J. Rausch, A. Capoferri, M. G. Katusiime, S. Patro, M. Kearney
Proceedings of the National Academy of Sciences, 2020
Scientists worldwide are racing to develop effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic. An important and perhaps underappreciated aspect of this endeavor is ensuring that the vaccines being developed confer immunity to all viral lineages in the global population. Toward this end, a seminal study published in PNAS (1) analyzes 27,977 SARS-CoV-2 sequences from 84 countries obtained throughout the course of the pandemic to track and characterize the evolution of the novel coronavirus since its origination. The principle conclusion reached by the authors of this work is that SARS-CoV-2 genetic diversity is remarkably low, almost entirely the product of genetic drift, and should not be expected to impede development of a broadly protective vaccine. Although errors introduced during genome replication are a major source of genetic variation in all virus populations, limiting the fitness costs of accumulated errors is especially critical for coronaviruses, the RNA genomes of which are the largest known. For this reason, coronaviruses evolved nonstructural protein 14 (nsp14), which accompanies viral replicases during RNA synthesis and excises misincorporated ribonucleotides from nascent strands before they can be extended, thus preventing errors from becoming permanent. This error-correcting capacity was unknown among RNA viruses prior to its discovery in SARS-CoV-1 (2, 3), and it contributes to a replication error rate more than 10-fold lower than that of other RNA viruses (4, 5). This activity also likely contributes to the low genetic diversity of SARS-CoV-2, although to our knowledge nsp14 function in the novel coronavirus has yet to be investigated. For many viruses, surface glycoproteins contain not only elements required for specific binding of cellular receptors, membrane fusion, and virus entry into the host cell but also epitopes recognized by neutralizing antibodies produced as part of an effective adaptive … [↵][1]1To whom correspondence may be addressed. Email: kearneym{at}mail.nih.gov. [1]: #xref-corresp-1-1
Cited by 30 publications.
Field of study: Biology