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Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera

The genus Betacoronavirus, consisting of four main subgenera (Embecovirus, Merbecovirus, Nobecovirus, and Sarbecovirus), encompasses all clinically significant coronaviruses (CoVs), including SARS, MERS, and the SARS-CoV-2 virus responsible for current COVID-19 pandemic. Very few molecular character...

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Autores principales: Gupta, Radhey S., Khadka, Bijendra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949385/
https://www.ncbi.nlm.nih.gov/pubmed/35327976
http://dx.doi.org/10.3390/genes13030423
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author Gupta, Radhey S.
Khadka, Bijendra
author_facet Gupta, Radhey S.
Khadka, Bijendra
author_sort Gupta, Radhey S.
collection PubMed
description The genus Betacoronavirus, consisting of four main subgenera (Embecovirus, Merbecovirus, Nobecovirus, and Sarbecovirus), encompasses all clinically significant coronaviruses (CoVs), including SARS, MERS, and the SARS-CoV-2 virus responsible for current COVID-19 pandemic. Very few molecular characteristics are known that are specific for the genus Betacoronavirus or its different subgenera. In this study, our analyses of the sequences of four essential proteins of CoVs, viz., spike, nucleocapsid, envelope, and RNA-dependent RNA polymerase (RdRp), identified ten novel molecular signatures consisting of conserved signature indels (CSIs) in these proteins which are specific for the genus Betacoronavirus or its subgenera. Of these CSIs, two 14-aa-conserved deletions found within the heptad repeat motifs 1 and 2 of the spike protein are specific for all betacoronaviruses, except for their shared presence in the highly infectious avian coronavirus. Six additional CSIs present in the nucleocapsid protein and one CSI in the RdRp protein are distinctive characteristics of either the Merbecovirus, Nobecovirus, or Sarbecovirus subgenera. In addition, a 4-aa insert is present in the spike protein, which is uniquely shared by all viruses from the subgenera Merbecovirus, Nobecovirus, and Sarbecovirus, but absent in Embecovirus and all other genera of CoVs. This molecular signature provides evidence that viruses from the three subgenera sharing this CSI are more closely related to each other, and they evolved after the divergence of embecoviruses and other CoVs. As all CSIs specific for different groups of CoVs are flanked by conserved regions, their sequences provide novel means for identifying the above groups of CoVs and for developing novel diagnostic tests. Furthermore, our analyses of the structures of the spike and nucleocapsid proteins show that all identified CSIs are localized in the surface-exposed loops of these protein. It is postulated that these surface loops, through their interactions with other cellular proteins/ligands, play important roles in the biology/pathology of these viruses.
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spelling pubmed-89493852022-03-26 Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera Gupta, Radhey S. Khadka, Bijendra Genes (Basel) Article The genus Betacoronavirus, consisting of four main subgenera (Embecovirus, Merbecovirus, Nobecovirus, and Sarbecovirus), encompasses all clinically significant coronaviruses (CoVs), including SARS, MERS, and the SARS-CoV-2 virus responsible for current COVID-19 pandemic. Very few molecular characteristics are known that are specific for the genus Betacoronavirus or its different subgenera. In this study, our analyses of the sequences of four essential proteins of CoVs, viz., spike, nucleocapsid, envelope, and RNA-dependent RNA polymerase (RdRp), identified ten novel molecular signatures consisting of conserved signature indels (CSIs) in these proteins which are specific for the genus Betacoronavirus or its subgenera. Of these CSIs, two 14-aa-conserved deletions found within the heptad repeat motifs 1 and 2 of the spike protein are specific for all betacoronaviruses, except for their shared presence in the highly infectious avian coronavirus. Six additional CSIs present in the nucleocapsid protein and one CSI in the RdRp protein are distinctive characteristics of either the Merbecovirus, Nobecovirus, or Sarbecovirus subgenera. In addition, a 4-aa insert is present in the spike protein, which is uniquely shared by all viruses from the subgenera Merbecovirus, Nobecovirus, and Sarbecovirus, but absent in Embecovirus and all other genera of CoVs. This molecular signature provides evidence that viruses from the three subgenera sharing this CSI are more closely related to each other, and they evolved after the divergence of embecoviruses and other CoVs. As all CSIs specific for different groups of CoVs are flanked by conserved regions, their sequences provide novel means for identifying the above groups of CoVs and for developing novel diagnostic tests. Furthermore, our analyses of the structures of the spike and nucleocapsid proteins show that all identified CSIs are localized in the surface-exposed loops of these protein. It is postulated that these surface loops, through their interactions with other cellular proteins/ligands, play important roles in the biology/pathology of these viruses. MDPI 2022-02-25 /pmc/articles/PMC8949385/ /pubmed/35327976 http://dx.doi.org/10.3390/genes13030423 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gupta, Radhey S.
Khadka, Bijendra
Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera
title Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera
title_full Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera
title_fullStr Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera
title_full_unstemmed Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera
title_short Conserved Molecular Signatures in the Spike, Nucleocapsid, and Polymerase Proteins Specific for the Genus Betacoronavirus and Its Different Subgenera
title_sort conserved molecular signatures in the spike, nucleocapsid, and polymerase proteins specific for the genus betacoronavirus and its different subgenera
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949385/
https://www.ncbi.nlm.nih.gov/pubmed/35327976
http://dx.doi.org/10.3390/genes13030423
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