The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade

Abstract

In 2019, a new coronavirus (2019-nCoV) infecting Humans has emerged in Wuhan, China. Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV and SARS-like CoVs, we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site in the viral cycle, pathogenicity and its potential implication in the development of antivirals.

Keywords: 2019-nCoV; Antivirals; Furin; Maturation protease; SARS-CoV; Spike protein.

Fig. 1

Characterization of an nCoV-peculiar sequence at the S1/S2 cleavage site in the S-protein sequence, compared SARS-like CoV. (A) Phylogenetic tree of selected coronaviruses from genera alphacoronavirus (α-Cov) and betacoronavirus (β-CoV), lineages a, b, c and d: 2019-nCoV (NC_045512.2), CoV-ZXC21 (MG772934), SARS-CoV (NC_004718.3), SARS-like BM4821 (MG772934), HCoV-OC43 (AY391777), HKU9-1 (EF065513), HCoV-NL63 (KF530114.1), HCoV229E (KF514433.1), MERS-CoV (NC019843.3), HKU1 (NC_006577.2). The phylogenetic tree was obtained on the Orf1ab amino acid sequence using the Maximum Likelihood method by Mega X software. Red asterisks indicate the presence of a canonical furin-like cleavage motif at site 1; (B) Alignment of the coding and amino acid sequences of the S-protein from CoV-ZXC21 and 2019-nCoV at the S1/S2 site. The 2019-nCoV-specific sequence is in bold. The sequence of CoV-ZXC21 S-protein at this position is representative of the sequence of the other betacoronaviruses belonging to lineage b, except the one of 2019-nCoV. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Schematic representation of the human 2019-nCoV S-protein with a focus on the putative maturation sites. The domains were previously characterized in SARS-CoV and MERS-CoV: Signal peptide (SP), N-terminal domain (NTD), receptor-binding domain (RBD), fusion peptide (FP), internal fusion peptide (IFP), heptad repeat 1/2 (HR1/2), and the transmembrane domain (TM). The SP, S1↓S2 and S2′ cleavage sites are indicated by arrows. The sequence of different CoV S1/S2 and S2′ cleavage sites were aligned using Multalin webserver (http://multalin.toulouse.inra.fr/multalin/) with manual adjustments and the figure prepared using ESPript 3 (http://espript.ibcp.fr/ESPript/ESPript/) presenting the secondary structure of SARS-CoV S-protein at the bottom of the alignment (PDB 5X58) (Yuan et al., 2017). Insertion of furin like cleavage site is surrounded by a black frame. Red asterisks indicate the presence of a canonical furin-like cleavage motif at the S1/S2 site. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)