A vaccine built from potential immunogenic pieces derived from the SARS-CoV-2 spike glycoprotein: A computational approximation

<p>The latest outbreak of a new pathogenic coronavirus (SARS-CoV-2) is provoking a global health, economic and societal crisis. All-atom simulations enabled us to uncover the key molecular traits underlying the high affinity of SARS-CoV-2 spike glycoprotein towards its human receptor, providing a rationale to its high infectivity. Harnessing this knowledge can boost developing effective medical countermeasures to fight the current global pandemic.</p>

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Unique nCoV-2019 (COVID 19) spike glycoprotein processing by host protease: Analysis and Implication on infection

Current Proteomics ◽

10.2174/1570164617999200612115218 ◽

2020 ◽

Vol 17 ◽

Author(s):

Ajoy Basak ◽

Sarmistha Basak

Keyword(s):

World Health ◽

Spike Glycoprotein ◽

Binding Domains ◽

Corona Virus ◽

Global Pandemic ◽

High Infection ◽

Crucial Information ◽

Glycoprotein Processing ◽

Health Organization ◽

Host Reservoir

: The current global pandemic outbreak of a novel type of corona virus termed by World Health Organization as COVID-19 became an grave concern and worry to human health and world economy. Intense research efforts are now underway worldwide to combat and prevent the spread of this deadly disease. This zoonotic virus, a native to bat population is most likely transmitted to human via a host reservoir. Due to its close similarity to previously known SARS CoV (Severe Acute Respiratory Syndrome Corona Virus) of 2002 and related MERS CoV (Middle East Respiratory Syndrome Corona Virus) of 2012, it is also known as SARS CoV2. But unlike them it is far too infectious, virulent and lethal. Among its various proteins, the surface spike glycoprotein “S” has drawn significant attention because of its implication in viral recognition and host-virus fusion process. A detail comparative analysis of “S” proteins of SARS CoV (now called SARS CoV1), SARS CoV2 (COVID-19) and MERS CoV based on structure, sequence alignment, host cleavage sites, receptor binding domains, potential glycosylation and Cys-disulphide bridge locations has been performed. It revealed some key features and variations that may elucidate the high infection and virulence character of COVID-19. Moreover this crucial information may become useful in our quest for COVID-19 therapeutics and vaccines.

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Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200804161650 ◽

2020 ◽

Vol 20 ◽

Author(s):

Bipin Singh

Keyword(s):

Receptor Binding ◽

Point Mutations ◽

Binding Domain ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Angiotensin Converting Enzyme 2 ◽

Recent Outbreak ◽

Novel Coronavirus ◽

Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

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Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor

The Journal of Physical Chemistry B ◽

10.1021/acs.jpcb.1c02048 ◽

2021 ◽

Author(s):

Elhan Taka ◽

Sema Z. Yilmaz ◽

Mert Golcuk ◽

Ceren Kilinc ◽

Umut Aktas ◽

...

Keyword(s):

Spike Glycoprotein

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Tracking the interaction between single-wall carbon nanotube and SARS-Cov-2 spike glycoprotein: A molecular dynamics simulations study

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2021.104692 ◽

2021 ◽

pp. 104692

Author(s):

Masoumeh Jomhori Baloch ◽

Hamid Mosaddeghi ◽

Hamidreza Farzin

Keyword(s):

Molecular Dynamics ◽

Carbon Nanotube ◽

Molecular Dynamics Simulations ◽

Spike Glycoprotein ◽

Single Wall Carbon Nanotube ◽

Single Wall Carbon ◽

Dynamics Simulations

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Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein

ACS Pharmacology & Translational Science ◽

10.1021/acsptsci.1c00058 ◽

2021 ◽

Author(s):

Devivasha Bordoloi ◽

Ziyang Xu ◽

Michelle Ho ◽

Mansi Purwar ◽

Pratik Bhojnagarwala ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Spike Glycoprotein

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The Functional Consequences of the Novel Ribosomal Pausing Site in SARS-CoV-2 Spike Glycoprotein RNA

International Journal of Molecular Sciences ◽

10.3390/ijms22126490 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6490

Author(s):

Olga A. Postnikova ◽

Sheetal Uppal ◽

Weiliang Huang ◽

Maureen A. Kane ◽

Rafael Villasmil ◽

...

Keyword(s):

Amino Acid ◽

Insertion Sequence ◽

Experimental Studies ◽

Spike Protein ◽

Spike Glycoprotein ◽

Furin Cleavage ◽

New Host ◽

S Protein ◽

Furin Cleavage Site ◽

Ribosome Pausing

The SARS-CoV-2 Spike glycoprotein (S protein) acquired a unique new 4 amino acid -PRRA- insertion sequence at amino acid residues (aa) 681–684 that forms a new furin cleavage site in S protein as well as several new glycosylation sites. We studied various statistical properties of the -PRRA- insertion at the RNA level (CCUCGGCGGGCA). The nucleotide composition and codon usage of this sequence are different from the rest of the SARS-CoV-2 genome. One of such features is two tandem CGG codons, although the CGG codon is the rarest codon in the SARS-CoV-2 genome. This suggests that the insertion sequence could cause ribosome pausing as the result of these rare codons. Due to population variants, the Nextstrain divergence measure of the CCU codon is extremely large. We cannot exclude that this divergence might affect host immune responses/effectiveness of SARS-CoV-2 vaccines, possibilities awaiting further investigation. Our experimental studies show that the expression level of original RNA sequence “wildtype” spike protein is much lower than for codon-optimized spike protein in all studied cell lines. Interestingly, the original spike sequence produces a higher titer of pseudoviral particles and a higher level of infection. Further mutagenesis experiments suggest that this dual-effect insert, comprised of a combination of overlapping translation pausing and furin sites, has allowed SARS-CoV-2 to infect its new host (human) more readily. This underlines the importance of ribosome pausing to allow efficient regulation of protein expression and also of cotranslational subdomain folding.

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Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2

Computational and Mathematical Biophysics ◽

10.1515/cmb-2020-0119 ◽

2021 ◽

Vol 9 (1) ◽

pp. 81-89

Author(s):

Robert Penner

Keyword(s):

Free Energy ◽

Vaccine Development ◽

A Priori ◽

Structural Data ◽

Medical Sciences ◽

Spike Glycoprotein ◽

Mutagenic Potential ◽

Viral Mutation ◽

Novel Method ◽

Antiviral Targets

Abstract Tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method is reviewed and reformulated in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its mutations in multiple lineages. Key findings include: collections of mutagenic residues reoccur across strains, suggesting cooperative convergent evolution; most mutagenic residues do not participate in backbone hydrogen bonds; metastability of the glyco-protein limits the change of free energy through mutation thereby constraining selective pressure; and there are mRNA or virus-vector cargos targeting low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.

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