2024/02/28 by Zach Hensel · 1 voice · 1 citation
Agricultural and Biological Sciences · Medicine · #Animal Virus Infections Studies #SARS-CoV-2 and COVID-19 Research #Viral gastroenteritis research and epidemiology
paper · pdf · doi:10.1101/2024.02.27.581995
openalex publication_date 2024/02/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14
Abstract Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern (Carabelli et al ., 2023). Recently, Lan et al . reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate (DMS) reactivity data (Lan et al ., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated “mutational fitness” of substitutions, a measurement of the difference between a substitution’s observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.