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. 2022 Mar 29;14(2):243-249.
doi: 10.3390/idr14020029.

Conservation and Enhanced Binding of SARS-CoV-2 Omicron Spike Protein to Coreceptor Neuropilin-1 Predicted by Docking Analysis

Piyush Baindara  1 , Dinata Roy  2 , Santi M Mandal  3 , Adam G Schrum  1
Affiliations

Conservation and Enhanced Binding of SARS-CoV-2 Omicron Spike Protein to Coreceptor Neuropilin-1 Predicted by Docking Analysis

Piyush Baindara et al. Infect Dis Rep. .

Abstract

The Omicron variant of SARS-CoV-2 bears peptide sequence alterations that correlate with a higher infectivity than was observed in the original SARS-CoV-2 isolated from Wuhan, China. We analyzed the CendR motif of spike protein and performed in silico molecular docking with neuropilin-1 (Nrp1), a receptor-ligand interaction known to support infection by the original variant. Our analysis predicts conserved and slightly increased energetic favorability of binding for Omicron CendR:Nrp1. We propose that the viral spike:Nrp1 coreceptor pathway may contribute to the infectivity of the Omicron variant of SARS-CoV-2.

Keywords: COVID-19; CendR; Omicron; SARS-CoV-2; neuropilin-1; spike protein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
NRP1 as a coreceptor for SARS-CoV-2 infection. (A) ACE2, Nrp1, and TMPRSS2 proteins and color code-matched binding sites on spike protein domains are illustrated. The amino acid sequence of the CendR motif of the S1 domain of spike protein is shown for Omicron, where sequences altered relative to the original Wuhan variant are highlighted in yellow. The red arrowhead indicates the furin protease cleavage site that generates S1 and S2. NTD: N-terminal domain; RBD: Receptor Binding Domain; HR1 and HR2: Heptad repeats; TM: Transmembrane domain; CT: Cytoplasmic domain. (B,C) Data from Human Protein Atlas display tissue expression of (B) ACE2 and (C) Nrp1. Red asterisks (*) represent major infection sites of SARS-CoV-2, where both ACE2 and Nrp1 are co-expressed.
Figure 2
Figure 2
Homology modeling, sequence analysis for variant amino acids, and molecular docking analysis of CendR motif of original Wuhan isolate or Omicron variant with Nrp1. (A) CendR motif of original Wuhan isolate of SARS-CoV-2. (B) CendR motif of Omicron with amino acids that are altered with respect to the original Wuhan variant shown in red. (C) Sequence alignment of CendR motifs from the original Wuhan isolate versus Omicron variant with amino acid alterations highlighted in yellow. (D) Nrp1 docking with CendR motif of original Wuhan isolate. (E) Nrp1 docking with CendR motif of Omicron variant. Interactions are shown in the zoomed image while the b1 domain (yellow color) contains the interaction site for the CendR motifs.
See this image and copyright information in PMC

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