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Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach

Dipeptidyl peptidase 4 (DPP4) has been identified as the main receptor of MERS-CoV facilitating its cellular entry and enhancing its viral replication upon the emergence of this novel coronavirus. DPP4 receptor is highly conserved among many species, but the genetic variability among direct binding...

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Autores principales: Abbad, Anass, Anga, Latifa, Faouzi, Abdellah, Iounes, Nadia, Nourlil, Jalal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516309/
https://www.ncbi.nlm.nih.gov/pubmed/34648601
http://dx.doi.org/10.1371/journal.pone.0258750
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author Abbad, Anass
Anga, Latifa
Faouzi, Abdellah
Iounes, Nadia
Nourlil, Jalal
author_facet Abbad, Anass
Anga, Latifa
Faouzi, Abdellah
Iounes, Nadia
Nourlil, Jalal
author_sort Abbad, Anass
collection PubMed
description Dipeptidyl peptidase 4 (DPP4) has been identified as the main receptor of MERS-CoV facilitating its cellular entry and enhancing its viral replication upon the emergence of this novel coronavirus. DPP4 receptor is highly conserved among many species, but the genetic variability among direct binding residues to MERS-CoV restrained its cellular tropism to humans, camels and bats. The occurrence of natural polymorphisms in human DPP4 binding residues is not well characterized. Therefore, we aimed to assess the presence of potential mutations in DPP4 receptor binding domain (RBD) among a population highly exposed to MERS-CoV in Morocco and predict their effect on DPP4 –MERS-CoV binding affinity through a computational approach. DPP4 synonymous and non-synonymous mutations were identified by sanger sequencing, and their effect were modelled by mutation prediction tools, docking and molecular dynamics (MD) simulation to evaluate structural changes in human DPP4 protein bound to MERS-CoV S1 RBD protein. We identified eight mutations, two synonymous mutations (A291 =, R317 =) and six non-synonymous mutations (N229I, K267E, K267N, T288P, L294V, I295L). Through docking and MD simulation techniques, the chimeric DPP4 –MERS-CoV S1 RBD protein complex models carrying one of the identified non-synonymous mutations sustained a stable binding affinity for the complex that might lead to a robust cellular attachment of MERS-CoV except for the DPP4 N229I mutation. The latter is notable for a loss of binding affinity of DPP4 with MERS-CoV S1 RBD that might affect negatively on cellular entry of the virus. It is important to confirm our molecular modelling prediction with in-vitro studies to acquire a broader overview of the effect of these identified mutations.
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spelling pubmed-85163092021-10-15 Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach Abbad, Anass Anga, Latifa Faouzi, Abdellah Iounes, Nadia Nourlil, Jalal PLoS One Research Article Dipeptidyl peptidase 4 (DPP4) has been identified as the main receptor of MERS-CoV facilitating its cellular entry and enhancing its viral replication upon the emergence of this novel coronavirus. DPP4 receptor is highly conserved among many species, but the genetic variability among direct binding residues to MERS-CoV restrained its cellular tropism to humans, camels and bats. The occurrence of natural polymorphisms in human DPP4 binding residues is not well characterized. Therefore, we aimed to assess the presence of potential mutations in DPP4 receptor binding domain (RBD) among a population highly exposed to MERS-CoV in Morocco and predict their effect on DPP4 –MERS-CoV binding affinity through a computational approach. DPP4 synonymous and non-synonymous mutations were identified by sanger sequencing, and their effect were modelled by mutation prediction tools, docking and molecular dynamics (MD) simulation to evaluate structural changes in human DPP4 protein bound to MERS-CoV S1 RBD protein. We identified eight mutations, two synonymous mutations (A291 =, R317 =) and six non-synonymous mutations (N229I, K267E, K267N, T288P, L294V, I295L). Through docking and MD simulation techniques, the chimeric DPP4 –MERS-CoV S1 RBD protein complex models carrying one of the identified non-synonymous mutations sustained a stable binding affinity for the complex that might lead to a robust cellular attachment of MERS-CoV except for the DPP4 N229I mutation. The latter is notable for a loss of binding affinity of DPP4 with MERS-CoV S1 RBD that might affect negatively on cellular entry of the virus. It is important to confirm our molecular modelling prediction with in-vitro studies to acquire a broader overview of the effect of these identified mutations. Public Library of Science 2021-10-14 /pmc/articles/PMC8516309/ /pubmed/34648601 http://dx.doi.org/10.1371/journal.pone.0258750 Text en © 2021 Abbad et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Abbad, Anass
Anga, Latifa
Faouzi, Abdellah
Iounes, Nadia
Nourlil, Jalal
Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach
title Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach
title_full Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach
title_fullStr Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach
title_full_unstemmed Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach
title_short Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach
title_sort effect of identified non-synonymous mutations in dpp4 receptor binding residues among highly exposed human population in morocco to mers-cov through computational approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516309/
https://www.ncbi.nlm.nih.gov/pubmed/34648601
http://dx.doi.org/10.1371/journal.pone.0258750
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