SARS-CoV-2 spike evolutionary behaviors; simulation of N501Y mutation outcomes in terms of immunogenicity and structural characteristic.
J Cell Biochem
; 123(2): 417-430, 2022 02.
Article
in English
| MEDLINE | ID: covidwho-1525444
ABSTRACT
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a large number of mutations in its genome have been reported. Some of the mutations occur in noncoding regions without affecting the pathobiology of the virus, while mutations in coding regions are significant. One of the regions where a mutation can occur, affecting the function of the virus is at the receptor-binding domain (RBD) of the spike protein. RBD interacts with angiotensin-converting enzyme 2 (ACE2) and facilitates the entry of the virus into the host cells. There is a lot of focus on RBD mutations, especially the displacement of N501Y which is observed in the UK/Kent, South Africa, and Brazilian lineages of SARS-CoV-2. Our group utilizes computational biology approaches such as immunoinformatics, protein-protein interaction analysis, molecular dynamics, free energy computation, and tertiary structure analysis to disclose the consequences of N501Y mutation at the molecular level. Surprisingly, we discovered that this mutation reduces the immunogenicity of the spike protein; also, displacement of Asn with Tyr reduces protein compactness and significantly increases the stability of the spike protein and its affinity to ACE2. Moreover, following the N501Y mutation secondary structure and folding of the spike protein changed dramatically.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Point Mutation
/
Mutation, Missense
/
Pandemics
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
J Cell Biochem
Year:
2022
Document Type:
Article
Affiliation country:
Jcb.30181
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