Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19

Robin Franklin; Adam Young; Bjoern Neumann; Rocio Fernandez; Alexis Joannides; Amir Reyahi; Yorgo Modis

The Macro domains of SARS-CoV-2 and rubella virus share 29% amino acid sequence identity, suggesting they have the same protein fold. We generated an atomic model of the rubella virus Macro domain by threading the rubella sequence onto the SARS-CoV-2 Macro structure, guided by secondary structure predictions, with PHYRE2 [Kelley et al., 2015] (100% confidence score; Fig. 1A ). Residues conserved in the SARS-CoV-2 and rubella Macro domains include surface-exposed residues and residues required for ADP-ribose binding and ADRP enzymatic activity in other coronaviruses ( Fig. 1) . Notably, ADRP activity is required for a mouse coronavirus, MHV-A59 (mouse hepatitis virus A59), to cause acute hepatitis. Mutation of a single residue in the MHV-A59 Macro domain (N1348A) abrogates ADRP activity [Eriksson et al., 2008] . This residue is conserved in the Macro domains of SARS-CoV-2 and rubella. Together these observations suggest that ADRP activity could be important in COVID-19 and rubella pathogenesis.