Molecular Dynamics Reveals Complex Compensatory Effects of Ionic Strength on the Severe Acute Respiratory Syndrome Coronavirus 2 Spike/Human Angiotensin-Converting Enzyme 2 Interaction

The SARS-CoV-2 pandemic has already
killed more than one million
people worldwide. To gain entry, the virus uses its Spike protein
to bind to host hACE-2 receptors on the host cell surface and mediate
fusion between viral and cell membranes. As initial steps leading
to virus entry involve significant changes in protein conformation
as well as in the electrostatic environment in the vicinity of the
Spike/hACE-2 complex, we explored the sensitivity of the interaction
to changes in ionic strength through computational simulations and
surface plasmon resonance. We identified two regions in the receptor-binding
domain (RBD), E1 and E2, which interact differently with hACE-2. At
high salt concentration, E2-mediated interactions are weakened but
are compensated by strengthening E1-mediated hydrophobic interactions.
These results provide a detailed molecular understanding of Spike
RBD/hACE-2 complex formation and stability under a wide range of ionic
strengths.