scholarly journals The SARS-CoV-2 infection in Thailand: analysis of spike variants complemented by protein structure insights

2022 ◽  
Author(s):  
Sirawit Ittisoponpisan ◽  
Shalip Yahangkiakan ◽  
Michael J.E. Sternberg ◽  
Alessia David
Keyword(s):  
Structural Change ◽  
Protein Structure ◽  
Genetic Variations ◽  
Spike Protein ◽  
Common Variants ◽  
Novel Variants ◽  
Prevalent Strain ◽  
Global Concern

Thailand was the first country outside China to officially report COVID-19 cases. Despite the strict regulations for international arrivals, up until February 2021, Thailand had been hit by two major outbreaks. With a large number of SARS-CoV-2 sequences collected from patients, the effects of many genetic variations, especially those unique to Thai strains, are yet to be elucidated. In this study, we analysed 439,197 sequences of the SARS-CoV-2 spike protein collected from NCBI and GISAID databases. 595 sequences were from Thailand and contained 52 variants, of which 6 had not been observed outside Thailand (p.T51N, p.P57T, p.I68R, p.S205T, p.K278T, p.G832C). These variants were not predicted to be of concern. We demonstrate that the p.D614G, although already present during the first Thai outbreak, became the prevalent strain during the second outbreak, similarly to what was described in other countries. Moreover, we show that the most common variants detected in Thailand (p.A829T, p.S459F and p.S939F) do not appear to cause any major structural change to the spike trimer or the spike-ACE2 interaction. Among the variants identified in Thailand was p.N501T. This variant, which involves an asparagine critical for spike-ACE2 binding, was not predicted to increase SARS-CoV-2 binding, thus in contrast to the variant of global concern p.N501Y. In conclusion, novel variants identified in Thailand are unlikely to increase the fitness of SARS-CoV-2. The insights obtained from this study could aid SARS-CoV-2 variants prioritisations and help molecular biologists and virologists working on strain surveillance.

scholarly journals Genetic and Epigenetic Variations of SARS-Cov-2 and Host Genes and Their Impact in Covid-19 Pandemic

2021 ◽  
Author(s):  
Muhammed Elayadeth Meethal ◽  
Punnoth Poonkuzhi Naseef ◽  
Mohamed Saheer Kuruniyan ◽  
Mansoor C Abdulla ◽  
Shyju Ollakkod ◽  
...  
Keyword(s):  
Rna Virus ◽  
Membrane Surface ◽  
Clinical Manifestations ◽  
Surface Protein ◽  
Genetic Variations ◽  
Third Wave ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Variants ◽  
The Impact ◽  
Second Wave

The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

Hb variants in Korea: effect on HbA1c using five routine methods

2017 ◽  
Vol 55 (8) ◽  
pp. 1234-1242 ◽  
Author(s):  
Yeo-Min Yun ◽  
Misuk Ji ◽  
Dae-Hyun Ko ◽  
Sail Chun ◽  
Gye Cheol Kwon ◽  
...  
Keyword(s):  
Glycated Hemoglobin ◽  
Local Population ◽  
Measurement Procedure ◽  
Common Variants ◽  
Blood Samples ◽  
Quantification Method ◽  
Target Values ◽  
Novel Variants ◽  
Standard Mode ◽  
The Impact

Abstract Background: Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Methods: Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Results: Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were “acceptable”, within the criteria of ±7% compared to IFCC RMP target values. However, percentage of “unacceptable” results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. Conclusions: HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

scholarly journals Cross-Neutralizing Activity of Monoclonal Antibodies Against N501Y Mutant Strain of SARS-CoV-2

2020 ◽  
Vol 9 (4) ◽  
pp. 41-45
Author(s):  
Ruxia Ding ◽  
Haixin Wang ◽  
Yi Yang ◽  
Liangshu Xie ◽  
Li Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Mutant Strain ◽  
Wild Type Strain ◽  
Neutralization Assay ◽  
Spike Protein ◽  
Wild Type ◽  
Neutralizing Activity ◽  
Theory Result ◽  
Global Concern ◽  
The Uk

The dominant N501Y mutation in the spike protein that SARS-CoV-2 virus uses to bind to the human ACE2 receptor were found in the UK, which has aroused global concern and worried. Mutations in spike protein may, in theory, result in more infectious and spreading more easily. In order to evaluate the broad-spectrum protective effect of the monoclonal antibodies(mAbs), we compared the neutralization activities of six prepared mAbs against SARS-CoV-2 with pseudovirus neutralization assay. Only one of them showed a decrease of 6 folds in neutralizing activity to N501Y mutant strain, compared with the wild type strain. We should continue to monitor emergence of new variants in different regions to study their infectivity and neutralization effect.

scholarly journals Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251585
Author(s):  
Pete Heinzelman ◽  
Philip A. Romero
Keyword(s):  
Clinical Trial ◽  
Genetic Variants ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Spike Protein ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Novel Variants ◽  
The Future ◽  
Fundamental Research

Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can facilitate the leveraging of ACE2 as an axis for treating and preventing COVID-19. In this work, we experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. These findings illuminate new links between ACE2 sequence and spike recognition, and could find substantial utility in further fundamental research that augments epidemiological analyses and clinical trial design in the contexts of both existing strains of SARS-CoV-2 and novel variants that may arise in the future.

scholarly journals Bioinformatics Analysis Unveils Certain Mutations Implicated in Spike Structure Damage and Ligand-Binding Site of Severe Acute Respiratory Syndrome Coronavirus 2

2021 ◽  
Vol 15 ◽  
pp. 117793222110182
Author(s):  
Emre Aktas
Keyword(s):  
Protein Structure ◽  
North America ◽  
Severe Acute Respiratory Syndrome ◽  
South Korea ◽  
Ligand Binding ◽  
Binding Sites ◽  
Spike Protein ◽  
Structure Damage ◽  
Ligand Binding Sites ◽  
New Mutations

There are certain mutations related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to these known mutations, other new mutations have been found across regions in this study. Based on the results, in which 4,326 SARS-CoV-2 whole sequences were used, some mutations are found to be peculiar with certain regions, while some other mutations are found in all regions. In Asia, mutations (3 different mutations in QLA46612 isolated from South Korea) were found in the same sequence. Although huge number of mutations are detected (more than 70 in Asia) by regions, according to bioinformatics tools, some of them which are G75V (isolated from North America), T95I (isolated from South Korea), G143V (isolated from North America), M177I (isolated from Asia), L293M (isolated from Asia), P295H (isolated from Asia), T393P (isolated from Europe), P507S (isolated from Asia), and D614G (isolated from all regions) (These color used only make correct) predicted a damage to spike’ protein structure. Furthermore, this study also aimed to reveal how binding sites of ligands change if the spike protein structure is damaged, and whether more than one mutation affects ligand binding. Mutations that were predicted to damage the structure did not affect the ligand-binding sites, whereas ligands’ binding sites were affected in those with multiple mutations. It is thought that this study will give a different perspective to both the vaccine SARS-CoV studies and the change in the structure of the spike protein belonging to this virus against mutations.

scholarly journals Identification of HLA-A*24:02-Restricted CTL Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 and Analysis of Their Conservation Using the Mutation Database of SARS-CoV-2 Variants

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Akira Takagi ◽  
Masanori Matsui
Keyword(s):  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Mutation Database ◽  
Novel Variants

COVID-19 vaccines have been designed to elicit neutralizing antibodies against the Spike protein of the original SARS-CoV-2, and hence they are less effective against variants. It is possible that novel variants will appear and escape from vaccine-elicited immunity.

scholarly journals Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens

2020 ◽  
Author(s):  
Yoya Vashi ◽  
Vipin Jagrit ◽  
Sachin Kumar
Keyword(s):  
T Cells ◽  
Protein Structure ◽  
Human Leukocyte Antigen ◽  
Surface Protein ◽  
Human Leukocyte ◽  
Spike Protein ◽  
T Cell Epitopes ◽  
Computational Approaches ◽  
Leukocyte Antigen ◽  
Epitope Binding

AbstractThe 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface. Out of which twenty are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics.

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