professional 15.0.0.160 (PerkinElmer Informatics, Inc.).
RESULT
A plethora of literature supports that the use of herbal regimens not only strengthen immunity but can also treat SARS-COV-2 infection with minimal side effects. This review summarizes the mechanistic insights into herbal therapy engaging interferons and antibodies to boost the response against SARS-COV-2 infection, several clinical trials, and in silico studies (computational approaches) on selected natural products including, Ashwagandha, Guduchi, Yashtimadhu, Tulsi, etc. as preventive and therapeutic measures against COVID. We have also emphasized the exploitation of herbal medicine-based pharmaceutical products along with perspectives for unseen upcoming alike diseases.
CONCLUSION
According to the current state of art and cutting-edge research on herbal medicines have showed a significant promise as modern COVID tools. Since vaccination cannot be purported as a long-term cure for viral infections, herbal/natural medicines can only be considered a viable alternative to current remedies, as conceived from our collected data to unroot recurring viral infections.
Topics: Antiviral Agents; Comprehension; Drugs, Chinese Herbal; Humans; Plants, Medicinal; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35654349
DOI: 10.1016/j.jep.2022.115420 -
Frontiers in Immunology 2023Cellular metabolism plays a central role in the regulation of both innate and adaptive immunity. Immune cells utilize metabolic pathways to modulate the cellular... (Review)
Review
Cellular metabolism plays a central role in the regulation of both innate and adaptive immunity. Immune cells utilize metabolic pathways to modulate the cellular differentiation or death. The intricate interplay between metabolism and immune response is critical for maintaining homeostasis and effective antiviral activities. In recent years, immunometabolism induced by viral infections has been extensively investigated, and accumulating evidence has indicated that cellular metabolism can be hijacked to facilitate viral replication. Generally, virus-induced changes in cellular metabolism lead to the reprogramming of metabolites and metabolic enzymes in different pathways (glucose, lipid, and amino acid metabolism). Metabolic reprogramming affects the function of immune cells, regulates the expression of immune molecules and determines cell fate. Therefore, it is important to explore the effector molecules with immunomodulatory properties, including metabolites, metabolic enzymes, and other immunometabolism-related molecules as the antivirals. This review summarizes the relevant advances in the field of metabolic reprogramming induced by viral infections, providing novel insights for the development of antivirals.
Topics: Humans; Antiviral Agents; Viruses; Metabolic Networks and Pathways; Immunity; Virus Diseases
PubMed: 37559723
DOI: 10.3389/fimmu.2023.1228811 -
Journal of Virology Jun 2022Effective broad-spectrum antivirals are critical to prevent and control emerging human coronavirus (hCoV) infections. Despite considerable progress made toward...
Effective broad-spectrum antivirals are critical to prevent and control emerging human coronavirus (hCoV) infections. Despite considerable progress made toward identifying and evaluating several synthetic broad-spectrum antivirals against hCoV infections, a narrow therapeutic window has limited their success. Enhancing the endogenous interferon (IFN) and IFN-stimulated gene (ISG) response is another antiviral strategy that has been known for decades. However, the side effects of pegylated type-I IFNs (IFN-Is) and the proinflammatory response detected after delayed IFN-I therapy have discouraged their clinical use. In contrast to IFN-Is, IFN-λ, a dominant IFN at the epithelial surface, has been shown to be less proinflammatory. Consequently, we evaluated the prophylactic and therapeutic efficacy of IFN-λ in hCoV-infected airway epithelial cells and mice. Human primary airway epithelial cells treated with a single dose of IFN-I (IFN-α) and IFN-λ showed similar ISG expression, whereas cells treated with two doses of IFN-λ expressed elevated levels of ISG compared to that of IFN-α-treated cells. Similarly, mice treated with two doses of IFN-λ were better protected than mice that received a single dose, and a combination of prophylactic and delayed therapeutic regimens completely protected mice from a lethal Middle East respiratory syndrome CoV (MERS-CoV) infection. A two-dose IFN-λ regimen significantly reduced lung viral titers and inflammatory cytokine levels with marked improvement in lung inflammation. Collectively, we identified an effective regimen for IFN-λ use and demonstrated the protective efficacy of IFN-λ in MERS-CoV-infected mice. Effective antiviral agents are urgently required to prevent and treat individuals infected with SARS-CoV-2 and other emerging viral infections. The COVID-19 pandemic has catapulted our efforts to identify, develop, and evaluate several antiviral agents. However, a narrow therapeutic window has limited the protective efficacy of several broad-spectrum and CoV-specific antivirals. IFN-λ is an antiviral agent of interest due to its ability to induce a robust endogenous antiviral state and low levels of inflammation. Here, we evaluated the protective efficacy and effective treatment regimen of IFN-λ in mice infected with a lethal dose of MERS-CoV. We show that while prophylactic and early therapeutic IFN-λ administration is protective, delayed treatment is detrimental. Notably, a combination of prophylactic and delayed therapeutic administration of IFN-λ protected mice from severe MERS. Our results highlight the prophylactic and therapeutic use of IFN-λ against lethal hCoV and likely other viral lung infections.
Topics: Animals; Antiviral Agents; Coronavirus Infections; Humans; Interferons; Mice; Middle East Respiratory Syndrome Coronavirus; Interferon Lambda
PubMed: 35588276
DOI: 10.1128/jvi.00364-22 -
British Medical Bulletin Sep 2019Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances.
BACKGROUND
Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances.
SOURCES OF DATA
Sources of data are recently published research papers and reviews about HCMV treatments.
AREAS OF AGREEMENT
Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved by the FDA and EMA.
AREAS OF CONTROVERSY
Should we screen newborns for HCMV, and use antivirals to treat sensorineural hearing loss after congenital HCMV infection?
GROWING POINTS
Growing points are developing drugs against latently infected cells. In addition to small molecule inhibitors, a chemokine-based fusion toxin protein, F49A-FTP, has shown promise in killing both lytically and latently infected cells.
AREAS TIMELY FOR DEVELOPING RESEARCH
We need to understand what immune responses are required to control HCMV, and how best to raise these immune responses with a vaccine.
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Drug Development; Early Diagnosis; Hematopoietic Stem Cell Transplantation; Humans; Immunity, Cellular; Immunoglobulins; Immunosuppression Therapy; Infant, Newborn; Organ Transplantation; Perinatal Care; Virus Latency
PubMed: 31580403
DOI: 10.1093/bmb/ldz031 -
Virology Journal Jun 2023The ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred... (Review)
Review
The ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred despite drastic containment measures, and this number is still increasing. Currently, no standard therapies for COVID-19 are available, which necessitates identifying effective preventive and therapeutic agents against COVID-19. However, developing new drugs and vaccines is a time-consuming process, and therefore, repurposing the existing drugs or redeveloping related targets seems to be the best strategy to develop effective therapeutics against COVID-19. Autophagy, a multistep lysosomal degradation pathway contributing to nutrient recycling and metabolic adaptation, is involved in the initiation and progression of numerous diseases as a part of an immune response. The key role of autophagy in antiviral immunity has been extensively studied. Moreover, autophagy can directly eliminate intracellular microorganisms by selective autophagy, that is, "xenophagy." However, viruses have acquired diverse strategies to exploit autophagy for their infection and replication. This review aims to trigger the interest in the field of autophagy as an antiviral target for viral pathogens (with an emphasis on COVID-19). We base this hypothesis on summarizing the classification and structure of coronaviruses as well as the process of SARS-CoV-2 infection and replication; providing the common understanding of autophagy; reviewing interactions between the mechanisms of viral entry/replication and the autophagy pathways; and discussing the current state of clinical trials of autophagy-modifying drugs in the treatment of SARS-CoV-2 infection. We anticipate that this review will contribute to the rapid development of therapeutics and vaccines against COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Antiviral Agents; Autophagy
PubMed: 37328875
DOI: 10.1186/s12985-023-02069-0 -
International Journal of Molecular... May 2021COVID-19 is a respiratory disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease at first was identified in the... (Review)
Review
COVID-19 is a respiratory disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease at first was identified in the city of Wuhan, China in December 2019. Being a human infectious disease, it causes high fever, cough, breathing problems. In some cases it can be fatal, especially in people with comorbidities like heart or kidney problems and diabetes. The current COVID-19 treatment is based on symptomatic therapy, so finding an appropriate drug against COVID-19 remains an immediate and crucial target for the global scientific community. Two main processes are thought to be responsible for the COVID-19 pathogenesis. In the early stages of infection, disease is determined mainly by virus replication. In the later stages of infection, by an excessive immune/inflammatory response, leading to tissue damage. Therefore, the main treatment options are antiviral and immunomodulatory/anti-inflammatory agents. Many clinical trials have been conducted concerning the use of various drugs in COVID-19 therapy, and many are still ongoing. The majority of trials examine drug reposition (repurposing), which seems to be a good and effective option. Many drugs have been repurposed in COVID-19 therapy including remdesivir, favipiravir, tocilizumab and baricitinib. The aim of this review is to highlight (based on existing and accessible clinical evidence on ongoing trials) the current and available promising drugs for COVID-19 and outline their characteristics.
Topics: Anti-Inflammatory Agents; Antiviral Agents; COVID-19; Drug Repositioning; Humans; Pharmaceutical Preparations; SARS-CoV-2; Virus Replication; COVID-19 Drug Treatment
PubMed: 34063964
DOI: 10.3390/ijms22115434 -
Expert Opinion on Pharmacotherapy 2016Hepatitis C virus (HCV) is a chronic infection that disproportionately impacts people living with HIV. In the past, HCV therapy was less effective in individuals with... (Review)
Review
INTRODUCTION
Hepatitis C virus (HCV) is a chronic infection that disproportionately impacts people living with HIV. In the past, HCV therapy was less effective in individuals with HIV co-infection. However, the advent of direct-acting antivirals has revolutionized HCV treatment with high rates of success in patients both with and without HIV.
AREAS COVERED
In this paper, we review the evidence supporting the use of ledipasvir and sofosbuvir (LDV/SOF) for the treatment of HCV in patients with HIV co-infection. Articles searchable on MEDLINE/PubMed were reviewed to provide context for use of LDV/SOF in individuals with HCV and HIV co-infection.
EXPERT OPINION
This treatment is highly effective in achieving HCV cure or sustained virologic response, however further studies need to done to address efficacy of treatment in people with uncontrolled HIV, concerns regarding drug-interactions with antiretroviral therapy, and potential for shorter duration treatment.
Topics: Antiviral Agents; Benzimidazoles; Coinfection; Drug Interactions; Drug Resistance, Viral; Drug Therapy, Combination; Fluorenes; HIV Infections; Hepatitis C, Chronic; Humans; Sofosbuvir
PubMed: 26898158
DOI: 10.1517/14656566.2016.1157580 -
Frontiers in Immunology 2019Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections... (Review)
Review
Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections remains limited and is challenged by the virus itself. While vaccination is the preferred intervention strategy against influenza, its efficacy is reduced in the elderly and infants who are most susceptible to severe and/or fatal infections. In addition, antigenic variation of IAV complicates the production of efficacious vaccines. Similarly, effectiveness of currently used antiviral drugs is jeopardized by the development of resistance to these drugs. Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections. While host-factors have long been recognized as attractive therapeutic candidates against other viruses, only recently they have been targeted for development as IAV antivirals. Future strategies to combat IAV infections will most likely include approaches that alter host-virus interactions on the one hand or dampen harmful host immune responses on the other, with the use of biological response modifiers (BRMs). In principle, BRMs are biologically active agents including antibodies, small peptides, and/or other (small) molecules that can influence the immune response. BRMs are already being used in the clinic to treat malignancies and autoimmune diseases. Repurposing such agents would allow for accelerated use against severe and potentially fatal IAV infections. In this review, we will address the potential therapeutic use of different BRM classes to modulate the immune response induced after IAV infections.
Topics: Animals; Antiviral Agents; Host-Pathogen Interactions; Humans; Immunologic Factors; Immunomodulation; Influenza A virus; Influenza, Human; Treatment Outcome
PubMed: 31031778
DOI: 10.3389/fimmu.2019.00809