In silico investigation of binding affinities between human leukocyte antigen class I molecules and SARS-CoV-2 virus spike and ORF1ab proteins

Abstract

Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.

At the Root of 3 “Long” Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome

“…Indeed, HLA has been implicated in COVID course and severity. [145][146][147][148][149][150][151] In silico studies have documented Class I 147,148 and Class II HLA 151 alleles with high and low binding affinity to SARS-CoV-2 peptides, presumably resulting in, respectively, enhanced and reduced ability to present viral antigens to immune cells. To our knowledge no studies have documented HLAassociations with long-COVID; however, we have posited that reduced binding affinity due to HLA-antigen incongruence may contribute to persistent COVID antigens and subsequent downstream long-COVID sequelae.…”

Negative association between multiple sclerosis immunogenetic profile and in silico immunogenicities of 12 viruses

“…The INeo-Epp method 54 was used for T-cell receptor (TCR) epitope prediction using the INeo-Epp web tool via the INeo-Epp web form interface 55 . For that purpose, we split a given viral antigen (Table 6 ) to all possible 9-mer (nonamer) AA residue epitopes using a sliding window approach 56 – 58 (Fig. 10 ) and submitted each epitope to the web-application together with a specific HLA allele.…”

Melanoma and Human Leukocyte Antigen (HLA): Immunogenicity of 69 HLA Class I Alleles With 11 Antigens Expressed in Melanoma Tumors

“…The INeo-Epp method 20 was used for T-cell receptor (TCR) epitope prediction using the INeo-Epp web tool via the INeo-Epp web form interface. 24 For that purpose, we split a given melanoma antigen to all possible 9-mer AA residue epitopes using a sliding window approach [10][11][12] (Figure 1) and submitted each epitope to the web-application together with a specific HLA allele (Table 2). More specifically, we paired all epitopes with all alleles and obtained for each pair its percentile rank, a measure of binding affinity of the epitope-HLA allele complex; smaller percentile ranks indicate higher binding affinity.…”

“…However, the highly polymorphic nature of HLA contributes to variation in the binding groove; consequently, HLA alleles vary tremendously with respect to peptide binding capability, immunogenicity, and subsequent antigen elimination. [8][9][10][11][12][13][14][15][16] This variability also has implications for checkpoint blockade immunotherapy outcomes. Various immune-escape mechanisms exploited by tumors may disrupt the host immune response, permitting unchecked tumor cell proliferation.…”