Innate Immunity Research Articles

Utilizing Flaxseed as an Antimicrobial Alternative in Chickens: Integrative Review for Salmonella enterica and Eimeria

This review provides an integrative framework for understanding flaxseed (Linum utassitissimum) as an antimicrobial alternative for poultry production. We begin by familiarizing the reader with the global legislation of antibiotics in animal husbandry; highlighting gaps and current issues for Salmonella enterica (S. enterica) and Eimeria (coccidiosis-inducing). We then discuss the natural, symbiotic characteristics of the Galliformes order (chicken-like birds) and Linum (the flaxes). The key immunological themes in this review include: (i) flaxseed’s regulation of innate and adaptive immunity in chickens, (ii) flaxseed’s ability to accelerate chicken recovery from infection with S. enterica and Eimeria, and (iii) flaxseed’s strengthening of immunity via vitamin B6 antagonism. Research indicates that whole flaxseed increases adaptive immune capacity by augmenting cecal Bacteroides and short-chain fatty acids while also attenuating the heterophil to lymphocyte ratio in chickens. Moreover, flaxseed accelerates chicken recovery from infection with Salmonella Enteritidis or Eimeria tenella; however, future work is needed to better understand (i) defatted flaxseed’s superior performance against Eimeria species and (ii) Eimeria maxima’s resilience against whole flaxseed. In the context of vitamin B6 antagonism, we propose that 15% whole flaxseed overcomes S. enterica’s insult to estrogen synthesis by sustaining the activity of phosphatidylethanolamine methyltransferase (PEMT) in liver. We also propose that 10% defatted flaxseed (as a metformin homologue) strengthens chicken immunity by safeguarding gonadal physiology and by increasing plasma thymidine bioavailability. The concepts in this review can be used as a template for conducting advanced immunological studies in poultry science.

Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative

Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the TLR3 and TLR4 genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (IFNA1, IFNA2, IFNB1, IFNK, and IFNλ1) genes with simultaneous stimulation of the expression of interferon receptor (IFNAR1 and IFNAR2) genes and signalling molecule (JAK1 and ISG15) genes was detected. Increased fold stimulation of the expression of the cytokine genes IL6, TNFA, IL12A, and IL12B was also observed. Thus, it is shown that the XXV is an activator of TLR genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons.

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

Drug Survival and Clinical Course of Patients with Cancer Treated with Biologic Therapy for Psoriasis.

Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special population of cancer patients with psoriasis treated with biologics. Results: As of July 2023, 52 psoriatic patients with a prior/concomitant history of malignancy had taken biologic drugs. The median age was 67 years, and the median age of cancer onset was 55 years. The most common tumors were gastrointestinal cancer and melanoma. After the tumor diagnosis, 61% received an anti-IL17 drug; 37 patients continued the initiated biologic therapy, while 12 switched drugs due to secondary inefficacy. The estimated biologic DS was 55.6% at 50 months. Evidence suggests that IL-17 is a key pathogenic factor involved in tumorigenesis, resulting in a lower risk of malignancies in subjects managed with IL-17 inhibitors. Similarly, IL-23 plays a role in suppressing innate immunity and promoting tumor and metastases development. This is a consistent real-life case series that support the use of biologic drugs in patients with TST. Conclusions: IL-23 and IL-17 inhibitors, being immunomodulators rather than immunosuppressants, may be a safe option for patients in an active oncological setting and for immune-correlated adverse events.

Growth, Nutrient Deposition, Plasma Metabolites, and Innate Immunity Are Associated with Feeding Rate in Juvenile Starry Flounder (Platichthys stellatus).

A 10-week feeding trial was conducted to evaluate the effects of different feeding rates on growth performance, nutrient deposition, plasma metabolite, and immunity of juvenile starry flounder. Fish (initial mean body weight, 183.6 ± 2.3 g) were subjected to eight feeding rates (0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8, and 3.2% body weight/day [BW/d]) with a commercial diet containing 53.5% crude protein and 10.2% crude lipid. After the feeding trial, fish growth increased significantly (p < 0.05) from 0.4% to 2.0% BW/d, with no significant differences being observed beyond 2.0% BW/d. Protein and lipid gains in the whole body and liver of the fish fed 2.0-3.2% BW/d were significantly (p < 0.05) higher than those of the fish fed 0.4% and 0.8% BW/d. Conversely, protein retention in the whole body and the liver decreased with an increased feeding rate. Lysozyme activity was significantly (p < 0.05) higher in the fish fed 1.6-2.8% BW/d than in those fed 0.4-1.2% BW/d. The best-fit model analyses for optimum feeding rate (OFR) revealed that the estimate for each parameter varied between 0.7% (feed conversion ratio) and 3.1% (lipid gain in carcass) BW/d. The OFR for productivity (weight gain) and enhanced innate immunity (lysozyme) were estimated at 2.4% and 1.7% BW/d, respectively.

The regulating role of galectin-9 in immune cell populations.

Galectin-9 (gal-9) is a protein that belongs to the galectin family. Gal-9 is expressed in cells of the innate and adaptive immune system, including lymphocytes, dendritic cells, giant salivary cells, eosinophils and T cells, etc. In different immune cells, the role of gal-9 is different. Gal-9 can induce the proliferation and activation of immune cells, and also promote the apoptosis of immune cells. This effect of gal-9 affects the occurrence and development of a variety of immune-related diseases, such as the invasion of pathogenic microorganisms, immune escape of tumor cells, and inflammatory response. Thus, understanding the biological roles of gal-9 in innate and adaptive immunity may be essential for autoimmune diseases treatment and diagnosis to improve patient quality of life. In this review, we aim to summarize current research on the regulatory roles of gal-9 in human immune system and potential inducers and inhibitors of gal-9, which may provide new strategies for immune diseases therapies.

Research progress on V delta 1+ T cells and their effect on pathogen infection.

The ongoing high occurrence of harmful infectious diseases significantly threatens human health. Existing methods used to control such diseases primarily involve targeting the pathogens, usually neglecting the vital role of host factors in disease advancement. Gamma delta (γδ) T cells act as a bridge between innate and adaptive immunity, playing a crucial role in combating pathogen invasion. Among these γδT cell subsets, which are categorized based on T cell receptor delta variable expression patterns, V delta (δ) 1+ T cells possess unique recognition abilities and regulatory characteristics and actively engage in various immune responses. The differentiation, development, and immune reactivity of Vδ1+ T cells are closely associated with the initial and progressive stages of infectious diseases. This article provides an overview of the classification, distribution, differentiation, and development of Vδ1+ T cells and their mechanisms in combating pathogenic infections, offering new insights for disease diagnosis and treatment.

Alternative substrate kinetics of SARS-CoV-2 Nsp15 endonuclease reveals a specificity landscape dominated by RNA structure.

Coronavirus endoribonuclease Nsp15 contributes to the evasion of host innate immunity by suppressing levels of viral dsRNA. Nsp15 cleaves both ssRNA and dsRNA in vitro with a strong preference for unpaired or bulged U residues, and its activity is stimulated by divalent ions. Here, we systematically quantified effects of RNA sequence and structure context that define its specificity. The results show that sequence preference for U↓A/G, observed previously, contributes only ca. 2-fold to kcat/Km. In contrast, dsRNA structure flanking a bulged U residue increases kcat/Km by an order of magnitude compared to ssRNA while base pairing in dsRNA essentially blocks cleavage. Despite enormous differences in multiple turnover kinetics, the effect of RNA structure on the cleavage step is minimal. Surprisingly, although divalent ion activation of Nsp15 is widely considered to be important for its biological function, the effect on kcat/Km is only ∼2-fold and independent of RNA structure. These results reveal a specificity landscape dominated by RNA structure and provide a quantitative framework for identifying interactions that underlie specificity, determining mechanisms of inhibition and resistance and defining targets important for coronavirus biology.

TMEM173 is a biomarker of predicting prognosis, immune responses and therapeutic effect in human lung adenocarcinoma

The concerns on the function of Transmembrane protein 173 (TMEM173)-dependent innate immunity in prevention and management of cancers has recently been increased. The role of TMEM173 in predicting the prognosis and response to treatment in lung adenocarcinoma (LUAD) remain unclear. Our study revealed that TMEM173 expression was significantly differential in various tumors and the related prognosis was heterogeneous. Further investigation discovered that the expression level of TMEM173 in LUAD tissues was significantly decreased and high TMEM173 expression is associated with better overall survival in LUAD patients. TMEM173 was mainly enriched in immune response-regulating signaling pathway, T cell activation and cell cycle G2/M phase. Furthermore, it was found that TMEM173 expression was positively related to markers and infiltration levels of tumor-infiltrating immune cells. TMEM173 could predict response to targeted therapy, chemotherapy and immunotherapy in LUAD patients. In vitro TMEM173 knockdown decreased the percentage of G2 phase cells, contributing to the increased growth of lung cancer cells. These results implied that TMEM173 might be a prognostic biomarker and a potential target of precision therapy for LUAD patients.

Helicase protein DDX11 as a novel antiviral factor promoting RIG-I-MAVS-mediated signaling pathway.

Innate immunity is the first and most rapid host defense against virus infection. Recognition of viral RNA by the retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs) initiates innate antiviral immune responses. How the binding of viral RNA to and activation of the RLRs are regulated remains enigmatic. In this study, we identified DEAD/H-box helicase 11 (DDX11) as a positive regulator of the RIG-I-mitochondrial antiviral signaling protein (MAVS)-mediated signaling pathways. Mechanistically, we demonstrated that DDX11 bound to viral RNA, interacted with RIG-I, and promoted their binding to viral RNA. DDX11 also promoted the interaction between RIG-I and MAVS and activation of RIG-I-MAVS signaling. Overall, our results elucidate the role of DDX11 in RIG-I-MAVS-dependent signaling pathways and may shed light on innate immune gene regulation.

Etomidate Inhibits Hepatic Ischemia-Reperfusion Injury Depending on the Activation of Nrf2-HO-1 Signaling Pathway.

Hepatic ischemia-reperfusion (I/R) injury (HIRI) is recognized as a local aseptic inflammatory response driven by innate immunity and is considered a leading cause of early organ dysfunction and failure following liver transplantation. Etomidate (Eto), an anesthetic drug known for its ability to inhibit inflammatory response and apoptosis, was the focus of our investigation. In this study, we conducted hepatic I/R surgery invivo on C57 mice, analyzing liver damage through histopathology. Additionally, primary hepatocytes isolated from mice were cultured and subjected to hypoxia/reoxygenation (H/R) insult in vitro, with cell activity assessed using the CCK8 assay and immunofluorescence staining employed to analyze liver inflammatory cell infiltration and apoptosis. Results showed that Eto effectively inhibited liver injury, inflammatory response, and apoptosis induced by HIRI surgery, with the greatest effect observed at an Eto concentration of 10 mg/kg. Furthermore, Eto also showed the ability to inhibit H/R-induced cell damage, inflammatory activation, and apoptosis in primary hepatocytes. Further mechanistic studies revealed that Eto could promote the activation of the Nrf2-HO-1 signaling pathway, and the protective effect of Eto on HIRI was nullified when the Nrf2 inhibitor ML385 was utilized. This study highlights the potential of Eto to protect against HIRI by promoting the Nrf2-HO-1 signaling axis.

The hybrid immunity defined by weaker immune imprinting of people living with HIV has a stronger neutralizing response against Omicron variants. A suggested explanation for fewer symptoms in people living with HIV after SARS-CoV-2 variants breakthrough infection

AimsHuman immunodeficiency virus(HIV) co-infection may cause different immune imprinting, which leads to different hybrid immunity and clinical manifestations of coronavirus disease 2019. This study aims to evaluate the immune imprinting from wild-type(WT) vaccination in people living with HIV(PLWH) and analyze its effect on hybrid immunity and clinical manifestations. Materials and methodsWe enrolled 118 PLWH to compared the differences of BA.5-specific immune response in different immune modes. 20 vaccinated healthy individuals(HC) and 30 vaccinated PLWH were matched to compare the differences of the status of Omicron infection, serum neutralizing antibody levels against WT and BA.5, and specific lymphocytes expression, separately. Key findingsHybrid immunity had a higher level of BA.5 IgG than either vaccine immunity only or natural immunity only in PLWH but didn't have a higher level of BA.5-specific lymphocytes responses. PLWH had fewer symptoms than HC after breakthrough infection. The neutralizing inhibition rate of PLWH was higher for BA.5 and lower for WT, while the neutralizing inhibition rate of HC was higher for WT and lower for BA.5. The difference value of specific B lymphocytes/memory B cells/follicular helper T cells of PLWH was greater than that of HC. SignificanceHybrid immunity of PLWH has a higher level of Omicron-specific IgG without a higher level of Omicron-specific lymphocytes due to immune imprinting. However, there is a stronger neutralizing ability against variants of PLWH due to the weaker immune imprinting of PLWH than that of healthy people, which may lead to fewer symptoms in PLWH after breakthrough infection.

Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer.

The immunostimulatory actions of innate and adaptive immune responses play a crucial role in the cancer-immunity cycle. Although cervical cancer (CC) exhibits a high recurrence rate, the relation with lymphocytes in the tumor tissue have not been analyzed. We analyzed NKT, NK, and T cells, not only in peripheral blood (PB), but also tumor tissue through histological analysis from 23 patients with CC collected before treatment. A correlation of them between PB and the tumor tissue were assessed. We detected functional NKT and NKG2Dhi NK cells and effector CD4+ Tregs in PB. In the tumor, we detected the infiltration of LAG-3+ TIM-3+ CD4+ and CD8+ T cells rather than NK cells particularly in the invasion front (IF) by fluorescent multiplex immunohistochemistry. The heatmap and correlation analysis revealed that LAG-3+ TIM-3+ CD8+ T cells are highly associated with CD69+ CD103- exhausted CD8+ T cells. We identified the statistical relationship between CD4+Tregs in PB and the number of LAG-3+ TIM-3+ CD4+ T cells in the IF, which may be related to recurrence in patients with CC. LAG-3+ TIM-3+ T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.

Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia

Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP is characterized by increased bacterial RNA mass and dominance of culture-confirmed pathogens, detectable days prior to 2°BP clinical diagnosis, and frequently also present in nasal swabs. Assessment of the pulmonary transcriptome reveals suppressed TNFα signaling in patients with 2°BP, and sensitivity analyses suggest this finding is mediated by corticosteroid treatment. Further, we find that increased bacterial RNA mass correlates with reduced expression of innate and adaptive immunity genes in both 2°BP patients and controls. Taken together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP, and suggest that suppressed immune signaling, potentially mediated by corticosteroid treatment, permits expansion of opportunistic bacterial pathogens.

Emerging Role of the p53 Pathway in Modulating Natural Killer Cell Mediated Immunity.

The p53 pathway plays an important role in role in cancer immunity. Mutation or downregulation of the proteins in the p53 pathway are prevalent in many cancers, contributing to tumor progression and immune dysregulation. Recent findings suggest that the activity of p53 within tumor cells, immune cells, and the tumor microenvironment can play an important role modulating natural killer (NK) cell-mediated immunity. Consequently, efforts to restore p53 pathway activity are being actively pursued to modulate this form of immunity. This review focuses on p53 activity regulating the infiltration and the activation of NK cells in the tumor immune microenvironment, which are illustrated in the Graphical Abstract for this review. Furthermore, impact of p53 and its regulation of NK cells on immunogenic cell death within solid tumors and the abscopal effect is reviewed. Finally, future avenues for therapeutically restoring p53 activity to improve NK cell-mediated anti-tumor immunity and optimize the effectiveness of cancer therapies are discussed.

Safety of Zein Nanoparticles on Human Innate Immunity and Inflammation.

In recent years, natural polymers have attracted great interest for the development of release systems for vaccine formulations and drug delivery. Zein, a hydrophobic proline-rich protein mixture obtained from maize, is one of the most widely used polymers, very promising for applications in tissue engineering and the parenteral delivery of bioactive agents. Still, we have a limited understanding of the interaction between zein particles and the human immune system, in particular innate immunity/inflammation, which is the first line of defense of our body. Assessing the immune safety of nanoparticles is of central importance for ensuring that nano-formulations for medical use do not cause adverse effects on human health. Here, we evaluated the capacity of zein nanoparticles to induce/modulate the innate/inflammatory response, the development of innate memory, and the macrophage polarization by using reliable in vitro systems based on human primary monocytes and monocyte-derived macrophages. We observed that zein nanoparticles do not influence any of these aspects of the innate immune/inflammatory response, suggesting its safety and its potential efficiency as a nanocarrier for drug or antigen delivery.

Stimulator of interferon genes (STING) inhibits coronavirus infection by disrupting viral replication organelles.

Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) protein that plays a crucial role in cytosolic DNA-mediated innate immunity. Both STING agonists and antagonists have demonstrated their ability to enhance mouse survival against coronavirus, however, the physiological role of endogenous STING in coronavirus infection remains unclear. Our research unveils that STING inhibits coronavirus replication by impeding the formation of the ER-derived double-membrane vesicles (DMVs), the organelles in which coronavirus replicates. We found that STING was still capable of inhibiting coronavirus OC43 infection in cells, regardless of the knockout of cGAS or MAVS, or blocking type I interferon receptor. Moreover, STING disrupted the interaction between two crucial proteins, NSP4 and NSP6, involved in DMV formation, leading to the disruption of DMV formation. Taken together, our study sheds light on a novel antiviral role of STING in coronavirus infection, elucidating how it disrupts the formation of viral replication organelles, thereby impeding the replication process.

Effects of combined action of proline-rich peptides of human saliva with antimicrobial proteins

BACKGROUND: The substances that make up mixed saliva exhibit activity against bacteria, viruses and fungi. Among them are various cationic antimicrobial peptides: alpha- and beta-defensins, cathelicidins, histatins, but their concentration is relatively low. On the other hand, saliva widely contains a fraction of proline-rich proteins and products of their proteolysis — peptides, the functions of which currently remain poorly studied and unclear. The study of the antimicrobial activity of proline-rich proteins, in particular, when they act together with antimicrobial peptides, and the deciphering of the molecular and cellular basis for the implementation of the protective functions of proline-rich peptides is an urgent task in medicine and biology. The data obtained will help to understand the mechanisms of anti-infective protection of the oral cavity with the participation of the innate immune system, and in the future will allow the creation of drugs based on proline-rich proteins in humans and animals. AIM: Study of the individual antibacterial action of proline-rich salivary proteins, their combined action with the antimicrobial proteins lactoferrin and lysozyme, as well as with one of the most significant endogenous protective peptides — cathelicidin LL-37 on the formation of bacterial biofilms. MATERIALS AND METHODS: Human lactoferrin and egg lysozyme were used in the work. The minimum inhibitory concentrations of peptides against gram-negative and gram-positive bacteria were estimated using serial dilutions in a liquid nutrient medium. Using serial dilutions using the “chessboard” method, it was shown that proline-rich proteins can increase the antibacterial activity of innate immunity peptides present in the oral cavity. The ability of combinations of cationic proline-rich peptides with cathelicidin LL-37 to prevent the formation of bacterial biofilms was studied. RESULTS: In the presence of proline-rich peptides, the antimicrobial activity of some antimicrobial peptides and proteins present in saliva against planktonic bacteria increases. The combined action of proline-rich proteins with LL-37 increases the inhibition of bacterial biofilm formation. CONCLUSIONS: As a result of the study, it was shown that the analyzed cationic proline-rich peptides of human saliva exhibit anti-inflammatory effects, which suggests their significant role in the regulation of inflammatory processes in the oral cavity, as well as their participation in recovery processes.

Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma.

Innate immunity in asthma may be influenced by alterations in lung microbiota, potentially affecting disease severity. This study investigates the differences in lung inflammation and microbiome between asthma-ovalbumin (OVA) administered with and without fluconazole treatment in C57BL/6 mice. Additionally, the role of inflammation was examined in an in vitro study using a pulmonary cell line. At 30 days post-OVA administration, allergic asthma mice exhibited increased levels of IgE and IL-4 in serum and lung tissue, higher pathological scores, and elevated eosinophils in bronchoalveolar lavage fluid (BALF) compared to control mice. Asthma inflammation was characterized by elevated serum IL-6, increased lung cytokines (TNF-α, IL-6, IL-10), and higher fungal abundance confirmed by polymerase chain reaction (PCR). Fluconazole-treated asthma mice displayed higher levels of cytokines in serum and lung tissue (TNF-α and IL-6), increased pathological scores, and a higher number of mononuclear cells in BALF, with undetectable fungal levels compared to untreated mice. Lung microbiome analysis revealed similarities between control and asthma mice; however, fluconazole-treated asthma mice exhibited higher Bacteroidota levels, lower Firmicutes, and reduced bacterial abundance. Pro-inflammatory cytokine production was increased in supernatants of the pulmonary cell line (NCI-H292) after co-stimulation with LPS and beta-glucan (BG) compared to LPS alone. Fluconazole treatment in OVA-induced asthma mice exacerbated inflammation, partially due to fungi and Gram-negative bacteria, as demonstrated by LPS+BG-activated pulmonary cells. Therefore, fluconazole should be reserved for treating fungal asthma rather than asthma caused by other etiologies.

Human cellular restriction factors that target SARS-CoV-2 replication

Millions of people have died and a worldwide economic catastrophe has been brought on by the coronavirus disease 2019 (COVID-19) pandemic. Infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may presently be treated with less than 10 antiviral drugs such as Remdesivir. The need for medical intervention due to sickness has led to unprecedented research efforts to study the biology of coronaviruses. Additionally, there is a strong likelihood that coronaviruses will cause pandemics in the future. All viruses cannot replicate optimally due to host restriction factors. Given that they are genetically more stable than viral targets and may be shared by similar viruses, these antiviral host factors provide appealing targets for antiviral treatment. The identification of antiviral host factors that are a component of human innate immunity and that prevent the completion of the SARS-CoV-2 life cycle has been made possible by the deployment of several “omics” technologies. In this review, we provide an overview of the antiviral host factors that limit the replication of SARS-CoV-2 in this, which were mostly discovered using functional genetic and interactome screening. Important cellular mechanisms for the SARS-CoV-2 life cycle are covered. Finally, we highlight host restriction factors that could be targeted by clinically approved molecules and the induction of these factors as potential antiviral therapies for COVID-19.