Host-cell recognition through GRP78 is enhanced in the new variants of SARS-CoV-2; in silico perspective

Abstract

New SARS-CoV-2 variants started in the UK and South Africa in December 2020 and currently spreading worldwide during the last few days. Additionally, another more recent variant sparked in Brazil (B.1.1.248 lineage) this month. The new variant 501.V2 (South African) bears three mutations in the receptor-binding domain (RBD) of the spike glycoprotein, K417N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage have 12 mutations. The N501Y mutation is found in South African and Brazilian variants and is also shared with the UK variant VOC-202012/01 (1). This mutation may affect the host-cell receptor ACE2 (angiotensin-converting enzyme 2) recognition (2). Despite its presence in the ACE2 binding surface, we showed that the N501Y mutant shows a remarkable increase in binding of the ACE2-RBD complex to the host-cell surface Glucose Regulated Protein 78 (CS-GRP78) (3). On the other hand, the E484K is found in the spike RBD's binding motif that we reported earlier to be recognized by cell-surface GRP78 (C480-C488 region of the spike) (4). In this study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wildtype and mutated (K417N, E484K, and N501Y) isoforms. Additionally, the CS-GRP78 association with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-RBD) is modeled at the presence of these mutant variants of the viral spike.

Role of COVID 19 Inflammatory Markers in Rhino-Orbito-Cerebral Mucormycosis: A Case Study in Predisposed Patients at a Designated Nodal Centre

“…Ibrahim et al [ 17 ] and others have reported that glucose related protein 78 (GRP78) could act as an alternative route for virus entry. It is noted mucor fungus also has the same port of entry i.e., GRP78 into nasal and paranasal sinus mucosa through its coat protein spore coat protein homologue (CotH3 [ 24 ]. In COVID-19 infection there is an increased expression of GRP78 making the cells vulnerable to fungal pathogens [ 17 , 25 ].…”

Persistence of humoral immune response to SARS-CoV-2 up to 7 months post-infection: Cross-sectional study, South India, 2020–21

“…All 40 vaccinated HCWs who were infected before July 2020 had higher neutralizing antibody titers in April 2021 than in July 2020. The neutralizing antibody titers for April 2021 were also much higher than those for July 2020 (median 16, IQR [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], Fig. 1 B), regardless of the number of doses given ( p < 0.01; Wilcoxon signed rank tests).…”

Interference of Chaga mushroom terpenoids with the attachment of SARS-CoV-2; in silico perspective

“…Therefore, we think that the administration of Chaga mushroom terpenoids would be safe with minimal or no side effects, but yet to be verified experimentally. The recognition of SARS-CoV-2 spike by the cell-surface GRP78 became significantly evident in the latest virus variants, the UK (VOC-202012/01), the South African (501.V2), and the Brazilian (B.1.1.248 lineage) in addition to Omicron variants [ [68] , [69] , [70] ]. Three potential mutations in the SARS-CoV-2 spike were reported in these new variants of the virus (K417N, E484K, and N501Y).…”