?:abstract
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The genome of SARS-CoV-2, the coronavirus responsible for the Covid-19 pandemic, encodes a number of accessory genes The longest accessory gene, Orf3a, plays important roles in the virus lifecycle indicated by experimental findings, known polymorphisms, its evolutionary trajectory and a distinct three-dimensional fold Here we show that supervised, sensitive database searches with Orf3a detect weak, yet significant and highly specific similarities to the M proteins of coronaviruses The similarity profiles can be used to derive low-resolution three-dimensional models for M proteins based on Orf3a as a structural template The models also explain the emergence of Orf3a from M proteins and suggest a recent origin across the coronavirus lineage, enunciated by its restricted phylogenetic distribution This study provides evidence for the common origin of M and Orf3a families and proposes for the first time a working model for the structure of the universally distributed M proteins in coronaviruses, consistent with the properties of both protein families
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