  A recent experimental study found that the binding affinity between the
cellular receptor human angiotensin converting enzyme 2 (ACE2) and
receptor-binding domain (RBD) in spike (S) protein of novel severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) is more than 10-fold higher
than that of the original severe acute respiratory syndrome coronavirus
(SARS-CoV). However, main-chain structures of the SARS-CoV-2 RBD are almost the
same with that of the SARS-CoV RBD. Understanding physical mechanism
responsible for the outstanding affinity between the SARS-CoV-2 S and ACE2 is
the "urgent challenge" for developing blockers, vaccines and therapeutic
antibodies against the coronavirus disease 2019 (COVID-19) pandemic.
Considering the mechanisms of hydrophobic interaction, hydration shell, surface
tension, and the shielding effect of water molecules, this study reveals a
hydrophobic-interaction-based mechanism by means of which SARS-CoV-2 S and ACE2
bind together in an aqueous environment. The hydrophobic interaction between
the SARS-CoV-2 S and ACE2 protein is found to be significantly greater than
that between SARS-CoV S and ACE2. At the docking site, the hydrophobic portions
of the hydrophilic side chains of SARS-CoV-2 S are found to be involved in the
hydrophobic interaction between SARS-CoV-2 S and ACE2. We propose a method to
design live attenuated viruses by mutating several key amino acid residues of
the spike protein to decrease the hydrophobic surface areas at the docking
site. Mutation of a small amount of residues can greatly reduce the hydrophobic
binding of the coronavirus to the receptor, which may be significant reduce
infectivity and transmissibility of the virus.
