Map of SARS-CoV-2 spike epitopes not shielded by glycans

The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.

Shifting borders, crossing boundaries: The case of combined central and peripheral demyelination

The case report by Puthenparampil et al. suggests that heterogeneity of demyelinating diseases may be more complex than expected. The authors describe a female patient starting with isolated but relapsing myelitis (in the absence of oligoclonal bands or anti-aquaporin 4 antibodies) and later experiencing the simultaneous occurrence of inflammatory demyelinating polyneuropathy and of a tumefactive hippocampal brain lesion responsive to immunotherapy. As testing for antibodies against established and novel auto-antigens including neurofascin-155 was negative, this case may be regarded as an example for the unfolding spectrum of combined central and peripheral demyelination (CCPD) syndromes with so far unknown immunological target(s).