Pattern of molecular mimicry between spike protein of SARS CoV2 and human thrombopoietin in beta, delta and omicron variants: a basic pathophysiological process of COVID-19 related thrombocytopenia.

Am J Blood Res 2022;12(2):60-63 www.AJBlood.us /ISSN:2160-1992/AJBR0141198 Original Article Pattern of molecular mimicry between spike protein of SARS CoV2 and human thrombopoietin in beta, delta and omicron variants: a basic pathophysiological process of COVID-19 related thrombocytopenia Rujittika Mungmunpuntipantip1, Viroj Wiwanitkit2 1 Private Academic Consultant, Bangkok, Thailand; 2Dr DY Patil University, Pune, India Received December 18, 2021; Accepted February 27, 2022; Epub April 15, 2022; Published April 30, 2022 Abstract: Thrombocytopenia is a possible problem in COVID-19. Hemorrhagic problem might be a result of thrombocytopenia in COVID-19. Due to the emergence of thrombocytopenia in COVID-19, the pathophysiology of thrombocytopenia in COVID-19 is currently a important topic in blood research. An important possible pathogenesis is the molecular mimicry. In variants of COVID-19, the change in spike might occur and the effect on molecular mimicry, which might further imply for association with thrombocytopenia. Specific study on this phenomenon can help better understand on the pathogenesis process of thrombocytopenia. In this study, the authors assessed the magnitude of molecular mimicry between the spike protein of SARS CoV2 and human thrombopoietin in wild type and important variants of COVID-19. In this work, the authors used a molecular similarity analysis to assess the impact of mutations in delta and delta plus variations. Each variant has a decreased similarity score and the omicron variant has the least similarity score. In this study, the decreased similarity score in the variant can imply decreased mimicry phenomenon. Hence, it can imply that there will be decreased COVID-19 thrombocytopenia problem in the variant. Keywords: COVID-19, mimicry, thrombocytopenia Introduction Coronavirus Disease 2019 (COVID-19), the current global public health issue, has already produced a pandemic since 2020. This coronaviral infection in the lungs can lead to major respiratory problems and, in the worst-case situation, death. COVID-19 has been associated to a number of strange clinical symptoms, including hematological issues [1]. COVID-19 is linked to thrombohemostatic disease [2-5], a potentially lethal illness. COVID-19 could develop a bleeding problem, resulting in a troubling clinical appearance. The problem of coagulation can affect a variety of organs [2-5]. Since the initial appearance of classical SARS CoV2 in late 2019, scientists have been keeping a tight eye on the pathogen’s genetic mutations all across the world [6]. Several pathogenic genetic mutations have been identified, and several variants have already proven to be trou- blesome novel variants [6, 7]. It’s feasible that a genetic alteration will have an impact, leading to the emergence of a new clinical ailment. The clinical problem caused by the pathogen’s genetic variation has already been recognized in COVID-19. In clinical virology, a mutation in the SARS-CoV-2 virus could emerge, and the new variant could be clinically significant. SARS CoV2 variations have been reported in a number of places. Focusing on hemostatic disorder, the thrombocytopenia is a possible problem in COVID-19 [9]. The hemorrhagic issue in COVID-19 could be due to thrombocytopenia [10]. In a report, the incidence of thrombocytopenia in the severe COVID-19 cases was about 12.4% [11]. In blood research, the pathogenesis of thrombocytopenia in COVID-19 is still not well clarified. An important possible pathogenesis is the molecular mimicry. In a recent report, it is proven that the molecular mimicry between the Mimicry between SARS COV2 and thrombopoietin Table 1. The similarity score between spike protein of SARS CoV2 and human thrombopoietin in wild type, beta, delta and omicron variants Type of SARS CoV2 Wild type Beta variant Delta variant Omicron variant Similarity score 55.7% 55.6% 54.3% 53.8% spike protein of pathogen and human thrombopoietin might induce thrombocytopenia in COVID-19 [12]. A change in spike in COVID-19 variations may occur, causing an influence on molecular mimicry, which could further suggest a link to thrombocytopenia. In this study, the authors assessed the magnitude of molecular mimicry between spike protein of SARS CoV2 and human thrombopoietin in wild type and important variants of COVID-19. The authors utilized a molecular similarity analysis to evaluate the impact of mutations in SARS CoV2 variants in this study. Materials and methods Medical molecular bioinformatics is used for conducting the present research. It’s one of a series of studies looking into the effects of molecular changes in SARS CoV2 mutants. The goal of this research is to assess the degree of similarity, which implies molecular mimicry, between the spike protein of SARS CoV2 and human thrombopoietin (GenBank: AAB33390.1). The study spike protein sequence of SARS CoV2 included both wild type as well as variants of SARS CoV2. The primary template for sequence of the spike protein sequence of wild type SARS CoV2 is derived from PubMED database, which has NCBI Reference Sequence: YP_009724390.1. For mutant types, in silico mutation assignment by PyMol (PyMol, version 2.4) is firstly done to derive sequences. The three studied variants in this study include a) beta (with K417N, E484K, and N501Y mutations), b) delta (T478K, P681R, and L452R assigned mutations), and c) omicron (with K417N, E484K, and N501Y mutations) (A67V, T95I, G142D, L212I, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, 61 N764K, D796Y, N856K, Q954H, N969K and L981F mutations). The conventional bioinformatics technique is used to compare the similarity of sequences. The molecular alignment between pair sequences is done. LALIGN/PLALIGN is the bioinformatics tool used in this work [13]. Basically, LALIGN/PLALIGN calculate non-intersecting local alignments of protein or DNA sequences to discover internal duplications [13]. LALIGN displays alignments and similarity [13]. The present study is not a mathematical modeling study but a sequence homology analysis. A pairwise sequence comparison is done based on comparative bioinformatic analysis using the previously mentioned bioinformatic tool. Regarding statistical analysis, the present bioinformatics comparison is based on Blocks Substitution Matrix (BLOSUM) [14]. In brief, the BLOSUM matrix is a substitution matrix used in bioinformatics for protein sequence alignment. To score alignments between evolutionarily diverse protein sequences, BLOSUM matrices are used. They are built on the basis of local alignments. The similarity score, which represents the percentage of homology between the investigated pairs sequences, is the result of BLOSUM matrices statistical analysis. The degree of homology is calculated using a simple mathematical computation based on percentages. The formula for calculation of homology score (...truncated)