Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by SNR, SANS, QENS, and NSE experiments

Due to the COVID-19 pandemic, a thorough understanding of the molecular mechanisms of cellular infection by coronaviruses has become imperative. SARS-CoV-2 is from a family of single-stranded positive sense RNA viruses named β-coronaviruses. SARS-CoV-2 and other β-coronaviruses can cause severe respiratory dis-ease and are highly contagious. Despite this, a critical understanding of the mechanisms of cellular infection by coronaviruses has been lacking. A critical stage in cell entry by the SARS-CoV-2 virus occurs when its Spike protein mediates fusion between viral and host membranes (Figure 1). We have therefore recreated important elements of the membrane fusion mechanism by simpli-fying the system down to its core elements, amenable to experimental analysis by neutron scattering at the ILL. Structural information from Specular Neutron Reflectometry and Small Angle Neutron Scattering were com-plemented by dynamics information from Quasi-Elastic and Spin-Echo neutron scattering, accessing membrane fluidity and rigidity. Importantly, neutrons are particu-larly well suited for the study of soft and biological matter since they allow measurements with better than nanometer resolution and at energies corresponding to thermal fluctuations. They are non-destructive and highly penetrating, thus allowing work in physiological condi-tions. Furthermore, as neutrons interact very differently with hydrogen ( 1 H) and deuterium ( 2 H), it is possible through isotopic substitution, to observe hydrogen atoms and water molecules in biological samples, and therefore highlight structural and chemical differences in