WHO SAGO 18 February 2025 meeting presentation of data supporting non-natural origin hypothesis of SARS-CoV-2 spike protein furin cleavage site

Data Assembly and Presentation Material: Dr. Andreas Martin Lisewski (CUB)
Data Presenter at WHO SAGO Meeting: Prof. Dr. Christian Drosten (WHO SAGO)

World Health Organization (WHO) Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) 18 February 2025 meeting presentation of data supporting non-natural SARS-CoV-2 origin hypothesis. Supplementary observational data (indicated or referenced  with *) was not directly presented during this meeting. Presented and supplementary data result in hypothesis that SARS-CoV-2 S1/S2 furin cleavage site (FCS) was rationally inserted into a RaTG13(-like), propagated backbone with recombinant gain-of-function (GoF) MERS-MA30/MA1.0 CoV spike FCS serving as precise molecular blueprint (design target) at the amino acid level. At nucleotide level, two combined type IIS restriction enzyme recognition sites (FauI and MnlI) essentially encode the MERS-MA30/MA1.0 FCS target as seen in SARS-CoV-2, to which ancestral (15 December 2019) D614G lineage evolved through spike reversal mutations prior to the onset of the pandemic. Parental recombinant MERS-MA30 CoV and MERS-MA1.0 CoV clones were the result of GoF research, published by 2017, through directed MERS CoV serial passaging, adaptation and rational selection in human entry receptor knockin (humanized) laboratory mice (murine adapted, MA30), as well as through FCS targeted reverse genetics engineering (MA1.0), respectively. WHO SAGO report on SARS-CoV-2 origins with announced reference to these data is yet to be published (as of 5/2025).