bioRxiv preprint doi: https://doi.org/10.1101/2020.02.10.942136. this version posted February 14, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.
Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate
evolutionary conserved functional regions of viral proteins
Authors: Hongzhu Cui1,, Ziyang Gao1, Ming Liu1, Senbao Lu1, Sun Mo1, Winnie Mkandawire1, Oleksandr Narykov2, Suhas Srinivasan3, and Dmitry Korkin1,2,3,*
Affiliations
1Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA
01609
2Computer Science Department, Worcester Polytechnic Institute, Worcester, MA 01609
3Data Science Program, Worcester Polytechnic Institute, Worcester, MA 01609
*Corresponding author. E-mail: korkin@korkinlab.org
$The authors would like to note that the first eight authors are listed alphabetically.
Abstract
During its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of 2019-nCoV and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan
Figure 2. Structurally characterized non-structural proteins of 2019-nCoV. Highlighted in pink are mutations found when aligning the proteins against their homologs from the closest related coronaviruses: 2019-nCoV and human SARS, bat coronavirus, and another bat betacoronavirus BtRf-BetaCoV. The structurally resolved part of wNsp7 is sequentially identical to its homolog.
See Figure 2 in https://doi.org/10.1101/2020.02.10.942136
Figure 3. Structurally characterized structural proteins and an ORF of 2019-nCoV. Highlighted in pink are mutations found when aligning the proteins against their homologs from the closest related coronaviruses: 2019-nCoV and human SARS, bat coronavirus, and another bat betacoronavirus BtRf-BetaCoV. Highlighted in yellow are novel protein inserts found in wS.
See Figure 3 in https://doi.org/10.1101/2020.02.10.942136
Figure 4. Structurally characterized intra-viral and host-viral protein-protein interaction complexes of 2019-nCoV. Human proteins (colored in orange) are identified through their gene names. For each intra-viral structure, the number of subunits involved in the interaction is specified.
See Figure 4 in https://doi.org/10.1101/2020.02.10.942136
Figure 5. Evolutionary conservation of functional sites in 2019-nCoV proteins. A. Fully conserved protein binding sites (PBS, light orange) of wNsp12 in its interaction with wNsp7 and wNsp8 while other parts of the protein surface shows mutations (magenta); B. Both major monoclonal antibody binding site (light orange) and ACE2 receptor binding site (dark green) of wS are heavily mutated (binding site mutations are shown in red) compared to the same binding sites in other coronaviruses; mutations not located on the two binding sites are shown in magenta; C. Nearly intact protein binding site (light orange) of wNsp (papain-like protease PLpro domain) for its putative interaction with human ubiquitin-aldehyde (binding site mutations for the only two residues are shown in red, non-binding site mutations are shown in magenta); D. Fully conserved inhibitor ligand binding site (LBS, green) for wNsp5; non-binding site mutations are shown in magenta.
See Figure 5 in https://doi.org/10.1101/2020.02.10.942136
SOURCE
Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv