Abstract
The serine proteases neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), and neutrophil serine protease 4 (NSP4) are secreted by activated neutrophils as a part of the innate immune response against invading pathogens. However, these serine proteases might be adopted by viruses to mediate viral surface protein priming resulting in host cell entrance and productive infection. Indeed, NE and PR3 hydrolyze the scissile peptide bond within the proteolytically sensitive polybasic sequence of the activation loop of SARS-CoV-2 located at the S1/S2 interface of the Spike (S) protein; an amino acid motif which differs from SARS-CoV-1. The occurrence of novel SARS-CoV-2 variants and substitution of distinct amino acids at the polybasic sequence prompts serious concerns regarding increased transmissibility. We propose that a novel cleavage site by CatG of the Omicron variant and the increased substrate turnover of the Delta variant by furin within the polybasic sequence should be considered for increased transmission of SARS-CoV-2 variants.
【초록키워드】 SARS-CoV-2, innate immune response, furin, neutrophil, variant, SARS-CoV-2 variant, Infection, peptide, omicron, delta variant, SARS-CoV-1, variants, Protein, Transmissibility, SARS-CoV-2 variants, amino acids, Omicron variant, Pathogens, Neutrophil elastase, Amino acid, Activated neutrophils, host cell, Activation, Serine, viral surface, sequence, S1/S2, Substitution, cleavage site, priming, serine protease, invading pathogens, proteinase, motif, transmission of SARS-CoV-2, serine proteases, nsp4, Peptide bond, Occurrence, resulting, virus, adopted, the Spike, activated neutrophil, polybasic, secreted, 【제목키워드】 omicron, P681H, Activation, sequence, cleavage site, amino acid substitution, the spike protein, polybasic, the SARS-CoV-2,