scholarly journals Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Seth J. Zost ◽  
Pavlo Gilchuk ◽  
Rita E. Chen ◽  
James Brett Case ◽  
Joseph X. Reidy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Human Monoclonal Antibodies ◽  
S Protein ◽  
Global Pandemic ◽  
Antibody Discovery ◽  
Novel Coronavirus ◽  
Rapid Antibody

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.

scholarly journals Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2

2020 ◽  
Vol 25 (28) ◽  
Author(s):  
Zhiqiang Zheng ◽  
Vanessa Marthe Monteil ◽  
Sebastian Maurer-Stroh ◽  
Chow Wenn Yew ◽  
Carol Leong ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Common Cold ◽  
Sandwich Elisa ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
S Protein ◽  
Mammalian Cell Lines ◽  
Infected Cells ◽  
The Cross ◽  
Novel Coronavirus

Background A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2. Aim The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed. Methods The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein. Results An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format. Conclusion The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.

scholarly journals Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

2020 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Public Health ◽  
Receptor Binding ◽  
Cross Reactivity ◽  
Social Stability ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Palm Civet ◽  
Novel Coronavirus

AbstractThe current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs.SummarySerum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.

scholarly journals Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

2020 ◽  
Author(s):  
Xiangyu Chen ◽  
Ren Li ◽  
Zhiwei Pan ◽  
Chunfang Qian ◽  
Yang Yang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Angiotensin Converting Enzyme ◽  
Virus Disease ◽  
Pseudotyped Virus ◽  
Converting Enzyme ◽  
Human Monoclonal Antibodies ◽  
Human Mabs ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

FEATURES OF THE COURSE AND TACTICS OF MANAGING CHILDREN WITH KIDNEYS AND URINARY TRACT DISEASES DURING THE PANDEMIC OF NEW CORONAVIRUS INFECTION COVID-19

2021 ◽  
Vol 100 (4) ◽  
pp. 74-79
Author(s):  
I.M. Kagantsov ◽  
◽  
V.V. Sizonov ◽  
V.G. Svarich ◽  
K.P. Piskunov ◽  
...  
Keyword(s):  
Age Groups ◽  
Clinical Manifestations ◽  
Routine Care ◽  
The Novel ◽  
Urinary System ◽  
Death Rates ◽  
Global Pandemic ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Significant Health

The novel coronavirus infection (SARS-CoV-2), which first appeared in Wuhan, China in December 2019, has been declared a global pandemic by WHO. COVID-19 affects people of all age groups. The disease in children is usually asymptomatic or mild compared to adults, and with a significantly lower death rates. Data on kidney damage in children with COVID-19, as well as the effect of coronavirus infection on the course of diseases of the genitourinary system, are limited, the risks of contracting a new coronavirus infection in children with significant health problems, including those with chronic kidney disease, remain uncertain. The pandemic has affected the activities of surgeons treating diseases of the urinary system in children. Since the prospects for the end of the pandemic are vague, it is necessary to formulate criteria for selecting patients who can and should be provided with routine care in the pandemic. The purpose of this review is to highlight the features of the clinical manifestations and treatment of children with COVID-19, occurring against the background of previous renal pathology or complicating its course.

scholarly journals Emergence of SARS-CoV-2 through recombination and strong purifying selection

2020 ◽  
Vol 6 (27) ◽  
pp. eabb9153 ◽  
Author(s):  
Xiaojun Li ◽  
Elena E. Giorgi ◽  
Manukumar Honnayakanahalli Marichannegowda ◽  
Brian Foley ◽  
Chuan Xiao ◽  
...  
Keyword(s):  
Host Species ◽  
Purifying Selection ◽  
New Drugs ◽  
Evolutionary Constraints ◽  
Binding Motif ◽  
The Novel ◽  
Global Pandemic ◽  
Show Evidence ◽  
Human Coronaviruses ◽  
Novel Coronavirus

COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species, together with frequent recombination among coronaviruses, suggests a common evolutionary mechanism that could lead to new emerging human coronaviruses.

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 Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

scholarly journals The Impact of Armed Conflict on the Epidemiological Situation of COVID-19 in Libya, Syria and Yemen

2021 ◽  
Vol 9 ◽  
Author(s):  
Mohamed A. Daw
Keyword(s):  
Armed Conflict ◽  
Early Stage ◽  
Armed Conflicts ◽  
Cumulative Number ◽  
The Novel ◽  
Global Pandemic ◽  
Large Numbers ◽  
Public Data ◽  
Novel Coronavirus ◽  
The Impact

Background: Since the Arab uprising in 2011, Libya, Syria and Yemen have gone through major internal armed conflicts. This resulted in large numbers of deaths, injuries, and population displacements, with collapse of the healthcare systems. Furthermore, the situation was complicated by the emergence of COVID-19 as a global pandemic, which made the populations of these countries struggle under unusual conditions to deal with both the pandemic and the ongoing wars. This study aimed to determine the impact of the armed conflicts on the epidemiology of the novel coronavirus (SARS-CoV-2) within these war-torn countries and highlight the strategies needed to combat the spread of the pandemic and its consequences.Methods: Official and public data concerning the dynamics of the armed conflicts and the spread of SARS-COV-2 in Libya, Syria and Yemen were collected from all available sources, starting from the emergence of COVID-19 in each country until the end of December 2020. Datasets were analyzed by a set of statistical techniques and the weekly resolved data were used to probe the link between the intensity levels of the conflict and the prevalence of COVID-19.Results: The data indicated that there was an increase in the intensity of the violence at an early stage from March to August 2020, when it approximately doubled in the three countries, particularly in Libya. During that period, few cases of COVID-19 were reported, ranging from 5 to 53 cases/day. From September to December 2020, a significant decline in the intensity of the armed conflicts was accompanied by steep upsurges in the rate of COVID-19 cases, which reached up to 500 cases/day. The accumulative cases vary from one country to another during the armed conflict. The highest cumulative number of cases were reported in Libya, Syria and Yemen.Conclusions: Our analysis demonstrates that the armed conflict provided an opportunity for SARS-CoV-2 to spread. The early weeks of the pandemic coincided with the most intense period of the armed conflicts, and few cases were officially reported. This indicates undercounting and hidden spread during the early stage of the pandemic. The pandemic then spread dramatically as the armed conflict declined, reaching its greatest spread by December 2020. Full-blown transmission of the COVID-19 pandemic in these countries is expected. Therefore, urgent national and international strategies should be implemented to combat the pandemic and its consequences.

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.

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