  In this manuscript we describe the investigation of the SARS-CoV2 membrane
fusion timescale by means of small-angle neutron scattering (SANS) using
hydrogen/deuterium contrast variation. After the successful production of
virus-like vesicles and human-host-cell-like vesicles we were able to follow
the fusion of the respective vesicles in real-time. This was done using
deuterated and protonated phospholipids in the vesicles in a neutron-contrast
matched solvent. The vesicles were identical apart from either the presence or
absence of the SARS-CoV2 spike protein. The human-host-cell-like vesicles were
carrying an ACE2 receptor protein in all cases. In case of the absence of the
spike protein a fusion over several hours was observed in agreement with
literature, with a time constant of 4.5 h. In comparison, there was not
time-evolution, but immediate fusion of the vesicles when the spike protein was
present. Those two figures, fusion over several hours and fusion below 10 s
corresponding to the absence or presence of the spike protein allow an
upper-limit estimate for the fusion times of virus-like vesicles with the
SARS-CoV2 spike protein of 10 s. This very fast fusion, when compared to the
case without spike protein it is a factor of 2500, can also help to explain why
infection with SARS-CoV2 can be so effective and fast. Studying spike protein
variants using our method may explain differences in transmissibility between
SARS-CoV2 strains. In addition, the model developed here can potentially be
applied to any enveloped virus.
