SARS-CoV-2 Worldwide Replication Drives Rapid Rise and Selection of Mutations across the Viral Genome: A Time-Course Study Potential Challenge for Vaccines and Therapies (preprint)

ABSTRACT

Scientists and the public were alarmed at the first large viral variant of SARS-CoV2 reported in December 2020. We have followed the time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries on four continents. We examined complete SARS-CoV-2 nucleotide sequences in GISAID, (Global Initiative of Sharing All Influenza Data) with sampling dates extending until January 20, 2021. These sequences originated from ten different countries United Kingdom, South Africa, Brazil, USA, India, Russia, France, Spain, Germany, and China. Among the novel mutations, some previously reported mutations waned and some of them increased in prevalence over time. VUI2012/01 (B.1.1.7) and 501Y.V2 (B.1.351), the so-called UK and South Africa variants, respectively, and two variants from Brazil, 484K.V2, now called P.1 and P.2, increased in prevalence. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations. The data on mutant and variant SARS-CoV-2 strains provided here comprise a global resource for easy access to the myriad mutations and variants detected to date globally. Rapidly evolving new variant and mutant strains might give rise to escape variants, capable of limiting the efficacy of vaccines, therapies, and diagnostic tests. Significance and New Aspects of Study – Synopsis We examine the time course of emerging mutations in the SARS-CoV-2 genome that have rapidly been selected in the world’s populations through the beginning of 2021. A study of the prevalence of viral mutations in the GISAID database in ten different countries – United Kingdom, South Africa, Brazil, US, India, Russia, France, Spain, Germany, and China - revealed widespread mutations along the genome. We previously identified about 10 hotspot mutations in the SARS-CoV-2 genome that became prevalent in many of the countries studied 1 . Since the beginning of February, many new mutations arose in the ten countries (and worldwide). The preponderance of variants and mutations correlated with the increased spread of Covid-19. There was a temporal progression from about 10 predominant mutants shared by several countries up to the end of May 2020, followed by a consistent and rapid increase in the number of new mutations between June and December along with the emergence of variants of concern, first reported in December 2020. We examine the relative frequencies of mutations, along with variants of interest, in 10 countries up until January 20, 2021. Investigations on the pathogenic properties of individual SARS-CoV-2 mutations will be urgently needed to understand the kaleidoscopic patterns of worldwide Covid-19 outbreaks and symptoms. Monitoring the frequency and speed of mutant selection have direct relevance to diagnostic testing, vaccines and therapeutics. As an explanation for efficient viral mutagenesis, we hypothesize that the viral spike protein – as documented – facilitates viral entry via the cell’s ACE receptor 2 . This in turn interacts with the APOBEC polypeptide, an m-RNA editing function. The actually observed frequent C to U (T) transitions and other base exchanges are thus effected. Hence, as one of the earliest steps upon viral entry, active mutagenesis commences, since SARS-CoV-2 exploits one of the cell’s defenses against viral infections.