A bioinformatic prediction of antigen presentation from SARS‐CoV‐2 spike protein revealed a theoretical correlation of HLA‐DRB1*01 with COVID‐19 fatality in Mexican population: An ecological approach

Romero-López, José Pablo; Carnalla, Martha; Pacheco-Olvera, Diana Laura; Ocampo-Godínez, Juan Moisés; Oliva-Ramírez, Jacqueline; Moreno-Manjón, Julia; Bernal-Alferes, Brian; López-Olmedo, Nancy; Garcı́a-Latorre, Ethel; Domínguez-López, María Lilia; Reyes-Sandoval, Arturo; Jiménez-Zamudio, L

doi:10.1002/jmv.26561

Cited by 34 publications

(36 citation statements)

References 40 publications

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“…Interestingly, HLA-A*02 alleles, among other class I and II alleles, were also identified as functional molecules for presenting SARS-CoV-2 peptides in a bioinformatic prediction study. In this same last report, an ecological study was also performed, and the HLA-DRB1*01 allele was found associated with COVID-19 fatality in a Mexican population; and, although the authors have addressed several limitations, the result must be taken with caution ( 47 ).…”

Section: Genetic Variants In the Study Of Covid-19 Susceptibility Andmentioning

confidence: 99%

Genetics Insight for COVID-19 Susceptibility and Severity: A Review

2021

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Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to a severe clinical course. The host genetic background influence on the susceptibility and outcome of multiples infectious diseases has been previously reported. Herein, we aimed to describe relevant identified genetic variants and those potentially related to the inter-individual variability of COVID-19 susceptibility and/or severity considering the physiopathological pathway of the disease The HLA-A*25:01, -B*15:27, -B*46:01, -C*01:02, and -C*07:29 alleles have been associated with COVID-19 susceptibility; while HLA-A*02:02, -B*15:03, and -C*12:03 have been identified as low-risk alleles. Variants in cytokine genes such as IL1B, IL1R1, IL1RN, IL6, IL17A, FCGR2A, and TNF could be related to disease susceptibility and cytokine storm, and/or COVID-19 complications (e.g., venous thrombosis). Several variants in ACE2 and TMPRSS2 affecting the expression of the receptors related to COVID-19 have been associated with the disease susceptibility and risk factors. Finally, two GWAS have identified the loci 3p21.31 (LZTFL1, SLC6A20, CCR9, FYCO1, CXCR6, and XCR1) and 9q34.2 (ABO) with COVID-19 severity. Heterogeneous results in the association of genetic variants with COVID-19 susceptibility and severity were observed. The mechanism of identified risk-genes and studies in different populations are still warranted.

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Section: Genetic Variants In the Study Of Covid-19 Susceptibility Andmentioning

confidence: 99%

Genetics Insight for COVID-19 Susceptibility and Severity: A Review

2021

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“…Like this study, many other investigations have successfully employed bioinformatic tools to predict the epitopic regions of different proteins in SARS-CoV-2/Wuhan. 30,31 However, experimental validations of these predictions are essentially required.…”

Section: Sequencementioning

confidence: 99%

Immunoinformatic analysis of structural and epitope variations in the spike and Orf8 proteins of SARS‐CoV‐2/B.1.1.7

Hussain

Shabbir

Amanullah

et al. 2021

Journal of Medical Virology

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A newly emerged strain of SARS-CoV-2 of B.1.1.7 lineage has caused a significant surge in the SARS-CoV-2 infections in the UK. In this study, changes in the epitopes of spike and orf8 proteins in SARS-CoV-2 of B.1.1.7 lineage were investigated. Genomic alignment of the SARS-CoV-2/B.1.1.7 with SARS-CoV-2/Wuhan showed the presence of several mutations in orf1a/b, spike, orf8, and N proteins of SARS-CoV-2/B.1.1.7. Molecular models of spike and orf8 proteins were constructed by homology modeling. Superimposition between the spike proteins of SARS-CoV-2/ Wuhan and SARS-CoV-2/B.1.1.7 showed noticeable variations in the spatial orientation in Val70-Asn74 and Thr250-Ser255 regions. This may have also resulted in the extension of the epitopic region at Ser244-Gly249 in the SARS-CoV-2/B.1.1.7 spike protein. Superimposition of the SARS-CoV-2/B.1.1.7 spike protein over Fabspike protein complexes of SARS-CoV-2/Wuhan also showed subtle variations in the antibody binding affinity targeting the N-terminal domain of the spike protein. Epitopic variations were also observed between the corresponding orf8 regions of SARS-CoV-2/Wuhan and SARS-CoV-2/B.1.1.7. Moreover, the presence of a stop codon at position 27 in orf8 connotes the emergence of two frames (orf8a and orf8b) in SARS-CoV-2, which further hampers its extracellular secretion, and in turn, immunogenicity. The findings of the present study could further be used to develop targeted immunotherapeutics.

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“…In Mexico, a significant negative correlation was found between the frequency of the class II HLA-DRB1*01 allele and the fatality rate in hospitalized patients, based on bioinformatic predictions. This allele can present at least nine epitopes of the M protein and 11 of the N protein, revealing its high relevance for SARS-CoV-2 immunity [151] .…”

Section: Associated Genetic Polymorphisms ( Table 3 )mentioning

confidence: 98%