Botanical Drugs and Supplements Affecting the Immune Response in the Time of COVID-19: Implications for Research and Clinical Practice

In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday selfcare and health care, and since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, and specifically regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and anti-inflammatory effect include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.

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Mathematical Modeling of Within-Host, Untreated, Cytomegalovirus Infection Dynamics after Allogeneic Transplantation

Viruses ◽

10.3390/v13112292 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2292

Author(s):

Elizabeth R. Duke ◽

Florencia A. T. Boshier ◽

Michael Boeckh ◽

Joshua T. Schiffer ◽

E. Fabian Cardozo-Ojeda

Keyword(s):

Mathematical Modeling ◽

Immune Response ◽

Target Cell ◽

Hematopoietic Cell Transplantation ◽

Viral Infections ◽

Immune Cell ◽

Controlled Trial ◽

Antiviral Treatment ◽

Serum Samples ◽

Cell Compartments

Cytomegalovirus (CMV) causes significant morbidity and mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Whereas insights gained from mathematical modeling of other chronic viral infections such as HIV, hepatitis C, and herpes simplex virus-2 have aided in optimizing therapy, previous CMV modeling has been hindered by a lack of comprehensive quantitative PCR viral load data from untreated episodes of viremia in HCT recipients. We performed quantitative CMV DNA PCR on stored, frozen serum samples from the placebo group of participants in a historic randomized controlled trial of ganciclovir for the early treatment of CMV infection in bone marrow transplant recipients. We developed four main ordinary differential Equation mathematical models and used model selection theory to choose between 38 competing versions of these models. Models were fit using a population, nonlinear, mixed-effects approach. We found that CMV kinetics from untreated HCT recipients are highly variable. The models that recapitulated the observed patterns most parsimoniously included explicit, dynamic immune cell compartments and did not include dynamic target cell compartments, consistent with the large number of tissue and cell types that CMV infects. In addition, in our best-fitting models, viral clearance was extremely slow, suggesting severe impairment of the immune response after HCT. Parameters from our best model correlated well with participants’ clinical risk factors and outcomes from the trial, further validating our model. Our models suggest that CMV dynamics in HCT recipients are determined by host immune response rather than target cell limitation in the absence of antiviral treatment.

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Eating NAFTA

10.1525/california/9780520291805.001.0001 ◽

2018 ◽

Cited By ~ 21

Author(s):

Alyshia Gálvez

Keyword(s):

Public Health ◽

Chronic Disease ◽

Low Income ◽

Food System ◽

Dietary Habits ◽

Trade Agreement ◽

Well Being ◽

Health Crisis ◽

The North ◽

The World

In the two decades since the North American Free Trade Agreement (NAFTA) went into effect, Mexico has seen an epidemic of diet-related illness. While globalization has been associated with an increase in chronic disease around the world, in Mexico, the speed and scope of the rise has been called a public health emergency. The shift in Mexican foodways is happening at a moment when the country’s ancestral cuisine is now more popular and appreciated around the world than ever. What does it mean for their health and well-being when many Mexicans eat fewer tortillas and more instant noodles, while global elites demand tacos made with handmade corn tortillas? This book examines the transformation of the Mexican food system since NAFTA and how it has made it harder for people to eat as they once did. The book contextualizes NAFTA within Mexico’s approach to economic development since the Revolution, noticing the role envisioned for rural and low-income people in the path to modernization. Examination of anti-poverty and public health policies in Mexico reveal how it has become easier for people to consume processed foods and beverages, even when to do so can be harmful to health. The book critiques Mexico’s strategy for addressing the public health crisis generated by rising rates of chronic disease for blaming the dietary habits of those whose lives have been upended by the economic and political shifts of NAFTA.

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Therapeutic Exploitation of Viral Interference

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190405140858 ◽

2020 ◽

Vol 20 (4) ◽

pp. 423-432 ◽

Cited By ~ 1

Author(s):

Imre Kovesdi ◽

Tibor Bakacs

Keyword(s):

Broad Spectrum ◽

Viral Infections ◽

Viral Vector ◽

Antiviral Treatment ◽

Type I ◽

Virus Infections ◽

Emerging Viruses ◽

Viral Interference ◽

Pathogenic Virus ◽

Hepatitis C Rna

: Viral interference, originally, referred to a state of temporary immunity, is a state whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. : For the functional cure of persistent viral infections and for the development of broad- spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double- stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could, therefore, be developed into a biological platform for a new “one drug, multiple bugs” broad-spectrum antiviral treatment approach.

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Prebiotic Carbohydrates for Therapeutics.

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200929140522 ◽

2020 ◽

Vol 20 ◽

Author(s):

Renuka Basavaiah ◽

Prapulla Siddalingaiya Gurudutt

Keyword(s):

Immune Response ◽

Lipid Metabolism ◽

Bacterial Infection ◽

Food Industry ◽

Health Benefits ◽

Well Being ◽

Intestinal Disease ◽

Mineral Absorption ◽

Health Promoting ◽

Insulin Dependent

: The food industry is constantly shifting focus based on prebiotics as health-promoting substrates rather than just food supplements. A prebiotic is ‘‘a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health.” Prebiotics exert a plethora of health-promoting effects, which has lead to the establishment of multimillion food and pharma industries. The following are the health benefits attributed to prebiotics: mineral absorption, better immune response, increased resistance to bacterial infection, improved lipid metabolism, possible protection against cancer, relief from poor digestion of lactose, and reduction in the risk of diseases such as intestinal disease, non-insulin dependent diabetes, obesity and allergy. Numerous studies in both animals and humans have demonstrated the health benefits of prebiotics.

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Novel Applications of Nanotechnology in Controlling HIV and HSV Infections

Current Drug Research Reviews ◽

10.2174/2589977512999201124121931 ◽

2020 ◽

Vol 12 ◽

Author(s):

Sai Akilesh M ◽

Ashish Wadhwani

Keyword(s):

Drug Delivery ◽

Viral Infections ◽

Polymeric Nanoparticles ◽

Volume Ratio ◽

Fold Increase ◽

Multi Drug Resistance ◽

Health Crisis ◽

Pharmaceutical Properties ◽

Simplex Virus ◽

The Impact

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.

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IgA Vasculitis: Etiology, Treatment, Biomarkers and Epigenetic Changes

International Journal of Molecular Sciences ◽

10.3390/ijms22147538 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7538

Author(s):

Hitomi Sugino ◽

Yu Sawada ◽

Motonobu Nakamura

Keyword(s):

Immune Response ◽

Autoimmune Diseases ◽

Organ Dysfunction ◽

Human Body ◽

Therapeutic Approach ◽

Viral Infections ◽

External Environment ◽

Iga Vasculitis ◽

Epigenetic Changes ◽

Flexible Response

IgA, previously called Henoch-Schönlein vasculitis, is an essential immune component that drives the host immune response to the external environment. As IgA has the unique characteristic of a flexible response to broad types of microorganisms, it sometimes causes an autoreactive response in the host human body. IgA vasculitis and related organ dysfunction are representative IgA-mediated autoimmune diseases; bacterial and viral infections often trigger IgA vasculitis. Recent drug developments and the presence of COVID-19 have revealed that these agents can also trigger IgA vasculitis. These findings provide a novel understanding of the pathogenesis of IgA vasculitis. In this review, we focus on the characteristics of IgA and symptoms of IgA vasculitis and other organ dysfunction. We also mention the therapeutic approach, biomarkers, novel triggers for IgA vasculitis, and epigenetic modifications in patients with IgA vasculitis.

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Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

Indian Journal of Clinical Biochemistry ◽

10.1007/s12291-021-00961-6 ◽

2021 ◽

Author(s):

Karthick Dharmalingam ◽

Amandeep Birdi ◽

Sojit Tomo ◽

Karli Sreenivasulu ◽

Jaykaran Charan ◽

...

Keyword(s):

Immune Response ◽

Trace Elements ◽

Viral Entry ◽

Viral Infections ◽

Inhibitory Effect ◽

Antioxidants Activity ◽

Host Immune Responses ◽

Complex Interactions ◽

Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

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521. Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.715 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S326-S327

Author(s):

Simone A Thair ◽

Yudong He ◽

Yehudit Hasin-Brumshtein ◽

Suraj Sakaram ◽

Rushika R Pandya ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

Nk Cells ◽

Pathway Analysis ◽

Host Response ◽

Viral Infections ◽

Cell Types ◽

Gene Signature ◽

Gene Signatures ◽

Similarities And Differences

Abstract Background COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections. Methods We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1, FDR ≤ 0.05%. Results Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1). Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1). Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56dim NK cells & memory B cells and eosinophils (Fig3). Figure 1 Figure 2 Figure 3 Conclusion The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2. Disclosures Simone A. Thair, PhD, Inflammatix, Inc. (Employee, Shareholder) Yudong He, PhD, Inflammatix Inc. (Employee) Yehudit Hasin-Brumshtein, PhD, Inflammatix (Employee, Shareholder) Suraj Sakaram, MS in Biochemistry and Molecular Biology, Inflammatix (Employee, Other Financial or Material Support, stock options) Rushika R. Pandya, MS, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Timothy Sweeney, MD, PHD, Inflammatix, Inc. (Employee, Shareholder)

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Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Genes ◽

10.3390/genes12071041 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1041

Author(s):

Mohammad Tarek ◽

Hana Abdelzaher ◽

Firas Kobeissy ◽

Hassan A. N. El-Fawal ◽

Mohammed M. Salama ◽

...

Keyword(s):

Immune Response ◽

Genetic Factors ◽

Bioinformatics Analysis ◽

Expression Patterns ◽

Spike Protein ◽

Target Cells ◽

Health Crisis ◽

Expression Levels ◽

Different Populations ◽

Shed Light

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

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Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

Antibiotics ◽

10.3390/antibiotics10010092 ◽

2021 ◽

Vol 10 (1) ◽

pp. 92 ◽

Cited By ~ 2

Author(s):

Alessia Catalano ◽

Domenico Iacopetta ◽

Michele Pellegrino ◽

Stefano Aquaro ◽

Carlo Franchini ◽

...

Keyword(s):

Anticancer Agents ◽

Kinase Inhibitors ◽

Viral Infections ◽

Drug Repositioning ◽

Biological Activities ◽

Antiviral Treatment ◽

Far East ◽

Mild Disease ◽

To Come ◽

The Uk

Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.

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