CoV3D: a database of high resolution coronavirus protein structures.

Ragul Gowthaman,Brian G Pierce,Jared Adolf-Bryfogle,William R Schief,Johnathan D Guest,Rui Yin

doi:10.1093/nar/gkaa731

Abstract

SARS-CoV-2, the etiologic agent of COVID-19, exemplifies the general threat to global health posed by coronaviruses. The urgent need for effective vaccines and therapies is leading to a rapid rise in the number of high resolution structures of SARS-CoV-2 proteins that collectively reveal a map of virus vulnerabilities. To assist structure-based design of vaccines and therapeutics against SARS-CoV-2 and other coronaviruses, we have developed CoV3D, a database and resource for coronavirus protein structures, which is updated on a weekly basis. CoV3D provides users with comprehensive sets of structures of coronavirus proteins and their complexes with antibodies, receptors, and small molecules. Integrated molecular viewers allow users to visualize structures of the spike glycoprotein, which is the major target of neutralizing antibodies and vaccine design efforts, as well as sets of spike-antibody complexes, spike sequence variability, and known polymorphisms. In order to aid structure-based design and analysis of the spike glycoprotein, CoV3D permits visualization and download of spike structures with modeled N-glycosylation at known glycan sites, and contains structure-based classification of spike conformations, generated by unsupervised clustering. CoV3D can serve the research community as a centralized reference and resource for spike and other coronavirus protein structures, and is available at: https://cov3d.ibbr.umd.edu.

Highlights

Coronaviruses (CoVs) have been responsible for several outbreaks over the past two decades, including SARS-CoV in 2002-2003, MERS-CoV in 2012 [1], and the current COVID-19 pandemic, caused by SARS-CoV-2, which began in late 2019 [2]
Database contents The main components of the CoV3D database are interrelated tables, datasets, and tools for coronavirus protein structures and spike glycoprotein sequences
Peptide-Major Histocompatibility Complex (MHC) structures with coronavirus peptides Spike glycoprotein structures are annotated by binding partner(s), including bound antibody and receptor, as well as domains present in the structure

Summary

Introduction

Coronaviruses (CoVs) have been responsible for several outbreaks over the past two decades, including SARS-CoV in 2002-2003, MERS-CoV in 2012 [1], and the current COVID-19 pandemic, caused by SARS-CoV-2, which began in late 2019 [2]. As of June 17th, 2020, this includes 28 spike glycoprotein structures, over 150 main protease structures, and over 60 structures of other SARS-CoV-2 proteins. These high-resolution protein structures are of immense importance for understanding viral assembly and to aid rational vaccine and therapeutic design. The first structures of the SARS-CoV-2 trimeric spike glycoproteins (the major target of SARS-CoV-2 vaccines and antibody therapeutics) were reported in February and early March 2020 [4,5]. Determined spike glycoprotein structures have enabled advances including rational stability optimization of SARS-CoV and MERS-CoV spikes, yielding improved protein expression and immunogenicity [6]. Given that the rapid rate of coronavirus protein structural determination and deposition is likely to continue, a simple and updated resource detailing these structures would provide a useful reference

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