Receptor binding domain of SARS CoV2 spike protein exhibits in vitro liquid-liquid phase separation due to structural disorderedness that may challenge the vaccine-generated antibody binding.

In this study we expressed, purified and demonstrated the protein liquid-liquid phase separation (LLPS) formation by the receptor binding domain (RBD) of coronavirus spike protein in vitro. Our molecular dynamics simulations revealed multiple structurally disordered regions lacking secondary structural elements within RBD that exhibited high structural flexibility with deviations as high as 6 Å over 500 ns in support of our in vitro findings. Additionally these disordered regions overlap with epitopes potentially altering their architecture. Based on these results we conclude that the structural disorderedness of RBD causes LLPS formation in vitro and may potentially challenge the COVID-19 vaccine efficacy.