| dc.description | Background: The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in
Wuhan (China) in December of 2019 is responsible for the current global pandemic. Phylogenetic analysis revealed
that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV.
Its genome is ∼ 30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode
for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important
pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and
hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro
reconstitution studies determined that the mechanisms of action are mediated by (a) the presence of specific amino
acid residues of nsp1 and (b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution
of certain amino acids resulted in reduction of its negative effects.
Methods: A total of 17,928 genome sequences were obtained from the GISAID database (December 2019 to July
2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed
using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST.
Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.
Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion
of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in
different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.
Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests
that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral
replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from
nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe
indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: (i) confirm the spreading of
this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of
asymptomatic and pauci-symptomatic subjects, and (ii) correlate these changes in nsp1 with potential decreased viral
pathogenicity. | |
