Biology subjects

Nunez-Castilla, J.

Publications and source records attributed to Nunez-Castilla, J..

3 recordsLinked to original sources

bioRxiv2022

EMoMiS: A Pipeline for Epitope-based Molecular Mimicry Search in Protein Structures with Applications to SARS-CoV-2

MotivationEpitope-based molecular mimicry occurs when an antibody cross-reacts with two different antigens due to structural and chemical similarities. Molecular mimicry between proteins from two viruses can lead to beneficial cross-protection when the antibodies produced by exposure to one also react with the other. On the other hand, mimicry between a protein from a pathogen and a human protein can lead to auto-immune disorders if the antibodies resulting from exposure to the virus end up interacting with host proteins. While cross-protection can suggest the possible reuse of vaccines developed for other pathogens, cross-reaction with host proteins may explain side effects. There are no computational tools available to date for a large-scale search of antibody cross-reactivity. ResultsWe present a comprehensive Epitope-based Molecular Mimicry Search (EMoMiS) pipeline for computational molecular mimicry searches. EMoMiS, when applied to the SARS-CoV-2 Spike protein, identified eight examples of molecular mimicry with viral and human proteins. These findings provide possible explanations for (a) differential severity of COVID-19 caused by cross-protection due to prior vaccinations and/or exposure to other viruses, and (b) commonly seen COVID-19 side effects such as thrombocytopenia and thrombophilia. Our findings are supported by previously reported research but need validation with laboratory experiments. The developed pipeline is generic and can be applied to find mimicry for novel pathogens. It has applications in improving vaccine design. AvailabilityThe developed Epitope-based Molecular Mimicry Search Pipeline (EMoMiS) is available from https://biorg.cs.fiu.edu/emomis/. Contactgiri@cs.fiu.edu

bioinformatics↗

bioRxiv2021

Epitopedia: identifying molecular mimicry of known immune epitopes

Upon infection, foreign antigenic proteins stimulate the hosts immune system to produce antibodies targeting the pathogen. These antibodies bind to regions on the antibody called epitopes. Structural similarity (molecular mimicry) of epitopes between an infecting pathogen and host proteins or other pathogenic proteins the host has previously encountered can impact the host immune response to the pathogen and may lead to cross-reactive antibodies. The ability to identify potential regions of molecular mimicry in a pathogen can illuminate immune effects which are especially important to pathogen treatment and vaccine design. Here we present Epitopedia, a software pipeline that facilitates the identification of regions that may exhibit potential three-dimensional molecular mimicry between an antigenic pathogen protein and known immune epitopes as catalogued by the immune epitope database (IEDB). Epitopedia is open-source software released under the MIT license and is freely available on GitHub, including a Docker container with all other software dependencies preinstalled. We performed an analysis describing how various secondary structure states, identity between pentapeptide pairs, and identity between the parent sequences of pentapeptide pairs affects RMSD. We found that pentapeptides pairs in a helical conformation had considerably lower RMSD values than those in Extended or Coil conformations. We also found that RMSD is significantly increased when pentapeptide pairs are from non-homologous sequences.

bioinformatics↗

bioRxiv2021

Molecular mimicry between Spike and human thrombopoietin may induce thrombocytopenia in COVID-19

SARS-CoV-2 causes COVID-19, a disease curiously resulting in varied symptoms and outcomes, ranging from asymptomatic to fatal. Autoimmunity due to cross-reacting antibodies resulting from molecular mimicry between viral antigens and host proteins may provide an explanation. We computationally investigated molecular mimicry between SARS-CoV-2 Spike and known epitopes. We discovered molecular mimicry hotspots in Spike and highlight two examples with tentative autoimmune potential and implications for understanding COVID-19 complications. We show that a TQLPP motif in Spike and thrombopoietin shares similar antibody binding properties. Antibodies cross-reacting with thrombopoietin may induce thrombocytopenia, a condition observed in COVID-19 patients. Another motif, ELDKY, is shared in multiple human proteins such as PRKG1 and tropomyosin. Antibodies cross-reacting with PRKG1 and tropomyosin may cause known COVID-19 complications such as blood-clotting disorders and cardiac disease, respectively. Our findings illuminate COVID-19 pathogenesis and highlight the importance of considering autoimmune potential when developing therapeutic interventions to reduce adverse reactions.

bioinformatics↗