scholarly journals Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis

2020 ◽  
Author(s):  
Natalia G. Herrera ◽  
Nicholas C. Morano ◽  
Alev Celikgil ◽  
George I. Georgiev ◽  
Ryan J. Malonis ◽  
...  
Keyword(s):  
Cell Lines ◽  
Protein Microarray ◽  
The Novel ◽  
Antigenic Analysis ◽  
High Quality ◽  
Health Crisis ◽  
S Protein ◽  
Global Pandemic ◽  
S Proteins

ABSTRACTCoronavirus disease 2019 (COVID-19) is a global health crisis caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and there is a critical need to produce large quantities of high-quality SARS-CoV-2 Spike (S) protein for use in both clinical and basic science settings. To address this need, we have evaluated the expression and purification of two previously reported S protein constructs in Expi293F™ and ExpiCHO-S™ cells, two different cell lines selected for increased expression of secreted glycoproteins. We show that ExpiCHO-S™ cells produce enhanced yields of both SARS-CoV-2 S proteins. Biochemical, biophysical, and structural (cryo-EM) characterization of the SARS-CoV-2 S proteins produced in both cell lines demonstrate that the reported purification strategy yields high quality S protein (non-aggregated, uniform material with appropriate biochemical and biophysical properties). Importantly, we show that multiple preparations of these two recombinant S proteins from either cell line exhibit identical behavior in two different serology assays. We also evaluate the specificity of S protein-mediated host cell binding by examining interactions with proposed binding partners in the human secretome. In addition, the antigenicity of these proteins is demonstrated by standard ELISAs, and in a flexible protein microarray format. Collectively, we establish an array of metrics for ensuring the production of high-quality S protein to support clinical, biological, biochemical, structural and mechanistic studies to combat the global pandemic caused by SARS-CoV-2.

scholarly journals Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis

ACS Omega ◽  
2020 ◽  
Author(s):  
Natalia G. Herrera ◽  
Nicholas C. Morano ◽  
Alev Celikgil ◽  
George I. Georgiev ◽  
Ryan J. Malonis ◽  
...  
Keyword(s):  
Antigenic Analysis ◽  
S Protein

scholarly journals MicroRNAs and long non-coding RNAs as potential candidates to target specific motifs of SARS-CoV-2

2020 ◽  
Author(s):  
Lucia Natarelli ◽  
Luca Parca ◽  
Fabio Virgili ◽  
Tommaso Mazza ◽  
Christian Weber ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Specific Treatment ◽  
Leader Sequence ◽  
The Novel ◽  
Health Crisis ◽  
Global Pandemic ◽  
Pulmonary Arterial ◽  
Non Coding Rnas ◽  
Novel Coronavirus

Abstract The novel Coronavirus, SARS-CoV-2 disease (COVID-19) was defined as a global pandemic and induced a severe public health crisis in 2020. Covid-19 viral infection targets the human respiratory system and, at present, no specific treatment has been identified even though certain drugs have been studied and considered apparently effective in viral progression by reducing the complications in the lung epithelium. Researchers and clinicians are still struggling to find a vaccine or a specific innovative therapeutic strategy to counter COVID-19 infection.Here we describe our study indicating that SARS-CoV-2 genome contains motif sequences in the 5´UTR leader sequence that can be selectively recognized by specific human non-coding RNAs (ncRNAs), such as micro and long non-coding RNAs (miRNAs and lncRNA). Notably, some of these ncRNAs have been already utilized as oligo-based drugs in pulmonary and virus-associated diseases. We identified three selective motifs at the 5´UTR leader sequence of SARS-CoV-2 that allow viral recognition and binding of a specific group of miRNAs, some of them characterized by “GU” seed alignments. Additionally, one seed motif within miRNAs has been found to be able to bind the 5’UTR leader sequence. Among miRNAs having thermodynamically stable binding site against leader sequence and that are able interacted with Spike transcript some are involved in pulmonary arterial hypertension and anti-viral response, i.e. miR-204, miR-3661, and miR-1343. Moreover, several miRNA candidates have been already validated in vivo and specific oligo sequence are indeed available for their inhibition or overexpression.Four lncRNAs (H19, Hotair, Fendrr, and LINC05) directly interact with spike transcript (mRNA) and viral genome.In conclusion, we suggest that specific miRNAs and lncRNAs can be potential candidates to design oligonucleotide-drugs to treat COVID-19 and that our study can provide candidate hypothesis to be eventually tested in further experimental studies.

scholarly journals Geographies of the COVID-19 pandemic

2020 ◽  
Vol 10 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Reuben Rose-Redwood ◽  
Rob Kitchin ◽  
Elia Apostolopoulou ◽  
Lauren Rickards ◽  
Tyler Blackman ◽  
...  
Keyword(s):  
The Novel ◽  
Global Public Health ◽  
Special Issue ◽  
Current Crisis ◽  
Health Crisis ◽  
Global Pandemic ◽  
Theoretical Perspectives ◽  
Introductory Article ◽  
Novel Coronavirus ◽  
Political Economic

The spread of the novel coronavirus (SARS-CoV-2) has resulted in the most devastating global public health crisis in over a century. At present, over 10 million people from around the world have contracted the Coronavirus Disease 2019 (COVID-19), leading to more than 500,000 deaths globally. The global health crisis unleashed by the COVID-19 pandemic has been compounded by political, economic, and social crises that have exacerbated existing inequalities and disproportionately affected the most vulnerable segments of society. The global pandemic has had profoundly geographical consequences, and as the current crisis continues to unfold, there is a pressing need for geographers and other scholars to critically examine its fallout. This introductory article provides an overview of the current special issue on the geographies of the COVID-19 pandemic, which includes 42 commentaries written by contributors from across the globe. Collectively, the contributions in this special issue highlight the diverse theoretical perspectives, methodological approaches, and thematic foci that geographical scholarship can offer to better understand the uneven geographies of the Coronavirus/COVID-19.

scholarly journals Characteristics of Anti-SARS-CoV-2 Antibodies in Recovered COVID-19 Subjects

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 697
Author(s):  
Angela Huynh ◽  
Donald M. Arnold ◽  
James W. Smith ◽  
Jane C. Moore ◽  
Ali Zhang ◽  
...  
Keyword(s):  
Population Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
The Novel ◽  
Rt Pcr ◽  
S Protein ◽  
Viral Neutralization ◽  
Humoral Immune ◽  
Global Pandemic ◽  
Polymerase Chain ◽  
Ig G

Coronavirus Disease 2019 (COVID-19) is a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While detection of SARS-CoV-2 by polymerase chain reaction with reverse transcription (RT-PCR) is currently used to diagnose acute COVID-19 infection, serological assays are needed to study the humoral immune response to SARS-CoV-2. Anti-SARS-CoV-2 immunoglobulin (Ig)G/A/M antibodies against spike (S) protein and its receptor-binding domain (RBD) were characterized in recovered subjects who were RT-PCR-positive (n = 153) and RT-PCR-negative (n = 55) using an enzyme-linked immunosorbent assay (ELISA). These antibodies were also further assessed for their ability to neutralize live SARS-CoV-2 virus. Anti-SARS-CoV-2 antibodies were detected in 90.9% of resolved subjects up to 180 days post-symptom onset. Anti-S protein and anti-RBD IgG titers correlated (r = 0.5157 and r = 0.6010, respectively) with viral neutralization. Of the RT-PCR-positive subjects, 22 (14.3%) did not have anti-SARS-CoV-2 antibodies; and of those, 17 had RT-PCR cycle threshold (Ct) values > 27. These high Ct values raise the possibility that these indeterminate results are from individuals who were not infected or had mild infection that failed to elicit an antibody response. This study highlights the importance of serological surveys to determine population-level immunity based on infection numbers as determined by RT-PCR.

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 Characterization of SARS CoV-2 Antibodies in Breast Milk from 21 Women with Confirmed COVID-19 Infection

2021 ◽  
Author(s):  
Lars Bode ◽  
Kerri Bertrand ◽  
Julia A Najera ◽  
Annalee Furst ◽  
Gordon Honerkamp-Smith ◽  
...  
Keyword(s):  
Breast Milk ◽  
Protein Microarray ◽  
The Novel ◽  
Reading Frame ◽  
Milk Samples ◽  
Novel Coronavirus ◽  
The University ◽  
Infants And Young Children

One potential mechanism for protection from SARS-CoV-2 in infants and young children is through passive immunity via breast milk from a mother previously infected with the novel coronavirus. The primary objectives of this study were to establish the presence of SARS-CoV-2 specific IgA and IgG and to characterize the specific antigenic regions of SARS-CoV-2 proteins that were reactive with antibodies in breast milk from women with confirmed SARS-CoV-2 infection. Between March 2020 and September 2020, 21 women with confirmed SARS-CoV-2 infection were enrolled into Mommys Milk at the University of California, San Diego. Women donated serial breast milk samples. Breast milk samples were used to probe a multi-coronavirus protein microarray containing full-length proteins and variable length overlapping fragments of SARS-CoV-2 spike (S), envelope (E), membrane (M), nucleocapsid (N), and open reading frame (ORF) proteins. The breast milk samples contained IgA reactive with a variety of SARS-CoV-2 antigens. The most IgA-reactive SARS-CoV-2 proteins were N (42.9% of women responded to ≥1 N fragment) and S proteins (23.9% of women responded to ≥1 fragment of S1 or S2). Overall, individual COVID-19 cases had diverse and unique milk IgA profiles over the course of follow-up since onset of SARS-CoV-2 symptoms.

scholarly journals A review on the SARS-CoV-2 mediated global pandemic: proximal origin, pathogenicity and therapeutic approaches

2020 ◽  
Author(s):  
Soumi Chatterjee ◽  
Bikram Dhara ◽  
Dattatreya Mukherjee ◽  
Arup Kumar Mitra
Keyword(s):  
Vaccine Development ◽  
Geographical Area ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Global Pandemic ◽  
Viral Outbreak

The world is amidst a public health crisis as the pandemic has shook us to the core. The COVID-19 caused by the novel SARS-CoV-2 is of zoonotic origin and this tries to explain what could have been the possible proximal origins for the disease in humans. Our review aims at addressing the question like what structural or genomic vicissitude enabled the viral outbreak across genera and so efficiently infect the human populace across the globe. We also try to discuss the prospect of drug repurposing and scope for vaccine development considering the rapid genome modification of the virus. Another finding lies into the action of pre-existing drugs when they are applied in combination and probably that shades some light on the therapeutic approaches. Several investigation have been performed but we are still in search of a novel antiviral drug. With that vision, our focus shifted on the evaluation of existing drugs with positive response against the novel corona virus. We also try discussing certain trends including increased immunity to the disease in the population from a particular geographical area.

scholarly journals Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets

2020 ◽  
Author(s):  
Serena H. Chen ◽  
M. Todd Young ◽  
John Gounley ◽  
Christopher Stanley ◽  
Debsindhu Bhowmik
Keyword(s):  
Host Cells ◽  
Dynamics Simulation ◽  
Structural Flexibility ◽  
The Novel ◽  
Simulation Approach ◽  
S Protein ◽  
Therapeutic Development ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
S Proteins

AbstractThe emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.

scholarly journals PANDEMIC CRISIS AS A CATALYST OF DIGITALIZATION OF THE TOURISM INDUSTRY

2021 ◽  
pp. 22-29
Author(s):  
Oleg Havryliuk
Keyword(s):  
Structural Equation ◽  
Sharing Economy ◽  
Equation Model ◽  
Tourism Industry ◽  
New Paradigm ◽  
Economic Stability ◽  
High Quality ◽  
Health Crisis ◽  
Global Trends ◽  
Global Pandemic

The Covid-19 pandemic is not only the most serious global health crisis since the 1918 Great Influenza (Spanish flu), but is set to become one of the most economically costly pandemics in recent history. The experience with past epidemics provides some insights into various channels through which economic costs could arise, both in the short as well as longer term. At the same time, Covid-19 differs from previous episodes in several important ways. Notably, the globally synchronised lockdowns and trauma of financial markets reinforce one another into an unprecedented economic sudden stop. For these reasons, the Covid-19 global recession is unique. However, past epidemics can shed light on transmission channels to the economy, especially when stringent containment policies are not in place. The global pandemic has generated new problems and challenges related to further global and national socio-economic development, improvement of methods and tools of fundamentally high-quality business operation, interaction with customers in all areas of production and service. Modern global trends include efforts to overcome its consequences, as well as awareness of the new paradigm of consumer mentality. The aim of this study is to find out how far the digitization has already changed the tourism industry and what is still going to change in order to find potential benefits of digitization in the tourism industry. The results of the structural equation model approach show six main drivers (sales increase, classic booking, sharing economy, personalized offers, social media and customer reviews) that have a significant impact on the potential of digitization in the tourism industry. The dynamics of globalization and especially the COVID-19 coronavirus pandemic have generated stagnation and crisis in tourism, have raised new issues and challenges related to methods and tools of fundamentally high-quality business, customer interaction and service delivery, creation of "smart" technologies . Today’s global trends include the digitalization of all aspects of life, the rapid growth of e-commerce. Large firms and brands, as well as small and medium-sized enterprises, have launched new strategies of interaction with consumers, which are constantly being modified, especially depending on socio-economic stability and market fluctuations. The article examines the latest trends, strategies, problems and consequences of digitalization of the tourism business in the context of the crisis caused by the global pandemic, the phenomenon of "economy of impressions", targeted approach to needs and new opportunities for effective relationships with consumers. The newest directions of digitalization, modification of strategies and their prospects depending on social and economic stability and moods of consumers, in particular, in the context of the current epidemic of a coronavirus are analyzed. It is shown that the deterioration of the situation and the uncertainty of the further course of events naturally lead to the transformation / ratio of strategies towards online.

Jordan’s Public Health and Surveillance Health Policies: During and After COVID-19 (Preprint)

2020 ◽  
Author(s):  
Raeda AlQutob ◽  
Musa Taha Ajlouni ◽  
Mohamed Majed Abu Farraj ◽  
Immanuel Azaad Moonesar
Keyword(s):  
Public Health ◽  
Health System ◽  
Health Financing ◽  
World Health Organisation ◽  
World Health ◽  
The Novel ◽  
Future Health ◽  
Health Crisis ◽  
Global Pandemic ◽  
Novel Coronavirus

UNSTRUCTURED In contemporary times, the wave of the novel Coronavirus disease (COVID-19) classified by the World Health Organisation as global pandemic has unravelled systems and processes including health, economic and social. In the case of the Kingdom of Jordan, the COVID-19 crisis illustrated for the need and ability of the policy making institutions and ministries to take many effective policies, initiatives and procedures that were met with marked approval as the opinion polls conducted by government and private institutions showed. The success of these interventions during the crisis calls upon the country’s health system to take advantage of this experience in the next stage of recovery and resilience to develop, maintain its sustainability, as well as the improvement of a number of hubs to assist the Kingdom in facing the challenges resulting from any future health crisis such as epidemics or natural disasters. The viewpoint interventions that are the most paramount given the current situation as public health evidence must inform activities in seven priority health system areas to manage during and after the pandemic includes factors on: (1) governance and management; (2) service delivery and research; (3) human resources; (4) health information systems; (5) technology and medicine; (6) health financing; and (7) citizens, refugees and communities.

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