Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2
The ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2) of the host cells. Therefore, understanding the fund...
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doaj-505659ad3f494725b6edf8236ecf101f2020-12-09T05:33:02ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-12-01710.3389/fmolb.2020.591873591873Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2Yixin Xie0Chitra B. Karki1Dan Du2Haotian Li3Jun Wang4Adebiyi Sobitan5Shaolei Teng6Qiyi Tang7Lin Li8Lin Li9Computational Science Program, University of Texas at El Paso, El Paso, TX, United StatesComputational Science Program, University of Texas at El Paso, El Paso, TX, United StatesComputational Science Program, University of Texas at El Paso, El Paso, TX, United StatesDepartment of Physics, University of Texas at El Paso, El Paso, TX, United StatesDepartment of Physics, University of Texas at El Paso, El Paso, TX, United StatesDepartment of Biology, Howard University, Washington, DC, United StatesDepartment of Biology, Howard University, Washington, DC, United StatesDepartment of Biology, Howard University, Washington, DC, United StatesComputational Science Program, University of Texas at El Paso, El Paso, TX, United StatesDepartment of Physics, University of Texas at El Paso, El Paso, TX, United StatesThe ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2) of the host cells. Therefore, understanding the fundamental mechanisms of how SARS-CoV-2 S protein receptor binding domain (RBD) binds to ACE2 is highly demanded for developing treatments for COVID-19. Here we implemented multi-scale computational approaches to study the binding mechanisms of human ACE2 and S proteins of both SARS-CoV and SARS-CoV-2. Electrostatic features, including electrostatic potential, electric field lines, and electrostatic forces of SARS-CoV and SARS-CoV-2 were calculated and compared in detail. The results demonstrate that SARS-CoV and SARS-CoV-2 S proteins are both attractive to ACE2 by electrostatic forces even at different distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS-CoV S protein and SARS-CoV-2 S protein. Such differences are analyzed comprehensively. Compared to SARS-CoV, the SARS-CoV-2 binds with ACE2 using a more robust strategy: The electric field line related residues are distributed quite differently, which results in a more robust binding strategy of SARS-CoV-2. Also, SARS-CoV-2 has a higher electric field line density than that of SARS-CoV, which indicates stronger interaction between SARS-CoV-2 and ACE2, compared to that of SARS-CoV. Key residues involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID-19.https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/fullACE2angiotensin-converting enzyme 2protein- protein interactionsmolecular dynamicspike proteinSARS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yixin Xie Chitra B. Karki Dan Du Haotian Li Jun Wang Adebiyi Sobitan Shaolei Teng Qiyi Tang Lin Li Lin Li |
spellingShingle |
Yixin Xie Chitra B. Karki Dan Du Haotian Li Jun Wang Adebiyi Sobitan Shaolei Teng Qiyi Tang Lin Li Lin Li Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 Frontiers in Molecular Biosciences ACE2 angiotensin-converting enzyme 2 protein- protein interactions molecular dynamic spike protein SARS |
author_facet |
Yixin Xie Chitra B. Karki Dan Du Haotian Li Jun Wang Adebiyi Sobitan Shaolei Teng Qiyi Tang Lin Li Lin Li |
author_sort |
Yixin Xie |
title |
Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 |
title_short |
Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 |
title_full |
Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 |
title_fullStr |
Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 |
title_full_unstemmed |
Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 |
title_sort |
spike proteins of sars-cov and sars-cov-2 utilize different mechanisms to bind with human ace2 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2020-12-01 |
description |
The ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2) of the host cells. Therefore, understanding the fundamental mechanisms of how SARS-CoV-2 S protein receptor binding domain (RBD) binds to ACE2 is highly demanded for developing treatments for COVID-19. Here we implemented multi-scale computational approaches to study the binding mechanisms of human ACE2 and S proteins of both SARS-CoV and SARS-CoV-2. Electrostatic features, including electrostatic potential, electric field lines, and electrostatic forces of SARS-CoV and SARS-CoV-2 were calculated and compared in detail. The results demonstrate that SARS-CoV and SARS-CoV-2 S proteins are both attractive to ACE2 by electrostatic forces even at different distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS-CoV S protein and SARS-CoV-2 S protein. Such differences are analyzed comprehensively. Compared to SARS-CoV, the SARS-CoV-2 binds with ACE2 using a more robust strategy: The electric field line related residues are distributed quite differently, which results in a more robust binding strategy of SARS-CoV-2. Also, SARS-CoV-2 has a higher electric field line density than that of SARS-CoV, which indicates stronger interaction between SARS-CoV-2 and ACE2, compared to that of SARS-CoV. Key residues involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID-19. |
topic |
ACE2 angiotensin-converting enzyme 2 protein- protein interactions molecular dynamic spike protein SARS |
url |
https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full |
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