A structural homology approach to identify potential cross-reactive antibody responses following SARS-CoV-2 infection

Abstract

The emergence of the novel SARS-CoV-2 virus is the most important public-health issue of our time. Understanding the diverse clinical presentations of the ensuing disease, COVID-19, remains a critical unmet need. Here we present a comprehensive listing of the diverse clinical indications associated with COVID-19. We explore the theory that anti-SARS-CoV-2 antibodies could cross-react with endogenous human proteins driving some of the pathologies associated with COVID-19. We describe a novel computational approach to estimate structural homology between SARS-CoV-2 proteins and human proteins. Antibodies are more likely to interrogate 3D-structural epitopes than continuous linear epitopes. This computational workflow identified 346 human proteins containing a domain with high structural homology to a SARS-CoV-2 Wuhan strain protein. Of these, 102 proteins exhibit functions that could contribute to COVID-19 clinical pathologies. We present a testable hypothesis to delineate unexplained clinical observations vis-à-vis COVID-19 and a tool to evaluate the safety-risk profile of potential COVID-19 therapies.

Life‐threatening severe acute respiratory syndrome coronavirus‐2 mRNA vaccine‐associated myocarditis after COVID‐19 myocarditis

“…4 It is reported that some anti-SARS-CoV-2 spike antibodies react with the myosin-containing human protein structure. 5 This hypothesis may also be persuasive in our case because the pathogenic T cells activated in the SARS-CoV-2 mRNA infection could behave as inducers of SARS-CoV-2 mRNA vaccine-associated myocarditis.…”

“…Molecular mimicry between the spike protein antigen and autologous cardiac antigen has been postulated as one of the mechanisms of SARS‐CoV‐2 mRNA vaccine‐associated myocarditis 4 . It is reported that some anti‐SARS‐CoV‐2 spike antibodies react with the myosin‐containing human protein structure 5 . This hypothesis may also be persuasive in our case because the pathogenic T cells activated in the SARS‐CoV‐2 mRNA infection could behave as inducers of SARS‐CoV‐2 mRNA vaccine‐associated myocarditis.…”

The histological and immunopathological landscape of lung autopsy sample of COVID 19

“…In the study by JR McGill et al (2022) (25), which was conducted with the aim of identifying antibody responses and potential antibody reactions in COVID-19 patients, It appears that anti-SARS-CoV-2 antibodies can cross-react with endogenous human proteins that drive some of the pathologies associated with COVID-19. In line with the results of our study, the results of this study showed that the anti-catenin antibody has high reactivity in COVID-19 patients and can play a significant role in the process of pathogenesis.…”

Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

“…При картировании антигенных эпитопов выявлена гомология между компонентами SARS-CoV-2 (S-белок, нуклеопротеин) и тканевыми антигенами, включая митохондрии M2, F-актин, тропонин и др. При изучении структурной гомологии между белками SARS-CoV-2 и белками человека с использованием расчетного (computational) метода идентифицировано 346 белков, содержащих домены с высокой структурной гомологией с белком SARS-CoV-2, среди которых 102 белка обладали функциональной активностью, потенциально участвующей в патогенезе COVID-19 [120].…”