An exclusive 42 amino acid signature in pp1ab protein provides insights into the evolutive history of the 2019 novel human-pathogenic coronavirus (SARS-CoV-2)

Abstract

The city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS-CoV-2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic-structural sequence analysis of pp1ab protein of SARS-CoV-2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS-CoV-2 (AS-SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS-SCoV2 located in the acidic-domain of papain-like protein of SARS-CoV-2 and bat-SL-CoV-RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat-SL-CoV-RaTG13. The implication of this amino acid signature in papain-like protein structure arrangement and function is something worth to be explored.

Keywords: SARS; SARS-CoV-2; Wuhan; coronavirus; pp1ab protein; virus.

Figure 1

Alignment of pp1ab proteins from sarbecoviruses. Pp1ab proteins of sarbecoviruses (green: clade 1; blue clade 2: blue; clade 3: red) were aligned using the multiple sequence alignment program MAFFT v7 and manually edited for maximizing coincidences. The figure shows the AC domain of pp1ab. Conserved residues are yellow highlighted. AS‐SCoV2 conserved residues are blue highlighted. N‐terminal region of the papain‐like protein is represented above the alignment. AS‐SCoV2, SARS‐CoV‐2; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 2

Phylogenetic analysis of SARS‐CoV‐2. The Phylogenetic relationship was inferred with the Neighbor‐Joining method based on the genome alignment. Bootstrap values (5000 iterations) are indicated for each node. Dots represent the clade 1 (green), clade 2 (blue), and clade 3 (red). Star indicates the probable acquisition of ancestral AS‐SCoV2. The evolutionary distances were computed using the number of differences method. The scale bar, placed below the tree, indicates the number of base differences per sequence. AS‐SCoV2, SARS‐CoV‐2; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2