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Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective.
Biochem Biophys Res Commun. 2021 07 12; 562:89-93.BB

Abstract

New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell.

Authors+Show Affiliations

Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt. Electronic address: abdo@sci.cu.edu.eg.Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34049205

Citation

Ibrahim, Ibrahim M., et al. "Recognition Through GRP78 Is Enhanced in the UK, South African, and Brazilian Variants of SARS-CoV-2; an in Silico Perspective." Biochemical and Biophysical Research Communications, vol. 562, 2021, pp. 89-93.
Ibrahim IM, Elfiky AA, Elgohary AM. Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective. Biochem Biophys Res Commun. 2021;562:89-93.
Ibrahim, I. M., Elfiky, A. A., & Elgohary, A. M. (2021). Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective. Biochemical and Biophysical Research Communications, 562, 89-93. https://doi.org/10.1016/j.bbrc.2021.05.058
Ibrahim IM, Elfiky AA, Elgohary AM. Recognition Through GRP78 Is Enhanced in the UK, South African, and Brazilian Variants of SARS-CoV-2; an in Silico Perspective. Biochem Biophys Res Commun. 2021 07 12;562:89-93. PubMed PMID: 34049205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective. AU - Ibrahim,Ibrahim M, AU - Elfiky,Abdo A, AU - Elgohary,Alaa M, Y1 - 2021/05/21/ PY - 2021/05/07/received PY - 2021/05/17/accepted PY - 2021/5/29/pubmed PY - 2021/6/22/medline PY - 2021/5/28/entrez KW - 501.V2 KW - B.1.1.248 lineage KW - GRP78 KW - SARS-CoV-2 KW - Spike RBD KW - Structural bioinformatics SP - 89 EP - 93 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 562 N2 - New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/34049205/Recognition_through_GRP78_is_enhanced_in_the_UK_South_African_and_Brazilian_variants_of_SARS_CoV_2 DB - PRIME DP - Unbound Medicine ER -