Using iCn3D and the World Wide Web for structure-based collaborative research: Analyzing molecular interactions at the root of COVID-19

The COVID-19 pandemic took us ill-prepared and tackling the many challenges it poses in a timely manner requires world-wide collaboration. Our ability to study the SARS-COV-2 virus and its interactions with its human host in molecular terms efficiently and collaboratively becomes indispensable and mission-critical in the race to develop vaccines, drugs, and neutralizing antibodies. There is already a significant corpus of 3D structures related to SARS and MERS coronaviruses, and the rapid generation of new structures demands the use of efficient tools to expedite the sharing of structural analyses and molecular designs and convey them in their native 3D context in sync with sequence data and annotations. We developed iCn3D (pronounced “I see in 3D”) 1 to take full advantage of web technologies and allow scientists of different backgrounds to perform and share sequence-structure analyses over the Internet and engage in collaborations through a simple mechanism of exchanging “lifelong” web links (URLs). This approach solves the very old problem of “sharing of molecular scenes” in a reliable and convenient manner. iCn3D links are sharable over the Internet and make data and entire analyses findable, accessible, and reproducible, with various levels of interoperability. Links and underlying data are FAIR 2 and can be embedded in preprints and papers, bringing a 3D live and interactive dimension to a world of text and static images used in current publications, eliminating at the same time the need for arcane supplemental materials. This paper exemplifies iCn3D capabilities in visualization, analysis, and sharing of COVID-19 related structures, sequence variability, and molecular interactions.

[1]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[2]  Lewis Y. Geer,et al.  Cn3D: sequence and structure views for Entrez. , 2000, Trends in biochemical sciences.

[3]  Cathy H. Wu,et al.  UniProt: the Universal Protein knowledgebase , 2004, Nucleic Acids Res..

[4]  Mathieu Rouard,et al.  IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. , 2005, Developmental and comparative immunology.

[5]  Chengsheng Zhang,et al.  Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 , 2005, The EMBO journal.

[6]  S. Harrison,et al.  Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor , 2005, Science.

[7]  Yang Feng,et al.  Structure of Severe Acute Respiratory Syndrome Coronavirus Receptor-binding Domain Complexed with Neutralizing Antibody* , 2006, Journal of Biological Chemistry.

[8]  Fang Li,et al.  Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections , 2008, Journal of Virology.

[9]  Fang Li,et al.  Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor , 2009, Proceedings of the National Academy of Sciences.

[10]  Michael Habeck,et al.  The GD box: A widespread noncontiguous supersecondary structural element , 2009, Protein science : a publication of the Protein Society.

[11]  Yanli Wang,et al.  MMDB: 3D structures and macromolecular interactions , 2011, Nucleic Acids Res..

[12]  Yi Shi,et al.  Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26 , 2013, Nature.

[13]  Dachuan Zhang,et al.  MMDB and VAST+: tracking structural similarities between macromolecular complexes , 2013, Nucleic Acids Res..

[14]  Narmada Thanki,et al.  CDD: NCBI's conserved domain database , 2014, Nucleic Acids Res..

[15]  Wen J. Li,et al.  Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation , 2015, Nucleic Acids Res..

[16]  Cathy H. Wu,et al.  UniProt: the universal protein knowledgebase , 2016, Nucleic Acids Research.

[17]  F. Dimaio,et al.  Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer , 2016, Nature.

[18]  Barney S. Graham,et al.  Pre-fusion structure of a human coronavirus spike protein , 2016, Nature.

[19]  Meitian Wang,et al.  Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1 , 2017, Nature Communications.

[20]  F. Arnaud,et al.  From core referencing to data re-use: two French national initiatives to reinforce paleodata stewardship (National Cyber Core Repository and LTER France Retro-Observatory) , 2017 .

[21]  Philippe Youkharibache.  Twelve Elements of Visualization and Analysis for Tertiary and Quaternary Structure of Biological Molecules , 2017 .

[22]  Xinquan Wang,et al.  Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 , 2018, PLoS pathogens.

[23]  John L Rubinstein,et al.  The human coronavirus HCoV-229E S-protein structure and receptor binding , 2019, eLife.

[24]  Masashi Yokochi,et al.  Announcing mandatory submission of PDBx/mmCIF format files for crystallographic depositions to the Protein Data Bank (PDB). , 2019, Acta crystallographica. Section D, Structural biology.

[25]  Alexandra C Walls,et al.  Structural basis for human coronavirus attachment to sialic acid receptors , 2019, Nature Structural & Molecular Biology.

[26]  K. Yuen,et al.  Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 , 2020, Cell.

[27]  Philippe Youkharibache,et al.  Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins , 2020, Journal of Molecular Evolution.

[28]  John R. Mascola,et al.  A strategic approach to COVID-19 vaccine R&D , 2020, Science.

[29]  Qiang Zhou,et al.  Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 , 2020, Science.

[30]  L. Guddat,et al.  Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase , 2020, Cell.

[31]  Yang Yang,et al.  A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 , 2020, Science.

[32]  Shibo Jiang,et al.  Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine , 2020, Cellular & Molecular Immunology.

[33]  Megan Scudellari.  The sprint to solve coronavirus protein structures — and disarm them with drugs , 2020, Nature.

[34]  B. Graham,et al.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation , 2020, Science.

[35]  Linqi Zhang,et al.  Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor , 2020, Nature.

[36]  K. Shi,et al.  Structural basis of receptor recognition by SARS-CoV-2 , 2020, Nature.

[37]  Jiyao Wang,et al.  iCn3D, a web-based 3D viewer for sharing 1D/2D/3D representations of biomolecular structures , 2019, Bioinform..

[38]  E. Holmes,et al.  The proximal origin of SARS-CoV-2 , 2020, Nature Medicine.

[39]  Barney S. Graham,et al.  Rapid COVID-19 vaccine development , 2020, Science.