Structural dissection of viral spike‐protein binding of sars‐cov‐2 and sars‐cov‐1 to the human angiotensin‐converting enzyme 2 (Ace2) as cellular receptor

Abstract

An outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS‐CoV‐2) has spread CoronaVirus Disease 2019 (COVID‐19) all over the world. Immediately, following studies have confirmed the human Angiotensin‐Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike‐Protein (Sp) that mediates the CoV‐2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS‐CoV‐1 of 2002 and SARS‐ CoV‐2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp‐ACE2 complexes. The K417 amino acid residue, located in the region of Sp Receptor‐Binding Domain (RBD) of the new coronavirus SARS‐CoV‐2, showed to have a key role for the binding to the ACE2 N‐terminal region. The R426 residue of SARS‐CoV‐1 Sp‐RBD also plays a key role, alt-hough by interacting with the central region of the ACE2 sequence. Therefore, our study evidenced peculiarities in the interactions of the two Sp‐ACE2 complexes. Our outcomes were consistent with previously reported mutagenesis studies on SARS‐CoV‐1 and support the idea that a new and different RBD was acquired by SARS‐CoV‐2. These results have interesting implications and suggest further investigations.