Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules

Loubna Allam; Fatima Ghrifi; Hakmi Mohammed; Naima El Hafidi; Rachid El Jaoudi; Jaouad El Harti; Badreddine Lmimouni; Lahcen Belyamani; Azeddine Ibrahimi

doi:10.1177/1177932220965505

Figure 4.

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Object name is 10.1177_1177932220965505-fig4.jpg

Modes of polyphenols binding on the GRP78 site. The active site in GRP78 is colored orange in (a′, b′, c′, and d′). The 4 compounds established multiple hydrogen bonds with the residues at the active site of GRP78. All the compounds interacted with the Glu-427 residue, and other interactions were observed with Ser-455, Ser-452, Ile-450, Ala-454, Gln-458 for EGCG (a, a′). Homoeriodictyol (b, b′) interacted with Gly-430, Ile-450, and Val-429; isorhamnetin (c, c′) interacted with Gly-430, Ser-448, and Gln-458; and curcumin (d, d′) interacted with Ser-425, Ile-450, and Thr-441. The best affinity was attributed to EGCG (–10.5 kcal/mol). EGCG interacts through the H bonds with Glu-427, Gln-458, Ser-455, Ala-454 and a hydrophobic bond with Ile-450; homoeriodictyol and isorhamnetin establish the same H bonds with Glu-427, Glu-430, Ser-448, and Gln-485; curcumine interact with 2 residues Glu-427 and Ile-450 through the H bonds and 2 hydrophobic bonds through Ser-425 and Thr-441. EGCG indicates epigallocatechin gallate; GRP78, glucose-regulating protein 78.