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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Main Authors: Masaud Shah, Bilal Ahmad, Sangdun Choi, Hyun Goo Woo
Format: Article
Language:English
Published: Elsevier 2020-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
mAb
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037020304694
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spelling 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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