Recognition of gluconeogenic enzymes; Icl1, Fbp1, and Mdh2 by Gid4 ligase: A molecular docking study

Biochemical and Biophysical Research Communications

Elgohary

2021

Self Cite

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.

Section: Methodsmentioning

confidence: 99%

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

Elgohary

2021

Self Cite

“…The CHARMM36 force field is used, while the TIP3P water model is utilized in the simulation using NAMD 2.13 software (12,13). Different in-house written scripts and the visualizing molecular dynamics (VMD) software tools are being used in data analysis (14,15).…”

Section: Figure 1 (A) the Superposition Of The Docked Complexes Of Grmentioning

confidence: 99%

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

Elgohary

2021

Preprint

Self Cite

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.

“…TIP3P water model is used in the system simulation using NAMD 2.13 software (7). Different in-house scripts and the visualizing molecular dynamics (VMD) software tools are used to analyze data (8,9).…”

Section: E484 K31mentioning

confidence: 99%

Host-cell recognition through GRP78 is enhanced in the new UK variant of SARS-CoV-2, in silico 

2021

Preprint

Self Cite

New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H). The N501Y lies in the receptor-binding domain (RBD) of the spike and interacts with the host-cell receptor ACE2 responsible for viral recognition and entry. We tried to simulate the system of ACE2-SARS-CoV-2 spike RBD in the wildtype and mutated isoform of the RBD (N501Y). Additionally, the GRP78 association with the ACE2-SARS-CoV-2 spike RBD is modeled at the presence of this mutant variant of the viral spike.