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. 2020 Mar 25;12(4):360.
doi: 10.3390/v12040360.

Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins

Suhas Srinivasan  1 , Hongzhu Cui  2 , Ziyang Gao  2 , Ming Liu  2 , Senbao Lu  2 , Winnie Mkandawire  2 , Oleksandr Narykov  3 , Mo Sun  2 , Dmitry Korkin  1   2   3
Affiliations

Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins

Suhas Srinivasan et al. Viruses. .

Abstract

During its first two and a half months, the recently emerged 2019 novel coronavirus, SARS-CoV-2, has already infected over one-hundred thousand people worldwide and has taken more than four thousand 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 leveraged data about the related coronaviruses that is readily available in public databases and integrated these data into a single computational pipeline. As a result, we provide comprehensive structural genomics and interactomics roadmaps of SARS-CoV-2 and use this information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community.

Keywords: 2019 novel coronavirus; 2019-nCoV; COVID-19; SARS-CoV-2; interactome; protein-protein interactions; structural genomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structural genomics and interactomics road map. Shown are the individual proteins and protein complexes targeted for structural characterization together with PDB ID of their templates from the Protein Data Bank (PDB).
Figure 2
Figure 2
Structurally characterized non-structural proteins of SARS-CoV-2. Highlighted in pink are mutations found when aligning the proteins against their homologs from the closest related coronaviruses: human SARS-CoV, bat coronavirus BtCoV, and another bat betacoronavirus BtRf-BetaCoV. The structurally resolved part of wNsp7 shares 100% sequence identity to its homolog.
Figure 3
Figure 3
Structurally characterized intra-viral and host–viral protein–protein interaction complexes of SARS-CoV-2. 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.
Figure 4
Figure 4
Evolutionary conservation of functional sites in SARS-CoV-2 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 the major monoclonal antibody binding site (light orange) and the 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 of 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.
Figure 5
Figure 5
Structurally characterized structural proteins and an ORF of SARS-CoV-2. Highlighted in pink are mutations found when aligning the proteins against their homologs from the closest related coronaviruses: human SARS-CoV, bat coronavirus BtCoV, and another bat betacoronavirus BtRf-BetaCoV. Highlighted in yellow are novel protein inserts found in wS.
Figure 6
Figure 6
The unified interactome with SARS-CoV-2 interactions inferred through homology. (A) The SARS-CoV intra-viral and virus–host interactions are merged to create a unified interaction network indicating the types of proteins; the size of a node reflects the node degree. The SARS-CoV-2 interactions that are inferred from SARS-CoV are represented by green edges, with stars indicating the suspected disruption of the interaction based on the evolutionary conservation of the binding sites. The loops correspond to homo-oligomeric interactions. (B) Structural modeling prediction of interaction between SARS-CoV-2 S protein and three monoclonal antibodies.
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