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COVID-19 math: gene content, mutations, and clinical trial analysis:
We will explore three areas where a quantitative approach is helpful in understanding SARS-CoV-2 and combating the COVID-19 pandemic. First, we use tools that quantify evolutionary signatures of protein-coding genomic regions to determine the conserved gene content of SARS-CoV-2, which, surprisingly, was previously unresolved. Using 44 complete Sarbecovirus genomes at evolutionary distances ideally-suited for protein-coding and non-coding element identification, we find strong protein-coding signatures for all named genes and for 3a, 6, 7a, 7b, 8, 9b, and also ORF3c, a novel alternate-frame gene. By contrast, ORF10 and overlapping-ORFs 9c lack protein-coding signatures. Furthermore, we show no other conserved protein-coding genes remain to be discovered. Second, we use our Sarbecovirus alignments to prioritize functional mutations from the ongoing COVID-19 pandemic. Cross-strain and within-strain evolutionary pressures largely agree at the gene, amino-acid, and nucleotide levels, with some notable exceptions, including fewer-than-expected mutations in nsp3 and Spike subunit S1, and more-than-expected mutations in Nucleocapsid. The latter also shows a cluster of amino-acid-changing variants in otherwise-conserved residues in a predicted B-cell epitope, which may indicate positive selection for immune avoidance. Several Spike-protein mutations, including D614G, which has been associated with increased transmission, disrupt otherwise-perfectly-conserved amino acids, and could be novel adaptations to human hosts. Finally, we re-analyze the results of a clinical trial that found that calcifediol, a form of vitamin D, dramatically reduced the need for ICU care in hospitalized COVID-19 patients.

Jan 14, 2021 07:00 PM in Eastern Time (US and Canada)

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