Covid-19 Mutations and How the Vaccine Enhances Immune Intelligence

Journal of Endocrinology and Metabolism Research ◽

10.37191/mapsci-2582-7960-2(1)-014 ◽

2021 ◽

Author(s):

Xanya Sofra

Keyword(s):

Amino Acid ◽

Viral Entry ◽

Open Reading Frames ◽

Spike Protein ◽

Single Amino Acid ◽

Immune Memory ◽

Type I ◽

Specific Amino Acid ◽

Adaptive Efficiency ◽

Acid Exchange

We traced the coronavirus classification and evolution, analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV. Despite their close kinship, SARS-CoV and Covid-19 display significant structural differences, including 380 amino acid substitutions, and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds. A single amino acid substitution such as replacing Aspartate (D) with Glycine (G) composes the D614G mutation that is around 20% more infectious than its predecessor 614D. The B117 variant, that exhibits a 70% transmissibility rate, harbours 23 mutants, each reflecting one amino acid exchange. We examined several globally spreading mutations, 501.V2, B1351, P1, and others, with respect to the specific amino acid conversions involved. Unlike previous versions of coronavirus, where random mutations eventually precipitate extinction, the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious, facilitating its ability to evade detection, thus challenging the effectiveness of a large variety of emerging vaccines. Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein, ultimately debilitating the virus from releasing its contents into the cell. Developing antibodies during the innate response, appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I, compromising adaptive efficiency to recognize the virus, possibly provoking a cytokine storm that injures vital organs. With respect to that perspective, the safety and effectiveness of different vaccines is evaluated and compared, including the Spike protein mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, or, finally, the live attenuated coronavirus that appears to demonstrate the greatest effectiveness, yet, encompass a relatively higher risk.

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Covid-19 Mutations and the Effect of Different Vaccines on Immune Memory

Journal of Endocrinology Research ◽

10.30564/jer.v3i1.2884 ◽

2021 ◽

Vol 3 (1) ◽

pp. 32

Author(s):

Xanya Sofra

Keyword(s):

Amino Acid ◽

Viral Entry ◽

Open Reading Frames ◽

Spike Protein ◽

Single Amino Acid ◽

Immune Memory ◽

Type I ◽

Specific Amino Acid ◽

Potential Safety ◽

Acid Exchange

We traced the coronavirus classification and evolution, analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV. Despite their close kinship, SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions, and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds. A single amino acid substitution such as replacing Aspartate (D) with Glycine (G) composes the D614G mutation that is around 20% more infectious than its predecessor 614D. The B117 variant, that exhibits a 70% transmissibility rate, harbours 23 mutants,each reflecting one amino acid exchange. We examined several globally spreading mutations, 501.V2, B1351, P1, and others, with respect to the specific amino acid conversions involved. Unlike previous versions of coronavirus, where random mutations eventually precipitate extinction, the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious, facilitating its ability to evade detection, thus challenging the effectiveness of a large variety of emerging vaccines. Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein, restricting the virus from releasing its contents into the cell. Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I, compromising adaptive efficiency to recognize the virus, possibly provoking a cytokine storm that injures vital organs. With respect to that perspective, the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, or, finally, the live attenuated coronavirus that appears to demonstrate the greatest effectiveness, yet,encompass a relatively higher risk.

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Charged Residues Flanking the Transmembrane Domain of Two Related Toxin–Antitoxin System Toxins Affect Host Response

Toxins ◽

10.3390/toxins13050329 ◽

2021 ◽

Vol 13 (5) ◽

pp. 329

Author(s):

Andrew Holmes ◽

Jessie Sadlon ◽

Keith Weaver

Keyword(s):

Amino Acid ◽

Enterococcus Faecalis ◽

Host Response ◽

Cytoplasmic Membrane ◽

Transmembrane Domain ◽

The Other ◽

Type I ◽

Transcriptomic Response ◽

Specific Amino Acid ◽

Transporter Protein

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

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Collapse of the native structure caused by a single amino acid exchange in human NAD (P)H:quinone oxidoreductase 1

FEBS Journal ◽

10.1111/febs.12975 ◽

2014 ◽

Vol 281 (20) ◽

pp. 4691-4704 ◽

Cited By ~ 35

Author(s):

Wolf‐Dieter Lienhart ◽

Venugopal Gudipati ◽

Michael K. Uhl ◽

Alexandra Binter ◽

Sergio A. Pulido ◽

...

Keyword(s):

Amino Acid ◽

Single Amino Acid ◽

Native Structure ◽

Amino Acid Exchange ◽

Acid Exchange

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An Extended α-Helix and Specific Amino Acid Residues Opposite the DNA-binding Surface of the cAMP Response Element Binding Protein Basic Domain Are Important for Human T Cell Lymphotropic Retrovirus Type I Tax Binding

Journal of Biological Chemistry ◽

10.1074/jbc.273.42.27339 ◽

1998 ◽

Vol 273 (42) ◽

pp. 27339-27346 ◽

Cited By ~ 15

Author(s):

Yong Tang ◽

Feng Tie ◽

Imre Boros ◽

Robert Harrod ◽

Mark Glover ◽

...

Keyword(s):

Amino Acid ◽

Camp Response Element Binding ◽

Type I ◽

Amino Acid Residues ◽

Camp Response Element ◽

Specific Amino Acid ◽

Human T Cell ◽

Binding Surface ◽

Element Binding Protein ◽

Α Helix

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A Mutation in the  Subunit of the Platelet Integrin IIbβ3 Identifies a Novel Region Important for Ligand Binding

Blood ◽

10.1182/blood.v93.3.918 ◽

1999 ◽

Vol 93 (3) ◽

pp. 918-924 ◽

Cited By ~ 19

Author(s):

Eileen Collins Tozer ◽

Elizabeth K. Baker ◽

Mark H. Ginsberg ◽

Joseph C. Loftus

Keyword(s):

Amino Acid ◽

Ligand Binding ◽

Single Amino Acid ◽

Chimeric Receptor ◽

Amino Acid Residues ◽

Genetic Approach ◽

Specific Amino Acid ◽

Transfected Cells ◽

Binding Function ◽

A Cell

Abstract An unbiased genetic approach was used to identify a specific amino acid residue in the IIb subunit important for the ligand binding function of the integrin IIbβ. Chemically mutagenized cells were selected by flow cytometry based on their inability to bind the ligand mimetic antibody PAC1 and a cell line containing a single amino acid substitution in IIb at position 224 (D→V) was identified. Although well expressed on the surface of transfected cells, IIbD224Vβ3 as well as IIbD224Aβ3 did not bind IIbβ3-specific ligands or a RGD peptide, a ligand shared in common with vβ3. Insertion of exon 5 of IIb, residues G193-W235, into the backbone of the v subunit did not enable the chimeric receptor to bind IIbβ3-specific ligands. However, the chimeric receptor was still capable of binding to a RGD affinity matrix. IIbD224 is not well conserved among other integrin  subunits and is located in a region of significant variability. In addition, amino acid D224 lies within a predicted loop of the recently proposed β-propeller model for integrin  subunits and is adjacent to a loop containing amino acid residues previously implicated in receptor function. These data support a role for this region in ligand binding function of the IIbβ3 receptor.

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Emergence of canine distemper in Bavarian wildlife associated with a specific amino acid exchange in the haemagglutinin protein

The Veterinary Journal ◽

10.1016/j.tvjl.2009.12.029 ◽

2011 ◽

Vol 187 (3) ◽

pp. 399-401 ◽

Cited By ~ 32

Author(s):

Karin Sekulin ◽

Angela Hafner-Marx ◽

Jolanta Kolodziejek ◽

Dirk Janik ◽

Peter Schmidt ◽

...

Keyword(s):

Amino Acid ◽

Canine Distemper ◽

Amino Acid Exchange ◽

Specific Amino Acid ◽

Acid Exchange

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Single Amino Acid Substitutions in the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Determine Viral Entry and Immunogenicity of a Major Neutralizing Domain

Journal of Virology ◽

10.1128/jvi.79.18.11638-11646.2005 ◽

2005 ◽

Vol 79 (18) ◽

pp. 11638-11646 ◽

Cited By ~ 38

Author(s):

Christopher E. Yi ◽

Lei Ba ◽

Linqi Zhang ◽

David D. Ho ◽

Zhiwei Chen

Keyword(s):

Amino Acid ◽

Severe Acute Respiratory Syndrome ◽

Viral Entry ◽

Neutralizing Antibodies ◽

Rational Design ◽

Antiviral Agents ◽

Single Amino Acid ◽

Major Mechanism ◽

The Difference

ABSTRACT Neutralizing antibodies (NAbs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) spike (S) glycoprotein confer protection to animals experimentally infected with the pathogenic virus. We and others previously demonstrated that a major mechanism for neutralizing SARS-CoV was through blocking the interaction between the S glycoprotein and the cellular receptor angiotensin-converting enzyme 2 (ACE2). In this study, we used in vivo electroporation DNA immunization and a pseudovirus-based assay to functionally evaluate immunogenicity and viral entry. We characterized the neutralization and viral entry determinants within the ACE2-binding domain of the S glycoprotein. The deletion of a positively charged region SΔ(422-463) abolished the capacity of the S glycoprotein to induce NAbs in mice vaccinated by in vivo DNA electroporation. Moreover, the SΔ(422-463) pseudovirus was unable to infect HEK293T-ACE2 cells. To determine the specific residues that contribute to related phenotypes, we replaced eight basic amino acids with alanine. We found that a single amino acid substitution (R441A) in the full-length S DNA vaccine failed to induce NAbs and abolished viral entry when pseudoviruses were generated. However, another substitution (R453A) abolished viral entry while retaining the capacity for inducing NAbs. The difference between R441A and R453A suggests that the determinants for immunogenicity and viral entry may not be identical. Our findings provide direct evidence that these basic residues are essential for immunogenicity of the major neutralizing domain and for viral entry. Our data have implications for the rational design of vaccine and antiviral agents as well as for understanding viral tropism.

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