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Fig 1.

Graphic summary of ORF7a-VKORC1 interaction and possible effects.

The interaction between ORF7a and VKORC1 and possible effects of this interaction.

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Table 1.

Sequence homology of selected SARS and SARS-CoV-2 proteins.

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Table 1 Expand

Table 2.

Possible predicted effect of variants in VKORC, SERPING1 and PABPC4.

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Table 2 Expand

Table 3.

Population frequencies (gnomAD) of GWAS variants of VKORC1, SERPING1, and PABPC4.

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Table 3 Expand

Fig 2.

Predicted dock of VKORC1 and ORF7a transmembrane domain.

A. Five protein-protein docks depict one main binding site (teal, grey, yellow, green, blue). B. The lowest interface-energy model is shown as a surface representation. C. The lowest interface-energy model, with side chains shown in wheat for amino acids at the interface. D. Another view of the lowest interface-energy model, with side chains shown in wheat at the interface and hydrophobics shown in blue. Amino acids of VKORC1 necessary for vitamin K binding (83F, 80N, 135C, 55F) or warfarin binding (134V, 133I) are given in green.

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Fig 3.

Plots of interface energy (I_sc) against interface root mean square error (I_rms).

Each point represents a complex formed from one of the top 5 ZDock outputs of VKORC1 and ORF7a proteins, using 10,000 decoys. All plots form energy funnels.

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Fig 3 Expand

Table 4.

Variations’ clinical impact.

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Table 4 Expand

Fig 4.

Locations of warfarin dosage affecting nonsynonymous variants in VKORC1.

VKORC1 is shown in salmon, while ORF7a is shown in grey. Warfarin dosage affecting nonsynonymous variants are shown in blue. Active site amino acids are shown in green.

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Fig 4 Expand

Table 5.

Population frequencies of missense and synonymous VKORC1 variants.

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Table 5 Expand

Fig 5.

Structural alignment of ORF7a, CXADR, and PCDH1 proteins.

The alignment is largely confined to the beta sheets.

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Fig 5 Expand