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 domain is present in the attenuated rubella virus used in the MMR vaccine. Although it is within a cytoplasmic non-structural protein, it could contribute to vaccine antigenicity if it released upon cell lysis, or displayed via MHC-I in vaccinated patients. Hence, we hypothesise that potentially immunogenic elements of the SARS-CoV-2 Macro domain that are conserved in rubella virus could serve as targets for B-or T-cell responses in patients who have had rubella or received a version of the vaccine. In this regard, we note certain antibodies raised against the S surface glycoprotein of SARS-CoV cross-neutralize SARS-CoV-2 [Wang et al., 2020; Lv et al., 2020; Walls et al., 2020] , but it remains unclear to what extent non-neutralizing antibody cross-reactivity may lead to antibody-dependent enhancement [Lv et al., 2020] . Viral envelope glycoproteins catalyse an essential step in cell entry, fusion of the viral and cellular membrane. Coronavirus Spike glycoproteins are class I viral membrane fusion proteins. As such they share the same trimeric a-helical coiled-coil architecture as other class I fusogens including those from ortho-and paramyxoviruses [Walls et al., 2017; Skehel et al., 2000] . Structural homology searches with DALI [Holm et al., 2016] and molecular modelling with PHYRE2 [Kelley et al., 2015] confirmed clear structural homology between the SARS-CoV-2 Spike and paramyxovirus F proteins, including both measles and measles F in the postfusion conformation (DALI Z-score 6.3; Fig. 2 ). Homologous sequences in SARS-CoV-2 S2 and measles, aligned in PSI-BLAST [Altschul et al., 1997] with an expected value of 10 -101 , with 20% sequence identity over a 369-amino acid region (Fig. 3 ). An extensive set of surface-exposed residues is conserved in SARS-CoV-2 S2 and measles F. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.