scholarly journals SARS-CoV-2 Assays To Detect Functional Antibody Responses That Block ACE2 Recognition in Vaccinated Animals and Infected Patients

2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Susanne N. Walker ◽  
Neethu Chokkalingam ◽  
Emma L. Reuschel ◽  
Mansi Purwar ◽  
Ziyang Xu ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
The United States ◽  
Spike Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Single Experiment ◽  
Severe Respiratory Distress ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Significant Mortality

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.

scholarly journals High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity

2020 ◽  
Author(s):  
Jinghua Lu ◽  
Peter D. Sun
Keyword(s):  
Spike Protein ◽  
Affinity Binding ◽  
Ang Ii ◽  
High Affinity Binding ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity ◽  
Global Pandemic ◽  
Biological Substrates ◽  
Novel Coronavirus ◽  
Entry Receptor

AbstractA novel coronavirus (SARS-CoV-2) has emerged to a global pandemic and caused significant damages to public health. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides Ang II to control vasodilatation and permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we wonder how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ~3-10 fold when fluorogenic caspase-1 substrate and Bradykinin-analog peptides were used to characterize ACE2 activity. In addition, the enhancement was mediated by ACE2 binding of RBD domain of SARS-CoV-2 spike. These results highlighted the altered activity of ACE2 during SARS-CoV-2 infection and would shed new lights on the pathogenesis of COVID-19 and its complications for better treatments.

scholarly journals Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 57
Author(s):  
Zhi-Ling Zhu ◽  
Xiao-Dan Qiu ◽  
Shuo Wu ◽  
Yi-Tong Liu ◽  
Ting Zhao ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Blocking Effect ◽  
Spike Protein ◽  
Binding Affinities ◽  
The Novel ◽  
Converting Enzyme ◽  
Primary Method ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Effective Drugs

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

scholarly journals Immunologic aspect in diagnosis and treatment of SARS-COV-2 patients

2020 ◽  
Vol 3 (2) ◽  
pp. 113-121
Author(s):  
Sumaiya Yasin ◽  
Theophilus Bhatti ◽  
Muhammad Umer Farooqi ◽  
Farrukh Mateen
Keyword(s):  
Therapeutic Option ◽  
Lung Epithelial Cells ◽  
Confirmatory Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nasopharyngeal Swab ◽  
Angiotensin Converting Enzyme 2 ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Available Information ◽  
Respiratory Droplets

Recent worldwide outbreak of novel coronavirus disease (CoVID-19) has affected massive human population including Pakistan, and has caused a huge number of mortalities in few months. CoVID-19 is an infectious disease caused by a virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which is single stranded RNA enveloped beta coronavirus and affects lower respiratory tract. It transmits from human to human through respiratory droplets. It uses its S-protein to recognize ACE2 (Angiotensin Converting Enzyme-2) receptors in lung epithelial cells where it attaches and causes infection. The incubation period is 2-14 days. In pre-symptomatic phase, body’s immune system starts antibodies production. Significant antibodies are IgM and IgG that produces within 03-06 days and 8-12 days respectively. This review provides the available information about immunological aspects in terms of diagnosis and screening of CoVID-19 and potential therapeutic targets for combating SARS-CoV-2 infection. Immunologic techniques to detect these antibodies are ELISA (Enzyme-linked Immunosorbent Assay), CMIA (Chemiluminescent Micro particle Immunoassay) and ICT (Immunochromatographic Test). Among these, ELISA and CMIA are found to be highly specific and sensitive in convalescent phase of infection. While the fundamental confirmatory test for SARS-CoV-2 infection is RT-PCR (Reverse Transcription Polymerase Chain Reaction) which detects the viral RNA in respiratory samples preferably nasopharyngeal swab. Serological assays are essential to find out rate of infection, and most importantly antibody titers in recovered patients to be used for therapeutic purpose. After some successful studies Convalescent Plasma is considered as a good therapeutic option in the absence of specific antiviral therapy.

scholarly journals Covid-19 and food security: Jeopardy management and posterity deliberations

2021 ◽  
Vol 10 (2) ◽  
pp. 01-05
Author(s):  
Augustine Owusu-Addo ◽  
Atianashie Miracle A ◽  
Chukwuma Chinaza Adaobi ◽  
Larissa Agbemelo-Tsomafo
Keyword(s):  
Food Processing ◽  
Respiratory Illness ◽  
The United States ◽  
The Novel ◽  
Food Handling ◽  
Global Pandemic ◽  
Food Borne ◽  
Novel Coronavirus ◽  
Food Borne Infections ◽  
Safety Guidelines

COVID-19, also known as the ‘novel coronavirus disease 2019’, is a respiratory illness and the causative pathogen is officially named as ‘SARS-CoV-2’. Infections with SARS-CoV-2 have now been amplified to a global pandemic – as of April 3, 2020, nearly 1,018,000 cases have been confirmed in more than 195 countries, including more than 300,000 cases within the United States. Public safety guidelines are followed worldwide to stop the spread of COVID-19 and stay healthy. Despite COVID-19 is a respiratory illness with mode of invasion through the respiratory tract, not the gastrointestinal tract, an average food consumer is anxious and concerned about the food safety. Could an individual catch the deadly contagious COVID-19 from groceries brought home from the supermarket – or from the next restaurant takeout order? This brief review elucidates the epidemiology and pathobiological mechanism(s) of SARS-CoV-2 and its implications in food-borne infections, transmission via food surfaces, food processing and food handling.

scholarly journals Development of a Smartphone-Based Nanozyme-Linked Immunosorbent Assay for Quantitative Detection of SARS-CoV-2 Nucleocapsid Phosphoprotein in Blood

2021 ◽  
Vol 12 ◽  
Author(s):  
Bochao Liu ◽  
Ze Wu ◽  
Chaolan Liang ◽  
Jinhui Lu ◽  
Jinfeng Li ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Cross Reactivity ◽  
Quantitative Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Primary Screening ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Acid Test ◽  
Control Samples

Since December 2019, a novel coronavirus (SARS-CoV-2) has resulted in a global pandemic of coronavirus disease (COVID-19). Although viral nucleic acid test (NAT) has been applied predominantly to detect SARS-CoV-2 RNA for confirmation diagnosis of COVID-19, an urgent need for alternative, rapid, and sensitive immunoassays is required for primary screening of virus. In this study, we developed a smartphone-based nanozyme-linked immunosorbent assay (SP-NLISA) for detecting the specific nucleocapsid phosphoprotein (NP) of SARS-CoV-2 in 37 serum samples from 20 COVID-19 patients who were diagnosed by NAT previously. By using SP-NLISA, 28/37 (75.7%) serum samples were detected for NP antigens and no cross-reactivity with blood donors’ control samples collected from different areas of China. In a control assay using the conventional enzyme-linked immunosorbent assay (ELISA), only 7/37 (18.91%) serum samples were detected for NP antigens and no cross-reactivity with control samples. SP-NLISA could be used for rapid detection of SARS-CoV-2 NP antigen in primary screening of SARS-CoV-2 infected individuals.

Introduction

2021 ◽  
pp. 1-38
Author(s):  
Sara E. Gorman ◽  
Jack M. Gorman
Keyword(s):  
United States ◽  
Hemorrhagic Fever ◽  
The United States ◽  
Ebola Hemorrhagic Fever ◽  
Global Pandemic ◽  
The Face ◽  
Grave Problem ◽  
Novel Coronavirus ◽  
Vocal Minority

In 2014, a deadly epidemic of Ebola hemorrhagic fever ravaged three countries in West Africa. While the disease barely hit the United States, it caused widespread panic that sometimes threatened the safety of African immigrants in the United States. Five years later, a global pandemic of a novel coronavirus, later named COVID-19, quickly picked up speed around the world. In the face of a serious and very real threat, many Americans ignored the warnings and a vocal minority even insisted that the pandemic was not real. While the particulars of each of these examples might be quite different, they have something very important in common: science denial. This introductory chapter provides an overview of how such widespread science denialist views come into existence and how they spread. The authors outline the eight chapters of this book, which go into depth on different psychological mechanisms behind this phenomenon. Finally, they provide a preview of some of the solutions we have devised in response to this grave problem.

scholarly journals Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

2020 ◽  
Vol 94 (7) ◽  
Author(s):  
Yushun Wan ◽  
Jian Shang ◽  
Rachel Graham ◽  
Ralph S. Baric ◽  
Fang Li
Keyword(s):  
Animal Species ◽  
Atomic Level ◽  
Spike Protein ◽  
Structural Studies ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Receptor Usage ◽  
Receptor Recognition ◽  
Critical Residues ◽  
Novel Coronavirus

ABSTRACT Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV’s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV. IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

scholarly journals The spatiotemporal estimation of the risk and the international transmission of COVID-19: a global perspective

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuan-Chien Lin ◽  
Wan-Ju Chi ◽  
Yu-Ting Lin ◽  
Chun-Yeh Lai
Keyword(s):  
South Korea ◽  
Relevant Information ◽  
The United States ◽  
Global Perspective ◽  
Imported Case ◽  
Global Pandemic ◽  
Exponential Decrease ◽  
Risk Simulation ◽  
Novel Coronavirus ◽  
The Relationship

AbstractAn ongoing novel coronavirus outbreak (COVID-19) started in Wuhan, China, in December 2019. Currently, the spatiotemporal epidemic transmission, prediction, and risk are insufficient for COVID-19 but we urgently need relevant information globally. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of cases and estimate the future worldwide risk. Simulation results show that if there is no specific medicine for it, it will form a global pandemic. Taiwan, South Korea, Hong Kong, Japan, Thailand, and the United States are the most vulnerable. The relationship between each country's vulnerability and days before the first imported case occurred shows an exponential decrease. We successfully predicted the outbreak of South Korea, Japan, and Italy in the early stages of the global pandemic based on the information before February 12, 2020. The development of the epidemic is now earlier than we expected. However, the trend of spread is similar to our estimation.

scholarly journals SARS-CoV-2, ACE2 expression, and systemic organ invasion

2020 ◽  
Author(s):  
Usman M Ashraf ◽  
Ahmed A Abokor ◽  
Jonnelle M. Edwards ◽  
Emily W. Waigi ◽  
Rachel S. Royfman ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Normal Function ◽  
Multiple Organ ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Organs ◽  
Global Pandemic ◽  
Organ Systems ◽  
Novel Coronavirus ◽  
Severe Respiratory Illness ◽  
Organ Invasion

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in the humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

scholarly journals Cell-Mimicking Nanodecoys Protect Lung Cells by Neutralization of SARS-CoV-2 Spike Proteins

2020 ◽  
Author(s):  
Zhenhua Li ◽  
Phuong-Uyen C. Dinh ◽  
Kristen D. Popowski ◽  
Halle Lutz ◽  
Zhenzhen Wang ◽  
...  
Keyword(s):  
Viral Entry ◽  
Human Lung ◽  
Spike Protein ◽  
Inhalation Therapy ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Non Invasive ◽  
Global Pandemic ◽  
Integral Role

Abstract Coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has grown into a global pandemic, with no specific antiviral treatments or vaccines are yet approved. The viral receptor, angiotensin-converting enzyme 2 (ACE2), has been demonstrated to play an integral role in the pathogenesis of SARS-CoV-2, necessary for host cell viral entry. Inspired by this, we synthesized ACE2 nanodecoys from human lung spheroid cells (LSCs) capable of binding the Spike protein as a potential neutralization agent for SARS-CoV-2. Our results show LSC-nanodecoys has a high affinity and neutralization efficiency to both spike protein and chemically synthesized SARS-CoV-2 mimics. In addition, non-invasive inhalation therapy in mice showed successful delivery of the nanodecoy to the lungs, as well as in-vivo retention of the nanodecoys over 72 hours after a single administration. Furthermore, inhalation of nanodecoy accelerated the clearance of SARS-CoV-2 mimics from the lung and did not cause toxicity.

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