Crystal Structure Determination and Receptor Recognition Basis of SARS-CoV-2 Spike Glycoprotein

A new coronavirus outbreak has emerged in Wuhan, China, in 2019 and turned into a global pandemic posing a massive public health concern. Its genome has been sequenced and showed pairwise percent identities of approximately 79.5% and 50% compared to severe acute respiratory syndrome-coronavirus (SARS-CoV) and the Middle East respiratory syndrome-coronavirus (MERS-CoV), respectively. The coronavirus spike glycoprotein is the primary determinant of viral tropism and is responsible for receptor binding and membrane fusion. The receptor-binding domain of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been characterized and structurally identified through X-ray crystallography and cryoelectron microscopy. The variations in residual sequences, hidden receptor binding domain, and furin-like cleavage nature of the spike clarified the higher receptor affinity and efficient spread among humans compared to SARS-CoV. The spike glycoprotein is a vital target for vaccines and therapeutic antibodies. Correspondingly, the potential implication of its structure elucidation in developing new and cross-neutralizing antibodies targeting the spike epitopes has been briefly discussed. Here, it is expected that the elaborated details of the molecular structure may facilitate the opportunity of developing therapeutics against SARS-CoV-2.

Keywords: COVID19, Crystal structure, Neutralizing antibody, Receptor binding domain, SARS-CoV-2, Spike glycoprotein, Vaccine.