Apr 12, 2020

Biophysical characterization of the SARS-CoV2 spike protein binding with the ACE2 receptor explains increased COVID-19 pathogenesis

BioRxiv : the Preprint Server for Biology
Constanza Maria PautassoSilvia Rossi


SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor angiotensin converting enzyme (ACE2). We contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domains (RBDs) from (i) SARS-CoV-2, (ii) the related but less virulent OC43 (Singapore COVID-19 strain), and (iii) the 2002 epidemic-causing SARS-CoV-1. We find that the RBDs of the spike protein of SARS-CoV-2 are highly optimized to achieve the strongest possible binding interaction with ACE2 which is consistent with its enhanced pathogenicity. SARS-CoV-2 RBDs form the most stable complex with ACE2 (64.91%, and 28.07% higher binding scores than SARS-CoV-1 and OC43, respectively) while occupying the greatest number of residues in the ATR1 binding site. In fact, the spike protein RBDs from SARS-CoV2 out-compete the angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 64% in terms of binding affinity (quantified using the Rosetta scoring function). They accomplish this through strong electrostatic attachments with every fourth residue on the N-terminus alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues...Continue Reading

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