RBD conjugate vaccine with built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern

2022 ◽  
Author(s):  
Shi-Hao Zhou ◽  
Ru-Yan Zhang ◽  
Haiwei Zhang ◽  
Yan-Ling Liu ◽  
Yu Wen ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
The World

The coronavirus 2019 (COVID-19) pandemic is causing serious impact in the world, safe and effective vaccines and medicines are the best method to combat the disease. The receptor-binding domain (RBD)...

scholarly journals Bacterial expression and purification of functional recombinant SARS-CoV-2 spike receptor binding domain

2021 ◽  
Author(s):  
Janani Prahlad ◽  
Lucas R. Struble ◽  
William E. Lutz ◽  
Savanna A. Wallin ◽  
Surender Khurana ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Disulfide Bonds ◽  
Rapid Diagnosis ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Expression And Purification ◽  
Protein Receptor ◽  
The World ◽  
Active Antigen

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 has applied significant pressure on overtaxed healthcare around the world, underscoring the urgent need for rapid diagnosis and treatment. We have developed a bacterial strategy for the expression and purification of the SARS-CoV-2 spike protein receptor binding domain using the CyDisCo system to create and maintain the correct disulfide bonds for protein integrity and functionality. We show that it is possible to quickly and inexpensively produce functional, active antigen in bacteria capable of recognizing and binding to the ACE2 (angiotensin-converting enzyme) receptor as well as antibodies in COVID-19 patient sera.

Binding Profile Assessment of N501Y: a More Infectious Mutation on the Receptor Binding Domain of SARS-CoV-2 Spike Protein

2021 ◽  
Author(s):  
Yuzhao Zhang ◽  
Xibing He ◽  
Viet Hoang Man ◽  
Jingchen Zhai ◽  
Beihong Ji ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rna Virus ◽  
Md Simulations ◽  
Binding Domain ◽  
Spike Protein ◽  
World Health ◽  
Receptor Binding Domain ◽  
Binding Profile ◽  
New Variant ◽  
The World

<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 and has accumulated nearly a hundred million reported infections thereafter. This highly transmissible and pathogenic coronavirus has caused a pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), which has caught extensive attention and greatly changed people’s lifestyles all over the world. As an RNA virus, SARS-CoV-2 mutates rapidly as the virus replicates. The world health organization is now closely monitoring the emergence of a new variant, N501Y, on the spike protein. This N501Y variant is found to have higher transmission ability and infectivity, and is believed to be related to the rapid increase of COVID-19 cases in December 2020 in the UK. It was recently reported that the N501Y variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies. The Tyr mutation at 501 is located at the receptor binding domain (RBD) of the spike protein, the area that directly contacts human ACE2 (hACE2). It’s urgent to figure out the driving force of the new mutant’s enhanced infectivity. Thus, a computational aided binding profile prediction is made to investigate the binding affinity alteration and potential structural change of the N501Y mutant. <a>The resulting structures of N501Y mutant from MD simulations could be used to develop drug inhibitors against hACE2/RBD binding. </a></p>

scholarly journals SARS-CoV-2 Variant of Concern Substitutions Alter Spike Glycoprotein Receptor Binding Domain Structure and Stability

2021 ◽  
Author(s):  
Daniel L Moss ◽  
Jay Rappaport
Keyword(s):  
Receptor Binding ◽  
Rapid Development ◽  
Structure And Function ◽  
Binding Domain ◽  
Amino Acid Substitutions ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Structure And Stability ◽  
The World ◽  
And Function

The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the subsequent COVID-19 pandemic has significantly impacted the world not just with disease and death but also economic turmoil. The rapid development and deployment of extremely effective vaccines against SARS-CoV-2 has made the end of the pandemic a reality within reach. However, as the virus spreads it has acquired mutations; and thus, variants of concern have emerged that are more infectious and reduce the efficacy of existing vaccines. While promising efforts are underway to combat these variants, the evolutionary pressures leading to these variants are poorly understood. To that end, here we have studied the effects of three amino-acid substitutions on the structure and function of the SARS-CoV-2 spike glycoprotein receptor-binding domain found in several variants of concern such as B.1.1.7, B.1.351 and P.1 that are now circulating. We found that these substitutions alter the RBD structure and stability, as well as its ability to bind to ACE2, which may have opposing and compensatory effects. These findings provide new insights into how these Variants of Concern (VOC) may have been selected to optimize infectivity while maintaining the structure and stability of the receptor binding domain.

scholarly journals Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19

2020 ◽  
Author(s):  
Kathleen M. McAndrews ◽  
Dara P. Dowlatshahi ◽  
Janine Hensel ◽  
Luis L. Ostrosky-Zeichner ◽  
Ramesh Papanna ◽  
...  
Keyword(s):  
Health Care ◽  
Antibody Response ◽  
Receptor Binding ◽  
Binding Domain ◽  
Spike Protein ◽  
Quantitative Detection ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Spike Glycoprotein ◽  
The World

AbstractDiagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale samples sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.

scholarly journals Emergence of Multiple SARS-CoV-2 Antibody Escape Variants in an Immunocompromised Host Undergoing Convalescent Plasma Treatment

mSphere ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Liang Chen ◽  
Michael C. Zody ◽  
Clara Di Germanio ◽  
Rachel Martinelli ◽  
Jose R. Mediavilla ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Plasma Treatment ◽  
Disease Severity ◽  
Receptor Binding ◽  
Vaccine Efficacy ◽  
Immunocompromised Host ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
The World

Over a year of the COVID-19 pandemic, distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages have arisen in multiple geographic areas around the world. SARS-CoV-2 variants of concern (VOCs), i.e., B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.2 (delta), harboring mutations and/or deletions in spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) regions showed evidence of increased transmissibility and disease severity and possible reduced vaccine efficacy.

scholarly journals Binding Profile Assessment of N501Y: a More Infectious Mutation on the Receptor Binding Domain of SARS-CoV-2 Spike Protein

2021 ◽  
Author(s):  
Yuzhao Zhang ◽  
Xibing He ◽  
Viet Hoang Man ◽  
Jingchen Zhai ◽  
Beihong Ji ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rna Virus ◽  
Md Simulations ◽  
Binding Domain ◽  
Spike Protein ◽  
World Health ◽  
Receptor Binding Domain ◽  
Binding Profile ◽  
New Variant ◽  
The World

<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 and has accumulated nearly a hundred million reported infections thereafter. This highly transmissible and pathogenic coronavirus has caused a pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), which has caught extensive attention and greatly changed people’s lifestyles all over the world. As an RNA virus, SARS-CoV-2 mutates rapidly as the virus replicates. The world health organization is now closely monitoring the emergence of a new variant, N501Y, on the spike protein. This N501Y variant is found to have higher transmission ability and infectivity, and is believed to be related to the rapid increase of COVID-19 cases in December 2020 in the UK. It was recently reported that the N501Y variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies. The Tyr mutation at 501 is located at the receptor binding domain (RBD) of the spike protein, the area that directly contacts human ACE2 (hACE2). It’s urgent to figure out the driving force of the new mutant’s enhanced infectivity. Thus, a computational aided binding profile prediction is made to investigate the binding affinity alteration and potential structural change of the N501Y mutant. <a>The resulting structures of N501Y mutant from MD simulations could be used to develop drug inhibitors against hACE2/RBD binding. </a></p>

scholarly journals Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 779
Author(s):  
Vladimir A. Gushchin ◽  
Inna V. Dolzhikova ◽  
Alexey M. Shchetinin ◽  
Alina S. Odintsova ◽  
Andrei E. Siniavin ◽  
...  
Keyword(s):  
Comparative Study ◽  
Receptor Binding ◽  
Mass Vaccination ◽  
Binding Domain ◽  
Virus Neutralization ◽  
Receptor Binding Domain ◽  
Neutralizing Activity ◽  
Genetic Lineages ◽  
The World ◽  
World Virus

Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from “Sputnik V”-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow.

scholarly journals Binding Profile Assessment of N501Y: a More Infectious Mutation on the Receptor Binding Domain of SARS-CoV-2 Spike Protein

2021 ◽  
Author(s):  
Yuzhao Zhang ◽  
Xibing He ◽  
Viet Hoang Man ◽  
Jingchen Zhai ◽  
Beihong Ji ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rna Virus ◽  
Md Simulations ◽  
Binding Domain ◽  
Spike Protein ◽  
World Health ◽  
Receptor Binding Domain ◽  
Binding Profile ◽  
New Variant ◽  
The World

<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 and has accumulated nearly a hundred million reported infections thereafter. This highly transmissible and pathogenic coronavirus has caused a pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), which has caught extensive attention and greatly changed people’s lifestyles all over the world. As an RNA virus, SARS-CoV-2 mutates rapidly as the virus replicates. The world health organization is now closely monitoring the emergence of a new variant, N501Y, on the spike protein. This N501Y variant is found to have higher transmission ability and infectivity, and is believed to be related to the rapid increase of COVID-19 cases in December 2020 in the UK. It was recently reported that the N501Y variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies. The Tyr mutation at 501 is located at the receptor binding domain (RBD) of the spike protein, the area that directly contacts human ACE2 (hACE2). It’s urgent to figure out the driving force of the new mutant’s enhanced infectivity. Thus, a computational aided binding profile prediction is made to investigate the binding affinity alteration and potential structural change of the N501Y mutant. <a>The resulting structures of N501Y mutant from MD simulations could be used to develop drug inhibitors against hACE2/RBD binding. </a></p>

Destabilizing the Structural Integrity of SARS-CoV2 Receptor Proteins by Curcumin Along with Hydroxychloroquine: An Insilco Approach for a Combination Therapy

2020 ◽  
Author(s):  
Akhileshwar Srivastava ◽  
Divya Singh
Keyword(s):  
Binding Energy ◽  
Combination Therapy ◽  
Receptor Binding ◽  
Structural Integrity ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Receptor Proteins ◽  
Main Protease ◽  
The Stability ◽  
Therapeutic Activities

Presently, an emerging disease (COVID-19) has been spreading across the world due to coronavirus (SARS-CoV2). For treatment of SARS-CoV2 infection, currently hydroxychloroquine has been suggested by researchers, but it has not been found enough effective against this virus. The present study based on in silico approaches was designed to enhance the therapeutic activities of hydroxychloroquine by using curcumin as an adjunct drug against SARS-CoV2 receptor proteins: main-protease and S1 receptor binding domain (RBD). The webserver (ANCHOR) showed the higher protein stability for both receptors with disordered score (<0.5). The molecular docking analysis revealed that the binding energy (-24.58 kcal/mol) of hydroxychloroquine was higher than curcumin (-20.47 kcal/mol) for receptor main-protease, whereas binding energy of curcumin (<a>-38.84</a> kcal/mol) had greater than hydroxychloroquine<a> (-35.87</a> kcal/mol) in case of S1 receptor binding domain. Therefore, this study suggested that the curcumin could be used as combination therapy along with hydroxychloroquine for disrupting the stability of SARS-CoV2 receptor proteins

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