Gut Dysbiosis during COVID-19 and Potential Effect of Probiotics

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus of the family Coronaviridae, causes coronavirus disease 2019 (COVID-19), an influenza-like disease that chiefly infects the lungs through respiratory transmission. The spike protein of SARS-CoV-2, a transmembrane protein in its outer portion, targets angiotensin-converting enzyme 2 (ACE2) as the binding receptor for the cell entry. As ACE2 is highly expressed in the gut and pulmonary tissues, SARS-CoV-2 infections frequently result in gastrointestinal inflammation, with presentations ordinarily ranging from intestinal cramps to complications with intestinal perforations. However, the evidence detailing successful therapy for gastrointestinal involvement in COVID-19 patients is currently limited. A significant change in fecal microbiomes, namely dysbiosis, was characterized by the enrichment of opportunistic pathogens and the depletion of beneficial commensals and their crucial association to COVID-19 severity has been evidenced. Oral probiotics had been evidenced to improve gut health in achieving homeostasis by exhibiting their antiviral effects via the gut–lung axis. Although numerous commercial probiotics have been effective against coronavirus, their efficacies in treating COVID-19 patients remain debated. In ClinicalTrials.gov, 19 clinical trials regarding the dietary supplement of probiotics, in terms of Lactobacillus and mixtures of Bifidobacteria and Lactobacillus, for treating COVID-19 cases are ongoing. Accordingly, the preventive or therapeutic role of probiotics for COVID-19 patients can be elucidated in the near future.

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The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

AJP Renal Physiology ◽

10.1152/ajprenal.00059.2021 ◽

2021 ◽

Author(s):

Diana Hamdan ◽

Lisa A. Robinson

Keyword(s):

Therapeutic Potential ◽

Kidney Diseases ◽

Transmembrane Protein ◽

Soluble Form ◽

Protective Effects ◽

Chronic Kidney Diseases ◽

The Family ◽

Soluble Species ◽

And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

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ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19

Clinical Science ◽

10.1042/cs20200486 ◽

2020 ◽

Vol 134 (22) ◽

pp. 3047-3062

Author(s):

Koichi Yamamoto ◽

Hikari Takeshita ◽

Hiromi Rakugi

Keyword(s):

Skeletal Muscle ◽

Transmembrane Protein ◽

Renin Angiotensin System ◽

Protective Role ◽

Potential Contribution ◽

Angiotensin Converting Enzyme 2 ◽

Multiple Organs ◽

Potential Association ◽

Entry Receptor

Abstract Angiotensin converting enzyme-2 (ACE2) is a multifunctional transmembrane protein recently recognised as the entry receptor of the virus causing COVID-19. In the renin–angiotensin system (RAS), ACE2 cleaves angiotensin II (Ang II) into angiotensin 1-7 (Ang 1-7), which is considered to exert cellular responses to counteract the activation of the RAS primarily through a receptor, Mas, in multiple organs including skeletal muscle. Previous studies have provided abundant evidence suggesting that Ang 1-7 modulates multiple signalling pathways leading to protection from pathological muscle remodelling and muscle insulin resistance. In contrast, there is relatively little evidence to support the protective role of ACE2 in skeletal muscle. The potential contribution of endogenous ACE2 to the regulation of Ang 1-7-mediated protection of these muscle pathologies is discussed in this review. Recent studies have suggested that ACE2 protects against ageing-associated muscle wasting (sarcopenia) through its function to modulate molecules outside of the RAS. Thus, the potential association of sarcopenia with ACE2 and the associated molecules outside of RAS is also presented herein. Further, we introduce the transcriptional regulation of muscle ACE2 by drugs or exercise, and briefly discuss the potential role of ACE2 in the development of COVID-19.

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A review of the reasons for high prevalence and rapid progression of COVID-19 in men

Journal of Preventive Epidemiology ◽

10.34172/jpe.2022.03 ◽

2021 ◽

Vol 7 (1) ◽

pp. e03-e03

Author(s):

Neda Taghizabet ◽

Fatemeh Rezaei-Tazangi ◽

Hossein Roghani‐Shahraki

Keyword(s):

Transmembrane Protein ◽

Rapid Progression ◽

Acute Type ◽

Converting Enzyme ◽

Immune Functions ◽

Male And Female ◽

Angiotensin Converting Enzyme 2 ◽

High Prevalence ◽

Hormonal Levels

Previous studies have demonstrated a relationship between gender and COVID-19 outcomes. In addition, this is confirmed that men have more danger of progressing an acute type of the illness than women, specifies the significance of miscellaneous data related to male and female patients with COVID-19. In other words, some factors like hormonal levels and immune function may interact with each other. A perception of the fundamental reasons for gender diversities in COVID-19 patients can beget a chance for disease prevention and faster treatment. The present study evaluates the role of gender in the incidence and progression of the COVID-19 disease. It has been explained that how gender affects angiotensin-converting enzyme 2 (ACE2), which is a basic factor for the COVID-19 pathogenesis introducing the sex diversities in platelet function, immune reactions and how sex hormones affect immune functions, also the effect of androgens on transmembrane protein serine protease 2 (TMPRSS2) receptor in COVID-19 patients was investigated.

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Coxsackievirus infection induces a non-canonical autophagy independent of the ULK and PI3K complexes

Scientific Reports ◽

10.1038/s41598-020-76227-7 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Yasir Mohamud ◽

Junyan Shi ◽

Hui Tang ◽

Pinhao Xiang ◽

Yuan Chao Xue ◽

...

Keyword(s):

Rna Virus ◽

Transmembrane Protein ◽

Kinase Domain ◽

Conjugation System ◽

Culture Cells ◽

Cvb3 Infection ◽

Cellular Machinery ◽

Autophagy Pathway ◽

Substrate Binding Domain

Abstract Coxsackievirus B3 (CVB3) is a single-stranded positive RNA virus that usurps cellular machinery, including the evolutionarily anti-viral autophagy pathway, for productive infections. Despite the emergence of double-membraned autophagosome-like vesicles during CVB3 infection, very little is known about the mechanism of autophagy initiation. In this study, we investigated the role of established autophagy factors in the initiation of CVB3-induced autophagy. Using siRNA-mediated gene-silencing and CRISPR-Cas9-based gene-editing in culture cells, we discovered that CVB3 bypasses the ULK1/2 and PI3K complexes to trigger autophagy. Moreover, we found that CVB3-induced LC3 lipidation occurred independent of WIPI2 and the transmembrane protein ATG9 but required components of the late-stage ubiquitin-like ATG conjugation system including ATG5 and ATG16L1. Remarkably, we showed the canonical autophagy factor ULK1 was cleaved through the catalytic activity of the viral proteinase 3C. Mutagenesis experiments identified the cleavage site of ULK1 after Q524, which separates its N-terminal kinase domain from C-terminal substrate binding domain. Finally, we uncovered PI4KIIIβ (a PI4P kinase), but not PI3P or PI5P kinases as requisites for CVB3-induced LC3 lipidation. Taken together, our studies reveal that CVB3 initiates a non-canonical form of autophagy that bypasses ULK1/2 and PI3K signaling pathways to ultimately converge on PI4KIIIβ- and ATG5–ATG12–ATG16L1 machinery.

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CORONAVIRUS: Pathology, Immunology and Therapies.

10.46940/ijpi.01.1002 ◽

2020 ◽

pp. 1-17

Keyword(s):

Immune System ◽

Virus Infection ◽

Severe Acute Respiratory Syndrome ◽

Effective Treatment ◽

Common Cold ◽

Rna Virus ◽

Clinical Protocols ◽

Biochemical Mechanism ◽

The Family

Abstract Coronavirus is a family of positive single-stranded RNA virus belonging to the family of coronaviridae. Coronavirus-19 infection (COVID-19) has appeared in 2019 and so there is no effective treatment that can eradicate it. The objective of this review is to present data on cellular and molecular characteristic of virus infection and also elucidate all molecular associated events with covid-19 infection in patients. The infection in humans can cause diseases ranging from a common cold to more serious diseases such as severe acute respiratory syndrome (SARS). The disease that it transmits (Covid-19) cannot be cured with conventional treatments. However, a large number of protocols have been implemented based on the sequels that it produces. In this review we summarize 1) the role of immune system against this pathogen as well as the biochemical mechanism by which squealed is responsible for disease progression 2) the possibility or not that patients who have suffered the disease have antibodies against the virus and 3) the clinical protocols used in order to mitigate induced-damage by virus.

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Do anti-androgens have potential as therapeutics for COVID-19?

Endocrinology ◽

10.1210/endocr/bqab114 ◽

2021 ◽

Author(s):

Franck Mauvais-Jarvis

Keyword(s):

Transmembrane Protein ◽

Mortality Rates ◽

Potential Effect ◽

Gender Disparity ◽

Spike Protein ◽

Protein Cleavage ◽

Prostate Cancer Cells ◽

Future Directions ◽

Angiotensin Converting Enzyme 2 ◽

Male Patients

Abstract COVID-19 is characterized by a gender disparity in severity, with men exhibiting higher hospitalization and mortality rates than women. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, infects cells following recognition and attachment of the viral spike (S) glycoprotein to the angiotensin-converting enzyme 2 (ACE2) transmembrane protein, followed by spike protein cleavage and activation by cell surface transmembrane protease serine 2 (TMPRSS2). In prostate cancer cells, androgen acting on the androgen receptor (AR) increases TMPRSS2 expression, which has led to the hypothesis that androgen-dependent expression of TMPRSS2 in the lung, may increase men’s susceptibility to severe COVID-19 and that, accordingly, suppressing androgen production or action may mitigate COVID-19 severity by reducing SARS-CoV-2 amplification. Several ongoing clinical trials are testing the ability of androgen deprivation therapies (ADT) or anti-androgens to mitigate COVID-19.This perspective discusses clinical and molecular advances on the rapidly evolving field of AR action on TMPRSS2 expression and SARS-COV-2 infection, and the potential effect of anti-androgens on COVID-19 severity in male patients. It discusses limitations of current studies and offer insight for future directions.

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Role of Endolysosomes in Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Coronavirus Disease 2019 Pathogenesis: Implications for Potential Treatments

Frontiers in Pharmacology ◽

10.3389/fphar.2020.595888 ◽

2020 ◽

Vol 11 ◽

Author(s):

Nabab Khan ◽

Xuesong Chen ◽

Jonathan D. Geiger

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Rna Virus ◽

Therapeutic Strategies ◽

Host Protein ◽

Focus Attention ◽

Angiotensin Converting Enzyme 2 ◽

Immunological Responses ◽

Endocytic Machinery ◽

Replication Sites

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an enveloped, single-stranded RNA virus. Humans infected with SARS-CoV-2 develop a disease known as coronavirus disease 2019 (COVID-19) with symptoms and consequences including acute respiratory distress syndrome (ARDS), cardiovascular disorders, and death. SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2). The process of virus entry into endosomes and its release from endolysosomes are key features of enveloped viruses. Thus, it is important to focus attention on the role of endolysosomes in SARS-CoV-2 infection. Indeed, coronaviruses are now known to hijack endocytic machinery to enter cells such that they can deliver their genome at replication sites without initiating host detection and immunological responses. Hence, endolysosomes might be good targets for developing therapeutic strategies against coronaviruses. Here, we focus attention on the involvement of endolysosomes in SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we explore endolysosome-based therapeutic strategies to restrict SARS-CoV-2 infection and COVID-19 pathogenesis.

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Identification and Characterization of a Novel Emaravirus From Grapevine Showing Chlorotic Mottling Symptoms

Frontiers in Microbiology ◽

10.3389/fmicb.2021.694601 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xudong Fan ◽

Chen Li ◽

Zunping Zhang ◽

Fang Ren ◽

Guojun Hu ◽

...

Keyword(s):

Phylogenetic Trees ◽

High Throughput Sequencing ◽

Rna Virus ◽

Reading Frame ◽

A Genome ◽

The Family ◽

Pcr Products ◽

Chlorotic Mottling

A novel negative-sense, single-stranded (ss) RNA virus was identified in a “Shennong Jinhuanghou” (SJ) grapevine showing severe chlorotic mottling symptoms by integrating high-throughput sequencing (HTS) and conventional Sanger sequencing of reverse transcription polymerase chain reaction (RT-PCR) products. The virus was provisionally named as “grapevine emaravirus A” (GEVA). GEVA had a genome comprising five genomic RNA segments, each containing a single open reading frame on the viral complementary strand and two untranslated regions with complementary 13- nt stretches at the 5′ and 3′ terminal ends. RNA1 (7,090 nt), RNA2 (2,097 nt), RNA3 (1,615 nt), and RNA4 (1,640 nt) encoded putative proteins P1–P4 that, based on their conserved motifs, were identified as the RNA-dependent RNA polymerase, glycoprotein, nucleocapsid protein, and movement protein, respectively. However, the functional role of protein P5 encoded by RNA5 (1,308 nt) could not be determined. Phylogenetic trees constructed based on amino acids of P1 to P4, allocated GEVA in clade I, together with other species-related emaraviruses. These data support the proposal that GEVA is a representative member of a novel species in the genus Emaravirus of the family Fimoviridae. Moreover, when GEVA was graft-transmitted to SJ and “Beta” grapevines, all grafted plants showed the same symptoms, similar to those observed in the source of the inoculum. This is the first report to our knowledge of an emaravirus infecting grapevine and its possible association with chlorotic mottling symptoms.

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Repurposing of chloroquine and hydroxychloroquine for the management of COVID-19

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20210561 ◽

2021 ◽

Vol 10 (3) ◽

pp. 300

Author(s):

Fidelis A. Gberindyer ◽

Felix K. Shima ◽

Joel A. Bosha ◽

Victor M. Ahur ◽

Festus T. Swem ◽

...

Keyword(s):

Viral Infections ◽

Antiviral Effect ◽

Economic Activities ◽

Clinical Safety ◽

Transmembrane Receptors ◽

Angiotensin Converting Enzyme 2 ◽

Lysosomal Ph ◽

Life Threatening ◽

Near Future

The Coronavirus Disease-19 (COVID-19) pandemic has impacted adversely on the global health and socio-economic activities. There is currently no evidence-based anti-SARS-CoV-2 drug for COVID-19 therapy. This review highlights some pharmacological properties of chloroquine and hydroxychloroquine and prospects of repurposing them for the treatment of COVID-19. Google scholar was employed in searching relevant published journal articles (n=118) in English. The search was later narrowed down to SARS-CoV-2, pathophysiology of COVID-19, available drugs for the management of COVID-19, clinical trials on repurposing drugs for COVID-19 therapy, and the role of chloroquine and hydroxychloroquine in the treatment of COVID-19. Documented evidence revealed that chloroquine and hydroxychloroquine have antiviral and immune-modulatory properties. Their antiviral effect is due to inhibition of the spike proteins of SARS-CoV-2 from binding to the cellular transmembrane receptors, angiotensin converting enzyme-2 thereby preventing viral infections. Also, sequestration of these drugs into the lysosomes elevates lysosomal pH thus inhibiting lysosomal enzymatic functions vital for viral replication in those cells. Whereas, their immune-modulatory activity averts the inflammatory complications of COVID-19, particularly acute respiratory syndrome, by preventing cytokine storm through suppression of the production and putative release of pro-inflammatory cytokines. The adverse effects from these drugs, notably irreversible retinopathy and cardiac arrhythmia are rare but become life-threatening when they occur. These are minimal with hydroxychloroquine compared to chloroquine. Chloroquine and hydroxychloroquine could be repurposed for managing COVID-19 cases because they are already extensively used for treating acute nonresistant malaria and auto-immune diseases. Also, a viable vaccine cannot be available in the near future while there is a pressing need for treatments to lower the daily rise in morbidity and mortality associated with the disease. Nevertheless, we suggest that emphasis should be on hydroxychloroquine because of its superior antiviral effect and clinical safety.

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The Chemokine Systems at the Crossroads of Inflammation and Energy Metabolism in the Development of Obesity

International Journal of Molecular Sciences ◽

10.3390/ijms222413528 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13528

Author(s):

Pei-Chi Chan ◽

Po-Shiuan Hsieh

Keyword(s):

Energy Metabolism ◽

Chemokine Receptors ◽

Metabolic Disorders ◽

Molecular Mechanisms ◽

Potential Effect ◽

Post Translational Modification ◽

Chronic Complications ◽

Inflammatory Milieu ◽

Near Future

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue accompanied with alterations in the immune and metabolic responses. Although the chemokine systems have been documented to be involved in the control of tissue inflammation and metabolism, the dual role of chemokines and chemokine receptors in the pathogenesis of the inflammatory milieu and dysregulated energy metabolism in obesity remains elusive. The objective of this review is to present an update on the link between chemokines and obesity-related inflammation and metabolism dysregulation under the light of recent knowledge, which may present important therapeutic targets that could control obesity-associated immune and metabolic disorders and chronic complications in the near future. In addition, the cellular and molecular mechanisms of chemokines and chemokine receptors including the potential effect of post-translational modification of chemokines in the regulation of inflammation and energy metabolism will be discussed in this review.

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