Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy

Abstract

Background: SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection.

Methods: A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection.

Finding: We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures.

Interpretation: One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.

Keywords: Autophagy; Bio-informatic; COVID-19; Coronavirus; Molecular evolution; SARS-CoV-2.

Fig. 1

I-TASSER model of NSP6. Residue under positive selective pressure with a p< 0.05 is shown as a sphere. Residues found in the structure proximity are shown in sticks. All residues are marked by the corresponding labels.

Fig. 2

Results obtained with Protter and TMHMM are shown in panel A and B, respectively. In the panel A, the residue under positive pressure with p< 0.05 is marked by the red arrow (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).