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. 2022 Feb 21;38(10):110503. doi: 10.1016/j.celrep.2022.110503

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© 2022 The Author(s)

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SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide

(A–C) In silico prediction of HLA-E^∗01:01-binding nonamers using NetMHC4.0. (A) pp65 protein containing the irrelevant pp65_495–503 peptide. (B) HLA-C^∗01:02 protein containing the known stabilizing HLA-C_3–11 peptide. (C) SARS-CoV-2 ORFeome (isolate Wuhan-Hu-1) containing the three top candidates Nsp13_232–240, Nsp6_114–122, and S_269–277.

(D) HLA-E stabilization on K562/HLA-E after pulsing with the indicated peptides at 300 μM overnight in serum-free medium. Left: representative HLA-E surface detection by flow cytometry (black line: solvent control; back filled histogram: pp65_495-503; blue filled histogram: HLA-C_3-11; red filled histogram: Nsp13_232-240). Right: summary of HLA-E stabilization as geometric mean fluorescence intensity (geoMFI; n = 3 independent experiments).

(E) HLA-E surface stabilization after peptide pulsing with varying concentrations (n = 4 independent experiments).

(F) Pulse chase of HLA-E surface levels normalized to initiation of chase (t₀; n = 4 independent experiments).

(G) Summary table of delta energy of binding as indicator of theoretical affinity of HLA-E/peptide complexes determined by molecular dynamics (MD) simulations (n = 3 replicate simulations).

(H) MD-based positioning of peptides in the peptide-binding groove of HLA-E. Left: HLA-C_3–11. Right: Nsp13_232–240.

(I) Phylogenetic relationships between the genomes of SARS-CoV-2, SARS-CoV-1, and common cold-causing HCoVs as determined by Clustalω. Scale bar indicates nucleotide substitution per site.

(J) Sequence identities relative to SARS-CoV-2. Left: genome level as determined by Clustalω. Middle: ORF1ab protein level as determined by Clustalω. Right: Nsp13_232–240 peptide identity.

(K) Nsp13_232–240 amino acid sequence comparison between viruses. Sequence alterations relative to SARS-CoV-2 are highlighted in red.

(L) HLA-E surface stabilization on K562/HLA-E after pulsing with Nsp13_232–240 peptides from different viruses at 300 μM overnight determined by flow cytometry and displayed as geoMFI (n = 3 independent experiments).

Data are either mean and individual data points (D) or mean ± SD (E, F, G, and L). Statistical significance was tested using two-way repeated measures ANOVA with Bonferroni correction (E and F).

^∗p < 0.05. See also Figure S1.