tetano
Editor, Senior Moderator
Comput Struct Biotechnol J
. 2020 Nov 12.
doi: 10.1016/j.csbj.2020.11.002. Online ahead of print.
Mutations in the SARS-CoV-2 Spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization
Masaud Shah[SUP] 1 [/SUP], Bilal Ahmad[SUP] 2 [/SUP], Sangdun Choi[SUP] 2 [/SUP], Hyun Goo Woo[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (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.
Keywords: COVID-19; SARS-CoV-2; mAb; spike protein; therapeutic peptides.
. 2020 Nov 12.
doi: 10.1016/j.csbj.2020.11.002. Online ahead of print.
Mutations in the SARS-CoV-2 Spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization
Masaud Shah[SUP] 1 [/SUP], Bilal Ahmad[SUP] 2 [/SUP], Sangdun Choi[SUP] 2 [/SUP], Hyun Goo Woo[SUP] 1 [/SUP]
Affiliations
- PMID: 33200028
- PMCID: PMC7657873
- DOI: 10.1016/j.csbj.2020.11.002
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (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.
Keywords: COVID-19; SARS-CoV-2; mAb; spike protein; therapeutic peptides.