Objectives: SARS-CoV-2 spike (S) glycoprotein furin cleavage site is a key determinant of SARS-CoV-2 virulence and COVID-19 pathogencity. Located at the S1/S2 junction, it is unique among sarbecoviruses but frequently found among betacoronaviruses. Recent evidence suggests that this site includes two additional functional motifs: a pat7 nuclear localization signal and two flanking O-glycosites. However, a systematic genus and subgenus analysis of spike protein sequences bearing this polyfunctional sequence domain has been missing.

Data Description: Here we report comprehensive sequence data to demonstrate that among spike proteins of genus Betacoronavirus and outside of the SARS-CoV-2 clade a fully analogous S1/S2 domain was found in only one other virus: the artificial MERS infectious clone MERS-MA30, described already in 2017, which was rationally selected from serial passage in genetically humanized mice. As the evolutionarily closest betacoronaviruses outside of the SARS-CoV-2 clade lack all its three functional motifs, these data extend-beyond natural evolution and zoonosis-the current view on SARS-CoV-2 pre-pandemic origins by presenting the analogous S1/S2 MERS-MA30 sequence domain as a precise molecular blueprint for SARS-CoV-2.

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http://dx.doi.org/10.1186/s12863-024-01290-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650820PMC

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