The Mutation Profile of SARS-CoV-2 Is Primarily Shaped by the Host Antiviral Defense.

Cem Azgari,Berk Turhan,Ogun Adebali,Defne Circi,Zeynep Kilinc

doi:10.3390/v13030394

Abstract

Understanding SARS-CoV-2 evolution is a fundamental effort in coping with the COVID-19 pandemic. The virus genomes have been broadly evolving due to the high number of infected hosts world-wide. Mutagenesis and selection are two inter-dependent mechanisms of virus diversification. However, which mechanisms contribute to the mutation profiles of SARS-CoV-2 remain under-explored. Here, we delineate the contribution of mutagenesis and selection to the genome diversity of SARS-CoV-2 isolates. We generated a comprehensive phylogenetic tree with representative genomes. Instead of counting mutations relative to the reference genome, we identified each mutation event at the nodes of the phylogenetic tree. With this approach, we obtained the mutation events that are independent of each other and generated the mutation profile of SARS-CoV-2 genomes. The results suggest that the heterogeneous mutation patterns are mainly reflections of host (i) antiviral mechanisms that are achieved through APOBEC, ADAR, and ZAP proteins, and (ii) probable adaptation against reactive oxygen species.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide since its emergence in December 2019 [1], reportedly infecting more than 83 million people, with a death toll of 2,455,131 as of 22 February 2021, according to World Health Organization (WHO)
3 out of the 5 most frequently changed trinucleotides contain CG at their second and third positions. To examine whether these mutations were predominantly located at a single position in the viral genome or are distributed throughout the genome, we identified dynamic positions, where more than 8 recurring mutations were observed
Afterwards, we investigated the contribution of these trinucleotide positions to the mutation profile (Figure 2B,C)

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide since its emergence in December 2019 [1], reportedly infecting more than 83 million people, with a death toll of 2,455,131 as of 22 February 2021, according to World Health Organization (WHO) (https://covid19.who.int/). Studies have been focused on effective treatment of the disease, mostly by the drug re-purposing approach due to the urgency [2] and by finding a vaccine that will stop the spread of the virus. Though there are dozens of vaccine candidates in clinical development, the evolutionary potential of the virus might affect the efficacy of the immunizations and treatments. Understanding the genomic features and mutation dynamics of the virus is crucial to interpret its evolutionary patterns and its response to the available treatments and potential vaccines. Analyzing virus sequence context and mutations has revealed essential characteristics of SARS-CoV-2. We and others studied the spread of the virus in a variety of countries by tracking the mutation events of sequences over time [8,9,10]

Methods

Results

Conclusion