Structure of Furin Protease Binding to SARS-CoV‑2 Spike Glycoprotein and Implications for Potential Targets and Virulence

The
COVID-19 pandemic is an urgent global health emergency, and
the presence of Furin site in the SARS-CoV-2 spike glycoprotein alters
virulence and warrants further molecular, structural, and biophysical
studies. Here we report the structure of Furin in complex with SARS-CoV-2
spike glycoprotein, demonstrating how Furin binds to the S1/S2 region
of spike glycoprotein and eventually cleaves the viral protein using
experimental functional studies, molecular dynamics, and docking.
The structural studies underline the mechanism and mode of action
of Furin, which is a key process in host cell entry and a hallmark
of enhanced virulence. Our whole-exome sequencing analysis shows the
genetic variants/alleles in Furin were found to alter the binding
affinity for viral spike glycoprotein and could vary in infectivity
in humans. Unravelling the mechanisms of Furin action, binding dynamics,
and the genetic variants opens the growing arena of bona fide antibodies
and development of potential therapeutics targeting the blockage of
Furin cleavage.