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

Dominic Hayward; Purushottam S Dubey; Marie-Sousai Appavou; Olaf Holderer; Henrich Frielinghaus; Sylvain Prevost; Bela Farago; Anna Sokolova; Piotr Zolnierczuk; Heiner von Buttlar; Peter Braun; Joachim Jakob Bugert; Rosina Ehmann; Sebastian Jaksch

arXiv · 2303.10746

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

Dominic Hayward·Purushottam S Dubey·Marie-Sousai Appavou·Olaf Holderer·Henrich Frielinghaus·Sylvain Prevost·Bela Farago·Anna Sokolova·Piotr Zolnierczuk·Heiner von Buttlar·Peter Braun·Joachim Jakob Bugert·Rosina Ehmann·Sebastian Jaksch

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Abstract

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.

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Dominic Hayward, Purushottam S Dubey, Marie-Sousai Appavou, Olaf Holderer, Henrich Frielinghaus, Sylvain Prevost, Bela Farago, Anna Sokolova, Piotr Zolnierczuk, Heiner von Buttlar, Peter Braun, Joachim Jakob Bugert, Rosina Ehmann, Sebastian Jaksch. 2023-03-19. Timescales of Cell Membrane Fusion Mediated by SARS-CoV2 Spike Protein and its Receptor ACE2. https://arxiv.org/abs/2303.10746

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