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bioRxiv · 10.1101/2022.02.18.481028

Furin-cleavage site is present in an antiparallel β-strand in SARS-CoV2 Spike protein

Bashir, A.
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Abstract

Furin cleavage-site (CS) present between the S1/S2 junction in SARS-CoV2 spike (S) protein is critical to drive the fusion of SARS-CoV2 with the host cell. SARS-CoV2 falls in the sarbecovirus lineage that doesnt comprise of furin CS and therefore makes its origin enigmatic. The available wild-type (Wt) SARS-CoV2 S protein with PDB ID: 6yvb lacks a stretch of amino acid including furin CS as well. All investigators till date have shown this stretch existing in the form of a loop. We are for the first time reporting that this stretch comprises of 14 amino acid residues (677QTNSPRRARSVASQ689), forming an antiparallel {beta}-sheet comprising of PRRAR furin CS. We observed the presence of this antiparallel {beta}-sheet in MERS spike protein as well. While switching over from Wt. SARS-CoV2 with PRRAR furin CS to B.1.1.7 variant with HRRAR furin CS, we found 3% increase in the percentage content of {beta} stands. Interestingly, we found that the change of B.1.1.7 to B.1.617 variant comprising of RRRAR furin CS shifted the percentage secondary structure back to that found in Wt. SARS-CoV2. We anticipate that this {beta}-sheet is used as a docking site by host cell proteases to act on furin-CS. Additionally, we studied the interaction of modeled SARS-CoV2 S protein with transmembrane protease, serine 2 (TMPRSS2), and furin proteases, which clearly highlighted that these proteases exclusively uses furin CS located in {beta}-sheet to cleave the SARS-CoV2 S protein at its S1/S2 junction.

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Bashir, A.. 2022-02-18. Furin-cleavage site is present in an antiparallel β-strand in SARS-CoV2 Spike protein. https://doi.org/10.1101/2022.02.18.481028

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