Do NSm virulence factors in the Bunyavirales viral order originate from Gn gene duplication?

One-third of the nine WHO shortlisted pathogens prioritized for research and development in public health emergencies belong to the Bunyavirales order. Several Bunyavirales species carry an NSm protein that acts as a virulence factor. We predicted the structures of these NSm protein and unexpectedly found that in two families, its cytosolic domain is inferred to have a similar fold to the cytosolic domain of the viral envelope-forming glycoprotein N (Gncyto) encoded on the same genome fragment. We show that although the sequence identity between the NSmcyto and Gncyto domains is low, the conservation of the two zinc finger-forming CCHC motifs explains the predicted structural conservation. Importantly, our predictions provide a first glimpse into the long unknown structure of NSm and its link to virulence. Also, these predictions suggest that NSm is the result of a gene duplication event in the Bunyavirales Nairoviridae and Peribunyaviridae families, and that such events may be common in the recent evolutionary history of RNA viruses.