Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.

Introduction: Severe dengue is thought to be caused by an excessive host immune response. Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre+Ifnarflox/flox mice carrying depleted Ifnar expression only in subsets of murine myeloid cells. Results: Although dengue virus (DENV) clinical isolates were not virulent in LysM Cre+Ifnarflox/flox mice, mouse-adapted DV1-5P7Sp and DV3P12/08P4Bm, which were obtained by passaging the spleen or bone marrow of mice, demonstrated 100% lethality with severe vascular leakage in the liver and small intestine. DV1-5P7Sp and DV3P12/08P4Bm harbored five and seven amino acid substitutions, respectively. Infection also induced neutrophil infiltration in the small intestine, and increased expression of IL-6 and MMP-8 and blockade of TNF-α signaling protected the mice, as demonstrated in a previous severe dengue mouse model using C57/BL6 mice lacking both IFN-α/ß and IFN-γ receptors. Notably, the new models with DV1-5P7Sp and DV3P12/08P4Bm showed an increased proliferative capacity of the adapted viruses in the thymus and bone marrow. Discussion: These observations suggest that myeloid cell infection is sufficient to trigger cytokine storm-induced vascular leakage. This model can refine the factors involved in the pathology of severe dengue leading to vascular leakage.

Transcriptional precision in photoreceptor development and diseases - Lessons from 25 years of CRX research.

The vertebrate retina is made up of six specialized neuronal cell types and one glia that are generated from a common retinal progenitor. The development of these distinct cell types is programmed by transcription factors that regulate the expression of specific genes essential for cell fate specification and differentiation. Because of the complex nature of transcriptional regulation, understanding transcription factor functions in development and disease is challenging. Research on the Cone-rod homeobox transcription factor CRX provides an excellent model to address these challenges. In this review, we reflect on 25 years of mammalian CRX research and discuss recent progress in elucidating the distinct pathogenic mechanisms of four CRX coding variant classes. We highlight how in vitro biochemical studies of CRX protein functions facilitate understanding CRX regulatory principles in animal models. We conclude with a brief discussion of the emerging systems biology approaches that could accelerate precision medicine for CRX-linked diseases and beyond.

What contributes to disability in progressive MS? A brain and cervical cord-matched quantitative MRI study.

BACKGROUND: We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability. METHODS: A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord-matched protocol with brain-and-cord-unified imaging readouts. Lesion and NA-tissue volumes and qMRI metrics reflecting demyelination and axonal loss were obtained. Random forest analyses identified the most relevant volumetric/qMRI measures to clinical outcomes. Confounder-adjusted linear regression estimated the actual MRI-clinical associations. RESULTS: Several qMRI/volumetric differences between patients and controls were observed (p < 0.01). Higher NA-deep grey matter quantitative-T1 (EDSS: beta = 7.96, p = 0.006; 9HPT: beta = -0.09, p = 0.004), higher NA-white matter orientation dispersion index (TWT: beta = -3.21, p = 0.005; SDMT: beta = -847.10, p < 0.001), lower whole-cord bound pool fraction (9HPT: beta = 0.79, p = 0.001) and higher NA-cortical grey matter quantitative-T1 (SDMT = -94.31, p < 0.001) emerged as particularly relevant predictors of greater disability. CONCLUSION: Fast brain-and-cord-matched qMRI protocols are feasible and identify demyelination - combined with other mechanisms - as key for disability accumulation in PMS.

Bioinformatics analyses of gene expression profile to identify pathogenic mechanisms for COVID-19 infection and cutaneous lupus erythematosus.

Objective: The global mortality rates have surged due to the ongoing coronavirus disease 2019 (COVID-19), leading to a worldwide catastrophe. Increasing incidents of patients suffering from cutaneous lupus erythematosus (CLE) exacerbations after either contracting COVID-19 or getting immunized against it, have been observed in recent research. However, the precise intricacies that prompt this unexpected complication are yet to be fully elucidated. This investigation seeks to probe into the molecular events inciting this adverse outcome. Method: Gene expression patterns from the Gene Expression Omnibus (GEO) database, specifically GSE171110 and GSE109248, were extracted. We then discovered common differentially expressed genes (DEGs) in both COVID-19 and CLE. This led to the creation of functional annotations, formation of a protein-protein interaction (PPI) network, and identification of key genes. Furthermore, regulatory networks relating to these shared DEGs and significant genes were constructed. Result: We identified 214 overlapping DEGs in both COVID-19 and CLE datasets. The following functional enrichment analysis of these DEGs highlighted a significant enrichment in pathways related to virus response and infectious disease in both conditions. Next, a PPI network was constructed using bioinformatics tools, resulting in the identification of 5 hub genes. Finally, essential regulatory networks including transcription factor-gene and miRNA-gene interactions were determined. Conclusion: Our findings demonstrate shared pathogenesis between COVID-19 and CLE, offering potential insights for future mechanistic investigations. And the identification of common pathways and key genes in these conditions may provide novel avenues for research.

Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?

Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant "delta hepatitis", cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).

Pathogenic mechanisms underlying itch in atopic dermatitis: the emerging role of neuroimmune interactions.

Itch is a frequent dermatological sensation that can occur in a variety of skin conditions, including atopic dermatitis, inflammatory disorders characterised by eczematous lesions and chronic itch. The pathogenic mechanisms that lead to itch in atopic dermatitis are not fully understood. The current knowledge of its aetiology highlights the complex interplay among multiple pathogenic factors such as epidermal barrier dysfunction, immune dysregulation, and its interaction with the nervous system. Furthermore, a relationship between itch intensity and certain factors such as stress, sleep disturbance, and pollutant exposure has often been shown in patients with itch. This article reviews the current advances in the processes behind itch signalling from the skin to the nervous system, focusing on atopic dermatitis pathophysiology. Studies investigating the underlying pathogenic mechanisms of atopic dermatitis have shown that itch management at the nervous system level may be sufficient to reduce itch sensation and improve skin lesions.

Taurine, a Component of the Tear Film, Exacerbates the Pathogenic Mechanisms of Acanthamoeba castellanii in the Ex Vivo Amoebic Keratitis Model.

Acanthamoeba spp. is the etiological agent of amoebic keratitis. In this study, the effect of taurine in physiological concentrations in tears (195 µM) on trophozoites of Acanthamoeba castellanii through the ex vivo amoebic keratitis model was evaluated. Trophozoites were coincubated with the Syrian golden hamster cornea (Mesocricetus auratus) for 3 and 6 h. Group 1: Control (-). Corneas coincubated with amoebic culture medium and taurine. Group 2: Control (+). Corneas coincubated with trophozoites without taurine. Group 3: Corneas coincubated with taurine 15 min before adding trophozoites. Group 4: Trophozoites coincubated 15 min with taurine before placing them on the cornea. Group 5: Corneas coincubated for 15 min with trophozoites; subsequently, taurine was added. Results are similar for both times, as evaluated by scanning electron microscopy. As expected, in the corneas of Group 1, no alterations were observed in the corneal epithelium. In the corneas of Group 2, few adhered trophozoites were observed on the corneal surface initiating migrations through cell junctions as previously described; however, in corneas of Groups 3, 4 and 5, abundant trophozoites were observed, penetrating through different corneal cell areas, emitting food cups and destabilizing corneal surface in areas far from cell junctions. Significant differences were confirmed in trophozoites adherence coincubated with taurine (p < 0.05). Taurine does not prevent the adhesion and invasion of the amoebae, nor does it favor its detachment once these have adhered to the cornea, suggesting that taurine in the physiological concentrations found in tears stimulates pathogenic mechanisms of A. castellanii.

Spinocerebellar ataxia type 11 (SCA11): An update.

Spinocerebellar ataxias, also called autosomal dominant cerebellar ataxias, are a group of neurological genetic diseases characterised by chronic, progressive cerebellar ataxia. The clinical hallmark of spinocerebellar ataxia is the loss of balance and coordination, accompanied by slurred speech. Spinocerebellar ataxia type 11 is a rare subtype of spinocerebellar ataxia caused by mutations in the tau tubulin kinase 2 gene. Patients with spinocerebellar ataxia are clinically characterised by slowly progressive cerebellar ataxia, trunk and limb ataxia, and eye movement abnormalities with occasional pyramidal features. Peripheral neuropathy and dystonia are rare. According to the literature, only nine families affected with spinocerebellar ataxia have been reported worldwide. Herein, a series of spinocerebellar ataxia cases are discussed in detail to determine the potential research direction of this dysfunction, including its epidemiology, clinical features, genetic characteristics, diagnosis and differential diagnosis, pathogenic mechanisms, treatment, prognosis, follow-up, genetic counselling and future perspectives, and to improve the overall understanding of spinocerebellar ataxia among clinicians, researchers and patients.

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease.

Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.

Copper in cancer: From pathogenesis to therapy.

One of the basic trace elements for the structure and metabolism of human tissue is copper. However, as a heavy metal, excessive intake or abnormal accumulation of copper in the body can cause inevitable damage to the organism because copper can result in direct injury to various cell components or disruption of the redox balance, eventually leading to cell death. Interestingly, a growing body of research reports that diverse cancers have raised serum and tumor copper levels. Tumor cells depend on more copper for their metabolism than normal cells, and a decrease in copper or copper overload can have a detrimental effect on tumor cells. New modalities for identifying and characterizing copper-dependent signals offer translational opportunities for tumor therapy, but their mechanisms remain unclear. Therefore, this article summarizes what we currently know about the correlation between copper and cancer and describes the characteristics of copper metabolism in tumor cells and the prospective application of copper-derived therapeutics.

Bioinformatics and computational analyses of kidney stone modulatory proteins lead to solid experimental evidence and therapeutic potential.

In recent biomedical research, bioinformatics and computational analyses have played essential roles for examining experimental findings and database information. Several bioinformatic tools have been developed and made publicly available for analyzing protein sequence, structure, functional motif/domain, and interactions network. Such properties are very helpful to define biochemical and functional roles of the protein(s) of interest. During the past few decades, bioinformatics and computational biotechnology have been widely applied to kidney stone research. This review summarizes commonly used tools and evidence of bioinformatics and computational biotechnology applied to kidney stone disease (KSD) with special emphasis on analyses of the stone modulatory proteins that play critical roles in kidney stone formation. Such analyses lead to solid experimental evidence to demonstrate mechanisms underlying their stone modulatory activities. The findings obtained from such analyses may also lead to better understanding of KSD pathogenesis and to further development of new therapeutic and preventive strategies.

Persistent and Severe Viral Replication in PBMCs with Moderate Immunosuppression Served an Alternative Novel Pathogenic Mechanism for Canine Morbillivirus.

Measles virus and canine distemper virus (CDV) cause lethal infections in their respective hosts characterized by severe immunosuppression. To furtherly acknowledge the attenuated mechanisms of the regionally ongoing epidemic CDV isolates and provide novel perspectives for designing new vaccines and therapeutic drugs, a recombinant CDV rHBF-vacH was employed with a vaccine hemagglutinin (H) gene replacement by reverse genetics based on an infectious cDNA clone for the CDV wild-type HBF-1 strain. Interestingly, unlike previously published reports that a vaccine H protein completely changed a pathogenic wild-type CDV variant to be avirulent, rHBF-vacH was only partially attenuated by alleviating the degree of viral immunosuppression, and still caused 66.7% lethality in ferrets with a prolonged period of disease. Further comparisons of pathogenic mechanisms proved that the weaker but necessary invasions into peripheral blood mononuclear cells (PBMCs) of rHBF-vacH, and subsequently persistent viral replications in PBMCs and multiple organs, together contributed to its 66.7% mortality. In addition, despite significantly higher titers than the parent viruses, rHBF-vacH would not be a suitable candidate for a live vaccine, with great invasion and infection potentials of PBMCs from 16 tested kinds of host species. Altogether, sustained and severe viral replication in PBMCs with moderate immunosuppression was first proven to be an alternative novel pathogenic mechanism for CDV, which might help us to understand possible reasons for CDV fatal infections among domestic dogs and the highly susceptible wild species during natural transmission. IMPORTANCE Despite widespread vaccine campaigns for domestic dogs, CDV remained an important infectious disease in vaccinated carnivores and wild species. In recent years, the regionally ongoing epidemic CDV isolates have emphasized conservation threats to, and potentially disastrous epidemics in, endangered species worldwide. However, little is known about how to deal with the CDV variants constantly regional epidemic. In this study, we employed a recombinant CDV rHBF-vacH with a vaccine H gene replacement in a CDV wild-type HBF-1 context to attenuate the epidemic CDV variant to design a new vaccine candidate. Interestingly, rHBF-vacH was only partially attenuated by alleviating the degree of viral immunosuppression, and still caused 66.7% lethality in ferrets by weaker but necessary invasions into PBMCs, and subsequently persistent and severe viral replications in PBMCs. Significantly higher virus titers of rHBF-vacH in vitro might indicate the rapid cell-to-cell spreads in vivo that indirectly contribute to fatal infections of rHBF-vacH in ferrets.

New target DDR1: A "double-edged sword" in solid tumors.

Globally, cancer is a major catastrophic disease that seriously threatens human health. Thus, there is an urgent need to find new strategies to treat cancer. Among them, identifying new targets is one of the best ways to treat cancer at present. Especially in recent years, scientists have discovered many new targets and made breakthroughs in the treatment of cancer, bringing new hope to cancer patients. As one of the novel targets for cancer treatment, DDR1 has attracted much attention due to its unique role in cancer. Hence, here, we focus on a new target, DDR1, which may be a "double-edged sword" of human solid tumors. In this review, we provide a comprehensive overview of how DDR1 acts as a "double-edged sword" in cancer. First, we briefly introduce the structure and normal physiological function of DDR1; Second, we delineate the DDR1 expression pattern in single cells; Next, we sorte out the relationship between DDR1 and cancer, including the abnormal expression of DDR1 in cancer, the mechanism of DDR1 and cancer occurrence, and the value of DDR1 on cancer prognosis. In addition, we introduced the current status of global drug and antibody research and development targeting DDR1 and its future design prospects; Finally, we summarize and look forward to designing more DDR1-targeting drugs in the future to make further progress in the treatment of solid tumors.

How the Immune System Responds to Allergy Immunotherapy.

IgE-mediated diseases represent a highly diversified and multifactorial group of disorders that can deeply impact the patients' quality of life. Currently, allergy immunotherapy (AIT) still remains the gold standard for the management of such pathologies. In this review, we comprehensively examine and discuss how AIT can affect both the innate and the adaptive immune responses at different cell levels and propose timing-scheduled alterations induced by AIT by hypothesizing five sequential phases: after the desensitization of effector non-lymphoid cells and a transient increase of IgE (phase 1), high doses of allergen given by AIT stimulate the shift from type 2/type 3 towards type 1 response (phase 2), which is progressively potentiated by the increase of IFN-γ that promotes the chronic activation of APCs, progressively leading to the hyperexpression of Notch1L (Delta4) and the secretion of IL-12 and IL-27, which are essential to activate IL-10 gene in Th1 and ILC1 cells. As consequence, an expansion of circulating memory Th1/Tr1 cells and ILC-reg characterizes the third phase addressed to antagonize/balance the excess of type 1 response (phase 3). The progressive increase of IL-10 triggers a number of regulatory circuits sustained by innate and adaptive immune cells and favoring T-cell tolerance (phase 4), which may also be maintained for a long period after AIT interruption (phase 5). Different administration approaches of AIT have shown a similar tailoring of the immune responses and can be monitored by timely, optimized biomarkers. The clinical failure of this treatment can occur, and many genetic/epigenetic polymorphisms/mutations involving several immunological mechanisms, such as the plasticity of immune responses and the induction/maintenance of regulatory circuits, have been described. The knowledge of how AIT can shape the immune system and its responses is a key tool to develop novel AIT strategies including the engineering of allergen or their epitopes. We now have the potential to understand the precise causes of AIT failure and to establish the best biomarkers of AIT efficacy in each phase of the treatment.

Advances in lipodystrophy syndrome caused by LMNA gene mutation.

Lipodystrophy syndrome caused by LMNA gene mutation is a group of autosomal dominant monogenic diseases, characterized by selective fat loss and metabolic abnormalities with insulin resistance. In this review, we summarize the clinical manifestations caused by multiple pathogenic LMNA mutations reported so far, including metabolic complications, cardiovascular abnormalities, gonadal axis disorders, myopathy, and renal abnormalities. Meanwhile, we also clarify the possible pathogenic mechanism, diagnosis, and treatment, in order to improve the understanding of the disease and to provide a reference for basic research and clinical diagnosis and treatment of this disease.

DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets.

BACKGROUND: Diabetic retinopathy (DR), a specific neuron-vascular complication of diabetes, is a major cause of vision loss among middle-aged people worldwide, and the number of DR patients will increase with the increasing incidence of diabetes. At present, it is limited in difficult detection in the early stages, limited treatment and unsatisfactory treatment effects in the advanced stages. MAIN BODY: The pathogenesis of DR is complicated and involves epigenetic modifications, oxidative stress, inflammation and neovascularization. These factors influence each other and jointly promote the development of DR. DNA methylation is the most studied epigenetic modification, which has been a key role in the regulation of gene expression and the occurrence and development of DR. Thus, this review investigates the relationship between DNA methylation and other complex pathological processes in the development of DR. From the perspective of DNA methylation, this review provides basic insights into potential biomarkers for diagnosis, preventable risk factors, and novel targets for treatment. CONCLUSION: DNA methylation plays an indispensable role in DR and may serve as a prospective biomarker of this blinding disease in its relatively early stages. In combination with inhibitors of DNA methyltransferases can be a potential approach to delay or even prevent patients from getting advanced stages of DR.

Acanthamoeba castellanii: Effect of neuroactive substances on trophozoite migration.

Acanthamoeba castellanii is the etiological agent of granulomatous amebic encephalitis, amebic keratitis, and skin lesions. In vitro and in vivo studies have demonstrated that Acanthamoeba trophozoites induce contact-dependent, and contact-independent pathogenic mechanisms. We have explored the potential role neuroactive substances may have in the migration of Acanthamoeba castellanii trophozoites using Transwell permeable supports in the presence of physiological concentrations of dopamine, glutamate, serotonin, or taurine diluted in PBS. Quantitation of migrated amoebae was carried out in scanning electron micrographs of the upper and under compartments sides of the chamber membranes. Our results showed that at 2 h of interaction, a statistically significant larger proportion of A. castellanii trophozoites migrated through the chamber membranes when neurotransmitters were placed in the lower compartments of the chambers compared to control. This migration effect was more evident under the presence of glutamate and taurine on the three surfaces (upper/lower membrane and bottom compartment) when the percentage of migrated trophozoites was analyzed. Scanning electron microscopy of trophozoites revealed that glutamate and taurine induced the formation of large adhesion lamellas and phagocytic stomas. These observations suggest that certain neuroactive substances could stimulate the migration of A. castellanii trophozoites in the central nervous system.

A Bursaphelenchus xylophilus pathogenic protein Bx-FAR-1, as potential control target, mediates the jasmonic acid pathway in pines.

BACKGROUND: The pine wilt disease (PWD) caused by Bursaphelenchus xylophilus is a devastating forest disease and its pathogenesis remains unclear. Secreted enzymes and proteins are important pathogenicity determinants and Bx-FAR-1 is an important pathogenic protein involved in the interaction between pine and B. xylophilus. However, the function of the Bx-FAR-1 protein in monitoring and prevention PWD remains unknown. RESULTS: We found a small peptide of B. xylophilus effector Bx-FAR-1 is sufficient for immunosuppression function in Nicotiana benthamiana. Transient expression of Bx-FAR-1 in N. benthamiana revealed that nuclear localization is required for its function. The results of the ligand binding test showed that Bx-FAR-1 protein had the ability to bind fatty acid and retinol. We demonstrated that Bx-FAR-1 targeted to the nuclei of Pinus thunbergii using the polyclonal antibody by immunologic approach. The content of jasmonic acid (JA) was significantly increased in P. thunbergii infected with B. xylophilus when Bx-FAR-1 was silenced. We identified an F-box protein as the host target of Bx-FAR-1 by yeast two-hybrid and co-immunoprecipitation. Moreover, we found that Pt-F-box-1 was up-regulated during B. xylophilus infection and the expression of Pt-F-box-1 was increased in Bx-FAR-1 double-stranded RNA (dsRNA)-treated host pines. CONCLUSION: This study illustrated that Bx-FAR-1 might mediate the JA pathway to destroy the immune system of P. thunbergii, indicating that PWN likely secretes effectors to facilitate parasitism and promote infection, which could better reveal the pathogenesis mechanisms of B. xylophilus and would be beneficial for developing disease control strategies.

Pathological Connections between Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease.

Background: Nonalcoholic fatty liver disease and chronic kidney disease are major public health issues worldwide. The clinical burden of nonalcoholic fatty liver disease is not only confined to liver-related morbidity and mortality, but it also includes the burden of chronic extrahepatic complications. It is well known that liver and kidney are strictly interconnected in physiological and pathological conditions. Summary: Mounting evidence indicates a strong association between nonalcoholic fatty liver disease and chronic kidney disease, independent of the identified cardiorenal risk factors. The presence and severity of nonalcoholic fatty liver disease are related to the developmental stage and risk of chronic kidney disease. And chronic kidney disease progression also contributes to nonalcoholic fatty liver disease development. Nonalcoholic fatty liver disease and chronic kidney disease mutually contribute to disease progression through pathological links. Shared pathogenic mechanisms also exist between nonalcoholic fatty liver disease and chronic kidney disease, including pyroptosis and ferroptosis. Additionally, the use of combined liver-kidney transplantation has increased exponentially in recent years. Key Messages: This review focuses on the emerging pathological mechanisms linking nonalcoholic fatty liver disease and chronic kidney disease and shared pathogenic mechanisms to find novel targeted therapies and retard the progression of both disease processes.

Features of Pathobiology and Clinical Translation of Approved Treatments for Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last 2 years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, which is another factor. SUMMARY: In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. KEY MESSAGES: We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.