Prefusion conformation of SARS-CoV-2 receptor-binding domain favours interactions with human receptor ACE2

A new coronavirus epidemic COVID-19 caused by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) poses serious threat across continents, leading to the World Health Organization declaration of a Public Health Emergence of International Concern. In order to stop the entry of the virus into human host cell, major therapeutic and vaccine design efforts are now targeting interactions between the SARS-CoV-2 spike (S) glycoprotein and the human cellular membrane receptor angiotensin-converting enzyme, hACE2. By analysing cryo-EM structures of SARS-CoV-2 and SARS-CoV-1, we report here that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) that bind with hACE2 has expanded in size with a large conformational change of its AA residues relative to SARS-CoV-1 S protein. Protomer with the up-conformational form RBD that only can bind with hACE2 showed higher intermolecular interactions at the interface, with differential distributions and the inclusion of two specific H-bonds in the CoV-2 complex. However, these interactions are resulted in significant reductions in structural rigidity, favouring proteolytic processing of S protein for the fusion of the viral and cellular membrane. Further conformational dynamics analysis of the RBD motions of SARS-CoV-2 and SARS-CoV-1 point to the role in modification in the RBD conformational dynamics and their likely impact on infectivity.