scholarly journals December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

2021 ◽  
Vol 23 (6) ◽  
pp. 151-154
Author(s):  
Richard Robbins ◽  
◽  
Stephen Klotz
Keyword(s):  
Interstitial Lung Disease ◽  
Inpatient Care ◽  
Rna Viruses ◽  
Specific Binding ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
A Cell ◽  
Coronavirus Infection

No abstract available. Article truncated after 150 words. We thought a follow-up to our original brief review of COVID-19 in February, 2020 might be useful. As we write this in early December 2021, we again caution that this area is rapidly changing and what is true today will likely be outdated tomorrow. We again borrowed heavily from the Centers for Disease Control (CDC) CDC website and the NIH website which have extensive discussions over numerous pages covering COVID-19. Our hope is to condense those recommendations. We do not discuss inpatient care in any detail. COVID-19 Variants The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors which are normally on a cell. These include human aminopeptidase N (APN; HCoV-229E), angiotensin-converting enzyme 2 (ACE2; HCoV-NL63, SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase 4 (DPP4; MERS-CoV). All viruses, but especially simple single-stranded RNA viruses like COVID-19, constantly change through mutation …

scholarly journals Plasma From Recovered COVID-19 Patients Inhibits Spike Protein Binding to ACE2 in a Microsphere-Based Inhibition Assay

2020 ◽  
Vol 222 (12) ◽  
pp. 1965-1973 ◽  
Author(s):  
Edward P Gniffke ◽  
Whitney E Harrington ◽  
Nicholas Dambrauskas ◽  
Yonghou Jiang ◽  
Olesya Trakhimets ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Angiotensin Converting Enzyme ◽  
Protein Binding ◽  
Immunoglobulin G ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Inhibition Assay ◽  
Flow Cytometry Assay ◽  
Angiotensin Converting Enzyme 2 ◽  
A Cell

Abstract We present a microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to angiotensin-converting enzyme 2. Plasma from 22 patients who had recovered from mild coronavirus disease 2019 (COVID-19) and expressed anti–spike protein trimer immunoglobulin G inhibited angiotensin-converting enzyme 2–spike protein binding to a greater degree than controls. The degree of inhibition was correlated with anti–spike protein immunoglobulin G levels, neutralizing titers in a pseudotyped lentiviral assay, and the presence of fever during illness. This inhibition assay may be broadly useful to quantify the functional antibody response of patients recovered from COVID-19 or vaccine recipients in a cell-free assay system.

scholarly journals Increasing Host Cellular Receptor—Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection

2020 ◽  
Author(s):  
Pei-Hui Wang ◽  
Yun Cheng
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Emerging Infectious Diseases ◽  
Cell Receptor ◽  
Host Cells ◽  
Cellular Receptor ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Coronavirus Infection ◽  
Entry Receptor

AbstractThe ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins of 2019-nCoV and SARS-CoV may use the same host cell receptor called angiotensin-converting enzyme 2 (ACE2) for entering into host cells. The affinity between ACE2 and 2019-nCoV S is much higher than ACE2 binding to SARS-CoV S protein, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 can be significantly upregulated after infection of various viruses including SARS-CoV and MERS-CoV. Basing on findings here, we propose that coronavirus infection can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 expression may be prepared for the future emerging infectious diseases caused by this cluster of viruses.

scholarly journals Can Levamisole be used in the treatment of COVID-19 patients presenting with diarrhea?

2020 ◽  
Vol 14 (08) ◽  
pp. 844-846
Author(s):  
Oğuz Abdullah Uyaroğlu ◽  
Gülay Sain Güven ◽  
İbrahim Güllü
Keyword(s):  
Antiviral Drug ◽  
Cell Receptor ◽  
Host Cells ◽  
Converting Enzyme ◽  
Immunomodulatory Effects ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
The World ◽  
Glandular Cells ◽  
A Cell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China, on Jan 7, 2020. Over the following months, the virus rapidly spread throughout the world. Coronavirus Disease 2019 (COVID-19) can involve the gastrointestinal tract, including symptoms like nausea, vomiting and diarrhea and shedding of the SARS-CoV-2 in feces. Angiotensin-converting enzyme 2 (ACE2) protein, which has been proven to be a cell receptor for SARS-CoV-2, is expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells. According to the literature, rates of COVID-19 patients reporting diarrhea were between 7 - 14%. Diarrhea in the course of COVID-19 disease can cause dehydration and hospitalization. Although no antiviral drug was specifically designed for the treatment of diarrhea, several molecules could have beneficial effects by reducing viral replication. In this letter, we discussed the Levamisole, which is an anthelmintic agent with immunomodulatory effects, could be used effectively both for antiviral therapy and especially in COVID-19 patients with diarrhea.

scholarly journals Comparison of the COVID-2019 (SARS-CoV-2) pathogenesis with SARS-CoV and MERS-CoV infections

2020 ◽  
Vol 15 (5) ◽  
pp. 317-323 ◽  
Author(s):  
Mona Fani ◽  
Ali Teimoori ◽  
Shokouh Ghafari
Keyword(s):  
Small Intestine ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Target Cells ◽  
Specific Drug ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapy Options ◽  
Coronavirus Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in several patients who traveled to Wuhan or went to a seafood wholesale market in Wuhan. The phylogenetic tree showed that SARS-CoV-2 was 96.2% identical to bat β-coronaviruses from lineage B. Also, several studies reported that SARS-CoV-2 uses the SARS-CoV receptor, angiotensin-converting enzyme 2, for entry to target cells. Lung alveolar and small intestine are potential targets for SARS-CoV-2 due to the high expression of the angiotensin-converting enzyme 2 receptor. In this review, we focused on the zoonotic β-coronaviruses and given there is no specific drug or vaccine for coronavirus disease 2019, we reviewed the literature on the therapy options for SARS and Middle East respiratory syndrome coronavirus infection, in order to discover their possible use in the treatment of SARS-CoV-2 infections.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor

2006 ◽  
Vol 81 (3) ◽  
pp. 1162-1173 ◽  
Author(s):  
Chien-Te K. Tseng ◽  
Cheng Huang ◽  
Patrick Newman ◽  
Nan Wang ◽  
Krishna Narayanan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Severe Acute Respiratory Syndrome ◽  
Transgenic Mice ◽  
Angiotensin Converting Enzyme ◽  
Virus Replication ◽  
Clinical Manifestations ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Coronavirus Infection

ABSTRACT Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg+) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg−) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg+ mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg+ AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.

scholarly journals Coronavirus Infections and Type 2 Diabetes—Shared Pathways with Therapeutic Implications

2020 ◽  
Vol 41 (3) ◽  
pp. 457-470 ◽  
Author(s):  
Daniel J Drucker
Keyword(s):  
Type 2 Diabetes ◽  
Viral Infections ◽  
Biological Activities ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Therapeutic Implications ◽  
Increased Risk ◽  
Coronavirus Infection ◽  
Coronavirus Infections

Abstract Abstract Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with type 2 diabetes (T2D). Two coronavirus receptor proteins, angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here, we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.

scholarly journals Species-specific inhibitor sensitivity of angiotensin-converting enzyme 2 (ACE2) and its implication for ACE2 activity assays

2011 ◽  
Vol 301 (5) ◽  
pp. R1293-R1299 ◽  
Author(s):  
Kim Brint Pedersen ◽  
Srinivas Sriramula ◽  
Kavaljit H. Chhabra ◽  
Huijing Xia ◽  
Eric Lazartigues
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Specific Inhibitor ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Experimental Conditions ◽  
Angiotensin Converting Enzyme 2 ◽  
Mouse Tissues ◽  
A Cell ◽  
Species Specific ◽  
Hydrolysis Of

Angiotensin-converting enzyme 2 (ACE2) is a component of the renin-angiotensin system, and its expression and activity have been shown to be reduced in cardiovascular diseases. Enzymatic activity of ACE2 is commonly measured by hydrolysis of quenched fluorescent substrates in the absence or presence of an ACE2-specific inhibitor, such as the commercially available inhibitor DX600. Whereas recombinant human ACE2 is readily detected in mouse tissues using 1 μM DX600 at pH 7.5, the endogenous ACE2 activity in mouse tissues is barely detectable. We compared human, mouse, and rat ACE2 overexpressed in cell lines for their sensitivity to inhibition by DX600. ACE2 from all three species could be inhibited by DX600, but the half maximal inhibitory concentration (IC50) for human ACE2 was much lower (78-fold) than for rodent ACE2. Following optimization of pH, substrate concentration, and antagonist concentration, rat and mouse ACE2 expressed in a cell line could be accurately quantified with 10 μM DX600 (>95% inhibition) but not with 1 μM DX600 (<75% inhibition). Validation that the optimized method robustly quantifies ACE2 in mouse tissues (kidney, brain, heart, and plasma) was performed using wild-type and ACE2 knockout mice. This study provides a reliable method for measuring human, as well as endogenous ACE2 activity in rodents. Our data underscore the importance of validating the effect of DX600 on ACE2 from each particular species at the experimental conditions employed.

scholarly journals SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jinliang Wang ◽  
Guan Yang ◽  
Xinxin Wang ◽  
Zhiyuan Wen ◽  
Lei Shuai ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Spike Protein ◽  
Receptor Subtype ◽  
Converting Enzyme ◽  
Cell Binding ◽  
Angiotensin Converting Enzyme 2 ◽  
Metabotropic Glutamate ◽  
Coronavirus Infection

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) as a binding receptor to enter cells via clathrin-mediated endocytosis (CME). However, receptors involved in other steps of SARS-CoV-2 infection remain largely unknown. Here, we found that metabotropic glutamate receptor subtype 2 (mGluR2) is an internalization factor for SARS-CoV-2. Our results show that mGluR2 directly interacts with the SARS-CoV-2 spike protein and that knockdown of mGluR2 decreases internalization of SARS-CoV-2 but not cell binding. Further, mGluR2 is uncovered to cooperate with ACE2 to facilitate SARS-CoV-2 internalization through CME and mGluR2 knockout in mice abolished SARS-CoV-2 infection in the nasal turbinates and significantly reduced viral infection in the lungs. Notably, mGluR2 is also important for SARS-CoV spike protein- and Middle East respiratory syndrome coronavirus spike protein-mediated internalization. Thus, our study identifies a novel internalization factor used by SARS-CoV-2 and opens a new door for antiviral development against coronavirus infection.

scholarly journals Plasma from recovered COVID19 subjects inhibits spike protein binding to ACE2 in a microsphere-based inhibition assay

2020 ◽  
Author(s):  
Edward P. Gniffke ◽  
Whitney E. Harrington ◽  
Nicholas Dambrauskas ◽  
Yonghou Jiang ◽  
Olesya Trakhimets ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Antibody Response ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Inhibition Assay ◽  
Serological Tests ◽  
Angiotensin Converting Enzyme 2 ◽  
A Cell ◽  
Inhibitory Antibodies

AbstractHigh throughput serological tests that can establish the presence and functional activity of anti-SARS-COV2 antibodies are urgently needed. Here we present microsphere-based Flow Cytometry assays that quantify both anti-spike IgGs in plasma, and the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). First, we detected anti-spike-trimer IgGs in 22/24 and anti-spike-receptor-binding-domain (RBD) IgGs in 21/24 COVID+ subjects at a median of 36 (range 14-73) days following documented SARS-CoV-2 RNA (+) secretions. Next, we find that plasma from all 22/24 subjects with anti-trimer IgGs inhibited ACE2-trimer binding to a greater degree than controls, and that the degree of inhibition correlated with anti-trimer IgG levels. Depletion of trimer-reactive Igs from plasma reduced ACE2-trimer inhibitory capacity to a greater degree than depletion of RBD-reactive Igs, suggesting that inhibitory antibodies act by binding both within and outside of the RBD. Amongst the 24 subjects, presence of fever was associated with higher levels of anti-trimer IgG and inhibition of binding to human ACE2. This inhibition assay may be broadly useful to quantify the functional antibody response of recovered COVID19 patients or vaccine recipients in a cell-free assay system.

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