A New Crystal Form of the SARS-CoV-2 Receptor Binding Domain: CR3022 Complex-An Ideal Target for In-Crystal Fragment Screening of the ACE2 Binding Site Surface.

Charlie Nichols,Annika Keshu,Joseph Ng,Gian F De Nicola,Franca Fraternali

doi:10.3389/fphar.2020.615211

Charlie Nichols, Annika Keshu + Show 3 more

Open Access

https://doi.org/10.3389/fphar.2020.615211

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Abstract

In-crystal fragment screening is a powerful tool to chemically probe the surfaces used by proteins to interact, and identify the chemical space worth exploring to design protein-protein inhibitors. A crucial prerequisite is the identification of a crystal form where the target area is exposed and accessible to be probed by fragments. Here we report a crystal form of the SARS-CoV-2 Receptor Binding Domain in complex with the CR3022 antibody where the ACE2 binding site on the Receptor Binding Domain is exposed and accessible. This crystal form of the complex is a valuable tool to develop antiviral molecules that could act by blocking the virus entry in cells.

Highlights

A new form of viral pneumonia caused by the coronavirus named SARS-CoV-2 was first reported in Wuhan China at the end of 2019 and has since been declared a pandemic by the World Health Organization
In the crystal form we present here (PDB 6ZLR), the resolution of the complex is 3.1 (Table 1) in chain E the entire ACE2 binding site on the Receptor Binding Domain (RBD) is free from lattice contacts and accessible to solvent, making such form an ideal target for chemical exploration with fragments of that surface (Yuan et al, 2020; Huo et al, 2020)
The SARS-CoV-2-RBD and CR3022 proteins were provided by Prof Ian Wilson, both in 150 mM NaCl and 20 mM Tris pH 7.5

Summary

A New Crystal Form of the SARS-CoV-2 Receptor Binding Domain

Charlie Nichols 1,2, Joseph Ng 1, Annika Keshu 1, Franca Fraternali 1 and Gian F. Complex—An Ideal Target for InCrystal Fragment Screening of the ACE2 Binding Site Surface. A crucial prerequisite is the identification of a crystal form where the target area is exposed and accessible to be probed by fragments. We report a crystal form of the SARS-CoV-2 Receptor Binding Domain in complex with the CR3022 antibody where the ACE2 binding site on the Receptor Binding Domain is exposed and accessible. This crystal form of the complex is a valuable tool to develop antiviral molecules that could act by blocking the virus entry in cells

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