Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a novel beta coronavirus. SARS-CoV-2 uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 rai...
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doaj-b2d606cdf1344b0aaced60ef553b00f82021-01-02T05:09:17ZengElsevierComputational and Structural Biotechnology Journal2001-03702020-01-011834023414Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralizationMasaud Shah0Bilal Ahmad1Sangdun Choi2Hyun Goo Woo3Department of Physiology, Ajou University School of Medicine, Suwon, Republic of KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon, Republic of KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon, Republic of KoreaDepartment of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea; Corresponding author at: Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Republic of Korea.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a novel beta coronavirus. SARS-CoV-2 uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike-ACE2 binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2-binding. Pro-to-Ala475 substitution and Gly482 insertion in the AGSTPCNGV-loop of RBD possibly hinders neutralization of SARS-CoV-2 by anti-SARS-CoV mAbs. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of effective neutralizing agents.http://www.sciencedirect.com/science/article/pii/S2001037020304694COVID-19mAbSARS-CoV-2Spike proteinTherapeutic peptides |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Masaud Shah Bilal Ahmad Sangdun Choi Hyun Goo Woo |
spellingShingle |
Masaud Shah Bilal Ahmad Sangdun Choi Hyun Goo Woo Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization Computational and Structural Biotechnology Journal COVID-19 mAb SARS-CoV-2 Spike protein Therapeutic peptides |
author_facet |
Masaud Shah Bilal Ahmad Sangdun Choi Hyun Goo Woo |
author_sort |
Masaud Shah |
title |
Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization |
title_short |
Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization |
title_full |
Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization |
title_fullStr |
Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization |
title_full_unstemmed |
Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization |
title_sort |
mutations in the sars-cov-2 spike rbd are responsible for stronger ace2 binding and poor anti-sars-cov mabs cross-neutralization |
publisher |
Elsevier |
series |
Computational and Structural Biotechnology Journal |
issn |
2001-0370 |
publishDate |
2020-01-01 |
description |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a novel beta coronavirus. SARS-CoV-2 uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike-ACE2 binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2-binding. Pro-to-Ala475 substitution and Gly482 insertion in the AGSTPCNGV-loop of RBD possibly hinders neutralization of SARS-CoV-2 by anti-SARS-CoV mAbs. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of effective neutralizing agents. |
topic |
COVID-19 mAb SARS-CoV-2 Spike protein Therapeutic peptides |
url |
http://www.sciencedirect.com/science/article/pii/S2001037020304694 |
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