Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2

TLDR

The authors developed a real‑time mutation‑tracking pipeline for SARS‑CoV‑2, focusing on the Spike protein to monitor changes that may affect infection and vaccine targets. The pipeline analyzes Spike mutations in a phylogenetic, geographic, and temporal framework, applying positive‑selection tests and structural modeling to flag variants that could enhance transmission or evade interventions. The study identified thirteen accumulating Spike mutations, highlighted the rapidly spreading D614G variant that quickly dominates new regions, found evidence of recombination among local strains, and underscored the implications for transmission, pathogenesis, and immune interventions.

Abstract

Summary We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.