Emerging genetic diversity among clinical isolates of SARS-CoV-2: Lessons for today

Abstract

Considering the current pandemic of COVID-19, it is imperative to gauge the role of molecular divergence in SARS-CoV-2 with time, due to clinical and epidemiological concerns. Our analyses involving molecular phylogenetics is a step toward understanding the transmission clusters that can be correlated to pathophysiology of the disease to gain insight into virulence mechanism. As the infections are increasing rapidly, more divergence is expected followed possibly by viral adaptation. We could identify mutational hotspots which appear to be major drivers of diversity among strains, with RBD of spike protein emerging as the key region involved in interaction with ACE2 and consequently a major determinant of infection outcome. We believe that such molecular analyses correlated with clinical characteristics and host predisposition need to be evaluated at the earliest to understand viral adaptability, disease prognosis, and transmission dynamics.

Keywords: COVID-19; Coronavirus; Molecular divergence; Phylogenetics; SARS-CoV-2.

Fig. 1

Visual depiction of emerging genomic diversity among clinical isolates of SARS-CoV-2 (A) SARS-CoV-2 separating into different clades since its identification in December 2019 till March 2020 using Wuhan-Hu-1/2019 (NC_045512) as reference strain (courtesy: nextstrain.org). Amino acid mutations in individual ORF’s are also shown that lead to clade separation. (B) t-distributed stochastic neighbour embedding (tSNE), a non-linear dimensionality reduction Machine learning (ML) technique plot for COVID-19 strains (n=257, based on the global ORF similarity between genomes) highlights two dominant clusters; Europe and North America + Asia). Diffuse geographical clustering was observed for other strains across continents - an indication of the effects of human migration in the modern population. (C) Mutation analysis of all ORF’s from analysed COVID-19 strains (n=257). Plots for individual amino acids in ORF’s show that every type of amino acid has undergone mutations, predominantly in ORF’s 1ab, S, 3a and E. (D) Diversity in clinical isolates indicate that SARS-CoV-2 has divulged into at least five different clades, evolutionary distinct from Bat CoV RaTG13 and Beta-CoV-pangolins.