scholarly journals Cellular and Molecular Immunology Approaches for the Development of Immunotherapies against the New Coronavirus (SARS-CoV-2): Challenges to Near-Future Breakthroughs

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Juliana Gil Melgaço ◽  
Danielle Brito e Cunha ◽  
Tamiris Azamor ◽  
Andrea Marques Vieira da Silva ◽  
Luciana Neves Tubarão ◽  
...  
Keyword(s):  
Viral Disease ◽  
Mortality Rates ◽  
Innate Immune ◽  
Host Factors ◽  
Severe Damage ◽  
Scientific Communities ◽  
Molecular Immunology ◽  
Virus Interaction ◽  
Hemostatic Disorders ◽  
Near Future

The severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2), termed COVID-19, has been highlighted as the most important infectious disease of our time, without a vaccine and treatment available until this moment, with a big impact on health systems worldwide, and with high mortality rates associated with respiratory viral disease. The medical and scientific communities have also been confronted by an urgent need to better understand the mechanism of host-virus interaction aimed at developing therapies and vaccines. Since this viral disease can trigger a strong innate immune response, causing severe damage to the pulmonary tract, immunotherapies have also been explored as a means to verify the immunomodulatory effect and improve clinical outcomes, whilst the comprehensive COVID-19 immunology still remains under investigation. In this review, both cellular and molecular immunopathology as well as hemostatic disorders induced by SARS-CoV-2 are summarized. The immunotherapeutic approaches based on the most recent clinical and nonclinical studies, emphasizing their effects for the treatment of COVID-19, are also addressed. The information presented elucidates helpful insights aiming at filling the knowledge gaps around promising immunotherapies that attempt to control the dysfunction of host factors during the course of this infectious viral disease.

scholarly journals Innate Immune DNA Sensing of Flaviviruses

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 979
Author(s):  
Tongtong Zhu ◽  
Ana Fernandez-Sesma
Keyword(s):  
Innate Immune System ◽  
Rna Viruses ◽  
Innate Immune ◽  
Host Factors ◽  
Dna Sensing ◽  
Antiviral Responses ◽  
Sensory Pathways ◽  
Sensing System ◽  
Positive Sense ◽  
Successful Replication

Flaviviruses are arthropod-borne RNA viruses that have been used extensively to study host antiviral responses. Often selected just to represent standard single-stranded positive-sense RNA viruses in early studies, the Flavivirus genus over time has taught us how truly unique it is in its remarkable ability to target not just the RNA sensory pathways but also the cytosolic DNA sensing system for its successful replication inside the host cell. This review summarizes the main developments on the unexpected antagonistic strategies utilized by different flaviviruses, with RNA genomes, against the host cyclic GAMP synthase (cGAS)/stimulator of interferon genes (STING) cytosolic DNA sensing pathway in mammalian systems. On the basis of the recent advancements on this topic, we hypothesize that the mechanisms of viral sensing and innate immunity are much more fluid than what we had anticipated, and both viral and host factors will continue to be found as important factors contributing to the host innate immune system in the future.

scholarly journals Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

Science ◽  
2020 ◽  
Vol 370 (6521) ◽  
pp. eabe9403 ◽  
Author(s):  
David E. Gordon ◽  
Joseph Hiatt ◽  
Mehdi Bouhaddou ◽  
Veronica V. Rezelj ◽  
Svenja Ulferts ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Global Economy ◽  
Molecular Mechanisms ◽  
Protein Localization ◽  
Viral Disease ◽  
Host Factors ◽  
Protein Protein Interaction ◽  
Chaperone Protein ◽  
Cryo Electron Microscopy ◽  
Drug Treatments

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo–electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

scholarly journals Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance

2020 ◽  
Vol 8 (7) ◽  
pp. 1024
Author(s):  
Carolina Reis Zambom ◽  
Fauller Henrique da Fonseca ◽  
Saulo Santesso Garrido
Keyword(s):  
Drug Targets ◽  
Extracellular Enzymes ◽  
Innate Immune ◽  
Host Protein ◽  
Histatin 5 ◽  
Salivary Peptide ◽  
Current Review ◽  
Adaptive Mechanisms ◽  
Antifungal Peptides ◽  
Near Future

Candida albicans is a common microorganism of human’s microbiota and can be easily found in both respiratory and gastrointestinal tracts as well as in the genitourinary tract. Approximately 30% of people will be infected by C. albicans during their lifetime. Due to its easy adaptation, this microorganism started to present high resistance to antifungal agents which is associated with their indiscriminate use. There are several reports of adaptive mechanisms that this species can present. Some of them are intrinsic alteration in drug targets, secretion of extracellular enzymes to promote host protein degradation and efflux receptors that lead to a diminished action of common antifungal and host’s innate immune response. The current review aims to bring promising alternatives for the treatment of candidiasis caused mainly by C. albicans. One of these alternatives is the use of antifungal peptides (AFPs) from the Histatin family, like histatin-5. Besides that, our focus is to show how nanotechnology can allow the application of these peptides for treatment of this microorganism. In addition, our intention is to show the importance of nanoparticles (NPs) for this purpose, which may be essential in the near future.

The innate immune roles of host factors TRIM5α and Cyclophilin A on HIV-1 replication

2015 ◽  
Vol 204 (5) ◽  
pp. 557-565 ◽  
Author(s):  
Yi-Qun Kuang ◽  
Hong-Liang Liu ◽  
Yong-Tang Zheng
Keyword(s):  
Cyclophilin A ◽  
Innate Immune ◽  
Host Factors ◽  
Hiv 1

The pharmacology of endosomal TLR agonists in viral disease

2007 ◽  
Vol 35 (6) ◽  
pp. 1468-1472 ◽  
Author(s):  
D.R. Averett ◽  
S.P. Fletcher ◽  
W. Li ◽  
S.E. Webber ◽  
J.R. Appleman
Keyword(s):  
Viral Disease ◽  
Therapeutic Benefit ◽  
Innate Immune ◽  
Clinical Effects ◽  
Tlr Agonists ◽  
Tlr7 Agonist ◽  
Interferon Induction ◽  
Natural Ligands ◽  
Clinical Profiles

The discovery of endosomal TLRs (Toll-like receptors) and their natural ligands has accelerated efforts to exploit them for therapeutic benefit. Importantly, this was preceded by clinical exploration of agents now known to be endosomal TLR agonists. Clinical effects in viral disease have been reported with agonists of TLR3, TLR7, TLR7/8 and TLR9, and the TLR7 agonist imiquimod is marketed for topical use against warts, a papillomavirus disease. The observed pre-clinical and clinical profiles of agonists of each of these TLRs suggest induction of a multifaceted innate immune response, with biomarker signatures indicative of type 1 interferon induction. However, these agents differ in both their pharmaceutical characteristics and the cellular distribution of their target TLRs, suggesting that drugs directed to these targets will display differences in their overall pharmacological profiles.

scholarly journals A Debate on Vitamin C: Supplementation on the Hotline for COVID-19

2020 ◽  
Vol 11 (3) ◽  
pp. 395-396
Author(s):  
Ata Mahmoodpoor ◽  
Ali Shamekh ◽  
Sarvin Sanaie
Keyword(s):  
Vitamin C ◽  
Respiratory Distress ◽  
Innate Immune System ◽  
Defense Mechanisms ◽  
Distress Syndrome ◽  
Viral Disease ◽  
The Body ◽  
Innate Immune ◽  
Vitamin C Supplementation ◽  
Almost All

SARS-CoV-2 causes acute respiratory distress syndrome. As any other newly emerged viral disease, there are no definite and curative treatments available for the COVID-19 till now, so almost all of the available therapies are designed to support the body against the virus. A healthy and complete nutrition provides the resources to the body’s defense mechanisms. Vitamin C supplementation has shown promising results in the activation of the innate immune system and may protect against respiratory viral diseases. Here, we briefly discuss about its role in critically ill patients, respiratory distress, sepsis and possible role in COVID-19.

Coagulation and innate immune responses: can we view them separately?

Blood ◽  
2009 ◽  
Vol 114 (12) ◽  
pp. 2367-2374 ◽  
Author(s):  
Mieke Delvaeye ◽  
Edward M. Conway
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Horseshoe Crab ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Living Fossil ◽  
Potential Impact ◽  
Hemostatic Disorders ◽  
New Strategies

Abstract The horseshoe crab is often referred to as a “living fossil,” representative of the oldest classes of arthropods, almost identical to species in existence more than 500 million years ago. Comparative analyses of the defense mechanisms used by the horseshoe crab that allowed it to survive mostly unchanged throughout the millennia reveal a common ancestry of the coagulation and innate immune systems that are totally integrated—indeed, almost inseparable. In human biology, we traditionally view the hemostatic pathways and those regulating innate immune responses to infections and tissue damage as entirely separate entities. But are they? The last couple of decades have revealed a remarkable degree of interplay between these systems, and the linking cellular and molecular mechanisms are rapidly being delineated. In this review, we present some of the major points of intersection between coagulation and innate immunity. We attempt to highlight the potential impact of these findings by identifying recently established paradigms that will hopefully result in the emergence of new strategies to treat a range of inflammatory and hemostatic disorders.

scholarly journals Resistance induction based on the understanding of molecular interactions between plant viruses and host plants

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Md. Shamim Akhter ◽  
Kenji S. Nakahara ◽  
Chikara Masuta
Keyword(s):  
Genome Editing ◽  
Viral Disease ◽  
Resistance Mechanisms ◽  
Plant Viruses ◽  
Host Factors ◽  
Viral Resistance ◽  
Main Body ◽  
Cellular Functions ◽  
New Type ◽  
Resistance Spectrum

Abstract Background Viral diseases cause significant damage to crop yield and quality. While fungi- and bacteria-induced diseases can be controlled by pesticides, no effective approaches are available to control viruses with chemicals as they use the cellular functions of their host for their infection cycle. The conventional method of viral disease control is to use the inherent resistance of plants through breeding. However, the genetic sources of viral resistance are often limited. Recently, genome editing technology enabled the publication of multiple attempts to artificially induce new resistance types by manipulating host factors necessary for viral infection. Main body In this review, we first outline the two major (R gene-mediated and RNA silencing) viral resistance mechanisms in plants. We also explain the phenomenon of mutations of host factors to function as recessive resistance genes, taking the eIF4E genes as examples. We then focus on a new type of virus resistance that has been repeatedly reported recently due to the widespread use of genome editing technology in plants, facilitating the specific knockdown of host factors. Here, we show that (1) an in-frame mutation of host factors necessary to confer viral resistance, sometimes resulting in resistance to different viruses and that (2) certain host factors exhibit antiviral resistance and viral-supporting (proviral) properties. Conclusion A detailed understanding of the host factor functions would enable the development of strategies for the induction of a new type of viral resistance, taking into account the provision of a broad resistance spectrum and the suppression of the appearance of resistance-breaking strains.

scholarly journals Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate 

2020 ◽  
Author(s):  
Lutfiye Karcıoğlu Batur ◽  
Nezih Hekim
Keyword(s):  
Mortality Rate ◽  
Inflammatory Response ◽  
Gene Polymorphisms ◽  
Public Awareness ◽  
Mortality Rates ◽  
Host Factors ◽  
Cytokine Storm ◽  
High Frequencies ◽  
Severity Of Disease ◽  
Immune Profiling

Abstract The pathogenesis of COVID-19 implicates a potent inflammatory response resulting in cytokine storm. We aimed to evaluate association between polymorphisms in IL-6 gene at rs1800796/rs1800795, IL-6R at rs2228145, IL-10 at rs1800896 and rs1800871, IL-17 at rs2275913 and rs76378, and the prevalence (per million) and mortality rates (per million) of COVID-19 among populations of China, Japan, India, Iran, Spain, Italy, Mexico, Netherlands, Sweden, Turkey, Finland, Brazil, Czechia, Russia, Poland. AG and GG genotypes of rs2275913 in IL-17A was found to be correlated with prevalence and mortality rates, especially in Spain and Brazil populations (p<0.05) while TT genotype of rs763780 in IL-17F was not dependent on the high frequencies in all populations. However, the polymorphisms in IL-6, IL-6R and IL-10 appear not to be correlated with prevalence and mortality rates. The variations in the prevalence of COVID-19 and its mortality rates among countries may be explained by cytokine storm differed by the polymorphisms of rs2275913 locus in IL-17A gene. However, the prevalence of infection differs from severity of COVID-19, based on many factors such as public awareness, behaviors and antiviral policy of countries. Yet, the severity of disease induced by viral infection might be associated with genetic host factors including immune profiling.

scholarly journals Regulatory Innate Lymphoid Cells: A new subset of innate immune lymphocytes with more potential functions to be discovered in immune regulation

2020 ◽  
Vol 3 (01) ◽  
Author(s):  
Jifeng Yu
Keyword(s):  
Immune Regulation ◽  
Myeloid Leukemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Innate Lymphoid Cells ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Immune Lymphocytes ◽  
Regulatory Functions ◽  
Near Future

Regulatory innate lymphoid cells (ILCregs) are a newly identified subset of innate immune lymphocytes. The discovery of this subset cell has revealed several inhibitory and stimulatory pathways that affect the regulatory functions of ILCregs, in addition to miRNA and other genetic molecular regulations. These pathways may play important roles in the pathogenesis and potential immunotherapy in patients with different kind of diseases, such as inflammation and ischemia / reperfusion injury of the kidney, acute myeloid leukemia, through immunomodulatory and anti-inflammatory pathway, as well as miRNA regulations. Further studies on ILCregs may be a potentially high interest in the near future.

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