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In this manuscript we describe the investigation of the SARS-CoV2 membranefusion timescale by means of small-angle neutron scattering (SANS) usinghydrogen/deuterium contrast variation. After the successful production ofvirus-like vesicles and human-host-cell-like vesicles we were able to followthe fusion of the respective vesicles in real-time. This was done usingdeuterated and protonated phospholipids in the vesicles in a neutron-contrastmatched solvent. The vesicles were identical apart from either the presence orabsence of the SARS-CoV2 spike protein. The human-host-cell-like vesicles werecarrying an ACE2 receptor protein in all cases. In case of the absence of thespike protein a fusion over several hours was observed in agreement withliterature, with a time constant of 4.5 h. In comparison, there was nottime-evolution, but immediate fusion of the vesicles when the spike protein waspresent. Those two figures, fusion over several hours and fusion below 10 scorresponding to the absence or presence of the spike protein allow anupper-limit estimate for the fusion times of virus-like vesicles with theSARS-CoV2 spike protein of 10 s. This very fast fusion, when compared to thecase without spike protein it is a factor of 2500, can also help to explain whyinfection with SARS-CoV2 can be so effective and fast. Studying spike proteinvariants using our method may explain differences in transmissibility betweenSARS-CoV2 strains. In addition, the model developed here can potentially beapplied to any enveloped virus.

Timescales of Cell Membrane Fusion Mediated by SARS-CoV2 Spike Protein and its Receptor ACE2