Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach

Pablo Isaac Estrada; Alberto Velez-van-Meerbeke; Andres Felipe Cuspoca Orduz

doi:10.1016/j.csbj.2022.10.022

Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach

Título traducido de la contribución: Mimetismo molecular de la proteína espiga del SARS-CoV-2 en el sistema nervioso: un enfoque bioinformático

Pablo Isaac Estrada, Alberto Velez-van-Meerbeke, Andres Felipe Cuspoca Orduz

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

11 Citas (Scopus)

Resumen

Introducción
El desarrollo de vacunas contra el coronavirus 2 (SARS-CoV-2) de la neumonía asiática en un tiempo récord para hacer frente a la actual pandemia de enfermedad por coronavirus 2019 (COVID-19) ha generado incertidumbre sobre su uso y la aparición de reacciones neurológicas adversas. La proteína de pico (SP) del SARS-CoV-2 se utiliza para producir anticuerpos neutralizantes y estimular la inmunidad innata. Sin embargo, considerando las alteraciones en el sistema nervioso (SN) provocadas por la COVID-19, las reacciones cruzadas son plausibles.

Objetivo
Identificar péptidos en proteínas similares a SP de Homo sapiens involucradas en la homeostasis de mielina y axones que pueden verse afectadas debido al mimetismo molecular por anticuerpos y células T inducidas por la interacción con SP.

Materiales y métodos
Se utilizó un enfoque bioinformático. Para seleccionar las proteínas de H. sapiens a estudiar, se extrajeron procesos biológicos relacionados categorizados según la ontología genética mediante la construcción de una red de interacción proteína-proteína. Como proteína de consulta se utilizó la proteína de mielina periférica 22 , un componente importante de la mielina en el sistema nervioso periférico. Los dominios extracelulares y las regiones susceptibles de reconocimiento por anticuerpos se extrajeron de UniProt. En el estudio de las células T, se evaluó la similitud de secuencia lineal entre las proteínas de H. sapiens y SP mediante BLASTp. Este estudio consideró la similitud en términos de grupos bioquímicos por residuo y afinidad con el complejo principal de histocompatibilidad humano (antígeno leucocitario humano I), que se evaluaron utilizando Needle y NetMHCpan 4.1, respectivamente.

Resultados
Se identificó una gran cantidad de pentapéptidos compartidos entre las proteínas SP y H. sapiens . Sin embargo, sólo un pequeño grupo de 39 proteínas estaba vinculado a la homeostasis de los axones y la mielina. En particular, algunas proteínas, como el fosfacano, la atractina y la teneurina-4, eran objetivos susceptibles de las células B y T. Se encontró que otras proteínas estrechamente relacionadas con los componentes de mielina en el NS, como la glicoproteína asociada a mielina, comparten al menos un pentámero con SP en dominios extracelulares.

Conclusión
En H. sapiens se identificaron proteínas implicadas en el mantenimiento de la conducción nerviosa en el sistema nervioso central y periférico. Según estos hallazgos, se recomienda reevaluar la composición de la vacuna para prevenir posibles efectos secundarios neurológicos.

Título traducido de la contribución	Mimetismo molecular de la proteína espiga del SARS-CoV-2 en el sistema nervioso: un enfoque bioinformático
Idioma original	Inglés estadounidense
Páginas (desde-hasta)	6041-6054
Número de páginas	14
Publicación	Computational and Structural Biotechnology Journal
Volumen	20
DOI	https://doi.org/10.1016/j.csbj.2022.10.022
Estado	Publicada - oct. 27 2022

Áreas temáticas de ASJC Scopus

Biotecnología
Biofísica
Biología estructural
Bioquímica
Genética
Informática aplicada

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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title = "Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach",

abstract = "Introduction: The development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in record time to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty about their use and the appearance of adverse neurological reactions. The SARS-CoV-2 spike protein (SP) is used to produce neutralizing antibodies and stimulate innate immunity. However, considering the alterations in the nervous system (NS) caused by COVID- 19, cross-reactions are plausible. Objective: To identify peptides in Homo sapiens SP-like proteins involved in myelin and axon homeostasis that may be affected due to molecular mimicry by antibodies and T cells induced by interaction with SP. Materials and methods: A bioinformatics approach was used. To select the H. sapiens proteins to be studied, related biological processes categorized based on gene ontology were extracted through the construction of a protein–protein interaction network. Peripheral myelin protein 22, a major component of myelin in the peripheral nervous system, was used as the query protein. The extracellular domains and regions susceptible to recognition by antibodies were extracted from UniProt. In the study of T cells, linear sequence similarity between H. sapiens proteins and SP was assessed using BLASTp. This study considered the similarity in terms of biochemical groups per residue and affinity to the human major histocompatibility complex (human leukocyte antigen I), which were evaluated using Needle and NetMHCpan 4.1, respectively. Results: A large number of shared pentapeptides between SP and H. sapiens proteins were identified. However, only a small group of 39 proteins was linked to axon and myelin homeostasis. In particular, some proteins, such as phosphacan, attractin, and teneurin-4, were susceptible targets of B and T cells. Other proteins closely related to myelin components in the NS, such as myelin-associated glycoprotein, were found to share at least one pentamer with SP in extracellular domains. Conclusion: Proteins involved in the maintenance of nerve conduction in the central and peripheral NS were identified in H. sapiens. Based on these findings, re-evaluation of the vaccine composition is recommended to prevent possible neurological side effects.",

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AU - Cuspoca Orduz, Andres Felipe

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N2 - Introduction: The development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in record time to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty about their use and the appearance of adverse neurological reactions. The SARS-CoV-2 spike protein (SP) is used to produce neutralizing antibodies and stimulate innate immunity. However, considering the alterations in the nervous system (NS) caused by COVID- 19, cross-reactions are plausible. Objective: To identify peptides in Homo sapiens SP-like proteins involved in myelin and axon homeostasis that may be affected due to molecular mimicry by antibodies and T cells induced by interaction with SP. Materials and methods: A bioinformatics approach was used. To select the H. sapiens proteins to be studied, related biological processes categorized based on gene ontology were extracted through the construction of a protein–protein interaction network. Peripheral myelin protein 22, a major component of myelin in the peripheral nervous system, was used as the query protein. The extracellular domains and regions susceptible to recognition by antibodies were extracted from UniProt. In the study of T cells, linear sequence similarity between H. sapiens proteins and SP was assessed using BLASTp. This study considered the similarity in terms of biochemical groups per residue and affinity to the human major histocompatibility complex (human leukocyte antigen I), which were evaluated using Needle and NetMHCpan 4.1, respectively. Results: A large number of shared pentapeptides between SP and H. sapiens proteins were identified. However, only a small group of 39 proteins was linked to axon and myelin homeostasis. In particular, some proteins, such as phosphacan, attractin, and teneurin-4, were susceptible targets of B and T cells. Other proteins closely related to myelin components in the NS, such as myelin-associated glycoprotein, were found to share at least one pentamer with SP in extracellular domains. Conclusion: Proteins involved in the maintenance of nerve conduction in the central and peripheral NS were identified in H. sapiens. Based on these findings, re-evaluation of the vaccine composition is recommended to prevent possible neurological side effects.

AB - Introduction: The development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in record time to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty about their use and the appearance of adverse neurological reactions. The SARS-CoV-2 spike protein (SP) is used to produce neutralizing antibodies and stimulate innate immunity. However, considering the alterations in the nervous system (NS) caused by COVID- 19, cross-reactions are plausible. Objective: To identify peptides in Homo sapiens SP-like proteins involved in myelin and axon homeostasis that may be affected due to molecular mimicry by antibodies and T cells induced by interaction with SP. Materials and methods: A bioinformatics approach was used. To select the H. sapiens proteins to be studied, related biological processes categorized based on gene ontology were extracted through the construction of a protein–protein interaction network. Peripheral myelin protein 22, a major component of myelin in the peripheral nervous system, was used as the query protein. The extracellular domains and regions susceptible to recognition by antibodies were extracted from UniProt. In the study of T cells, linear sequence similarity between H. sapiens proteins and SP was assessed using BLASTp. This study considered the similarity in terms of biochemical groups per residue and affinity to the human major histocompatibility complex (human leukocyte antigen I), which were evaluated using Needle and NetMHCpan 4.1, respectively. Results: A large number of shared pentapeptides between SP and H. sapiens proteins were identified. However, only a small group of 39 proteins was linked to axon and myelin homeostasis. In particular, some proteins, such as phosphacan, attractin, and teneurin-4, were susceptible targets of B and T cells. Other proteins closely related to myelin components in the NS, such as myelin-associated glycoprotein, were found to share at least one pentamer with SP in extracellular domains. Conclusion: Proteins involved in the maintenance of nerve conduction in the central and peripheral NS were identified in H. sapiens. Based on these findings, re-evaluation of the vaccine composition is recommended to prevent possible neurological side effects.

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Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach

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