Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System
Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNβ...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/ce14dc80dd234254b629648c94dbb665 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:ce14dc80dd234254b629648c94dbb665 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:ce14dc80dd234254b629648c94dbb6652021-12-01T23:24:58ZStructural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System1664-302X10.3389/fmicb.2021.789062https://doaj.org/article/ce14dc80dd234254b629648c94dbb6652021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.789062/fullhttps://doaj.org/toc/1664-302XMutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNβ production. Mutations have been reported in NSP13; hence, in the current study, biophysical and structural modeling methodologies were adapted to dissect the influence of major mutations in NSP13, i.e., P77L, Q88H, D260Y, E341D, and M429I, on its binding to the TBK1 and to escape the human immune system. The results revealed that these mutations significantly affected the binding of NSP13 and TBK1 by altering the hydrogen bonding network and dynamic structural features. The stability, flexibility, and compactness of these mutants displayed different dynamic features, which are the basis for immune evasion. Moreover, the binding was further validated using the MM/GBSA approach, revealing that these mutations have higher binding energies than the wild-type (WT) NSP13 protein. These findings thus justify the basis of stronger interactions and evasion for these NSP13 mutants. In conclusion, the current findings explored the key features of the NSP13 WT and its mutant complexes, which can be used to design structure-based inhibitors against the SARS-CoV-2 new variants to rescue the host immune system.Farooq RashidMuhammad SulemanAbdullah ShahEmmanuel Enoch DzakahShuyi ChenHaiying WangShixing TangShixing TangShixing TangFrontiers Media S.A.articleSARS-CoV-2NSP13 mutantsTBK1protein-protein dockingMD simulationsMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
SARS-CoV-2 NSP13 mutants TBK1 protein-protein docking MD simulations Microbiology QR1-502 |
| spellingShingle |
SARS-CoV-2 NSP13 mutants TBK1 protein-protein docking MD simulations Microbiology QR1-502 Farooq Rashid Muhammad Suleman Abdullah Shah Emmanuel Enoch Dzakah Shuyi Chen Haiying Wang Shixing Tang Shixing Tang Shixing Tang Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System |
| description |
Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNβ production. Mutations have been reported in NSP13; hence, in the current study, biophysical and structural modeling methodologies were adapted to dissect the influence of major mutations in NSP13, i.e., P77L, Q88H, D260Y, E341D, and M429I, on its binding to the TBK1 and to escape the human immune system. The results revealed that these mutations significantly affected the binding of NSP13 and TBK1 by altering the hydrogen bonding network and dynamic structural features. The stability, flexibility, and compactness of these mutants displayed different dynamic features, which are the basis for immune evasion. Moreover, the binding was further validated using the MM/GBSA approach, revealing that these mutations have higher binding energies than the wild-type (WT) NSP13 protein. These findings thus justify the basis of stronger interactions and evasion for these NSP13 mutants. In conclusion, the current findings explored the key features of the NSP13 WT and its mutant complexes, which can be used to design structure-based inhibitors against the SARS-CoV-2 new variants to rescue the host immune system. |
| format |
article |
| author |
Farooq Rashid Muhammad Suleman Abdullah Shah Emmanuel Enoch Dzakah Shuyi Chen Haiying Wang Shixing Tang Shixing Tang Shixing Tang |
| author_facet |
Farooq Rashid Muhammad Suleman Abdullah Shah Emmanuel Enoch Dzakah Shuyi Chen Haiying Wang Shixing Tang Shixing Tang Shixing Tang |
| author_sort |
Farooq Rashid |
| title |
Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System |
| title_short |
Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System |
| title_full |
Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System |
| title_fullStr |
Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System |
| title_full_unstemmed |
Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System |
| title_sort |
structural analysis on the severe acute respiratory syndrome coronavirus 2 non-structural protein 13 mutants revealed altered bonding network with tank binding kinase 1 to evade host immune system |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/ce14dc80dd234254b629648c94dbb665 |
| work_keys_str_mv |
AT farooqrashid structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT muhammadsuleman structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT abdullahshah structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT emmanuelenochdzakah structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT shuyichen structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT haiyingwang structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT shixingtang structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT shixingtang structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem AT shixingtang structuralanalysisonthesevereacuterespiratorysyndromecoronavirus2nonstructuralprotein13mutantsrevealedalteredbondingnetworkwithtankbindingkinase1toevadehostimmunesystem |
| _version_ |
1718404013706182656 |