CovInter: interaction data between coronavirus RNAs and host proteins

Abstract

Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity. In other words, there is an urgent need to develop a database for providing such IVRHP data. In this study, a new database was therefore constructed to describe the interactions between coronavirus RNAs and host proteins (CovInter). This database is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins. Given the devastating and persistent threat of coronaviruses, CovInter is highly expected to fill the gap in the whole process of the 'molecular arms race' between viruses and their hosts, which will then aid in the discovery of new antiviral therapies. It's now free and publicly accessible at: https://idrblab.org/covinter/.

Graphical Abstract

CovInter is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins.

Figure 1.

A schematic representation of the life cycle of coronavirus, which consisted of multiple steps (such as fusion, proteolysis, translation, replication, packaging & release). The interactions between virus RNAs and host proteins (IVRHPs, highlighted using blue bold font) are unique in representing not only the virus’ attempts to accelerate their translation & replication, but also the host's endeavor to combat virus pathogenicity.

Figure 2.

A typical CovInter page for virus RNA describing a comprehensive list of host proteins that interacted with this RNA. The detailed experimental information was provided and explicitly discussed, which included the virus infection time, infection cell, cell-originated tissue, detection method, interaction types, interaction binding type and so on. All the interactions were validated using diverse living systems including 30 cell lines from 14 tissues and various model organisms. Detailed information of the interacting proteins can be found by clicking the dark blue button.

Figure 3.

A typical circular plot in online CovInter comprehensively describing all IVRHPs for a particular RNA region from the France/IDF-220–95 stain of SARS-CoV-2 (indicated by a red circle). All interactions between this RNA and different host proteins (green circles) were visualized by linking them using the red line. Other RNAs (from other SARS-CoV-2 strains) which interacted with the same host proteins as that of the studied RNA region above, were highlighted by orange circles, and their corresponding interactions with host proteins were visualized using orange lines. The diameter of a green circle indicated the number of virus’ RNAs interacting with the corresponding protein. The larger the diameter of a protein is, the more virus RNAs this protein interacts with. Specifically, the diameter of a green circle denoted the level of conservation among the corresponding IVRHPs of different virus variants/strains. The circular plot is drawn using the Pychart 1.91 package in Python 3.8 environment, which can be readily viewed online and freely downloaded from the CovInter website.

Figure 4.

A typical hierarchical plot in CovInter illustrating all IVRHPs for specific host protein named ‘RPS3’ (on the far-left side). All interactions between virus RNAs (as provided in the middle column) and this protein were described by linking them using purple line. The strains of the same type of coronaviruses were illustrated in the same color on the right side (e.g. all SARS-CoV-2 strains were shown using blue lines one right side). As illustrated, the IVRHPs between virus 5′-UTR RNA and host RPS3 protein were substantially conserved among different SARS-CoV-2 strains, but this type of IVRHP has not been found in other types of coronaviruses. Different from the 5′-UTR RNA, the 3′-UTR RNA was reported to be conserved among different coronavirus types (highlighted using different colors). The hierarchical plot above is drawn using the Pychart 1.91 package in the Python 3.8 environment, which can be readily viewed online and freely downloaded from the CovInter website.

Figure 5.

A typical CovInter webpage showing the biological function and molecular regulation data of the host interacting proteins. A total of 808 host proteins were offered in CovInter as pro-viral (facilitating viral infection) and anti-viral (hampering infectious progression). The detailed experiments for validating the protein function were described here, such as infection time/cells, cell-originated tissue, detection method and so on. Moreover, the available molecular regulators (especially drugs) of the host protein were collected, which resulted in a total of 391 drugs targeting 110 host proteins. All data can be freely downloaded from the CovInter website.

Figure 6.

Differential expression patterns of host interacting proteins illustrated in CovInter. The differential expression pattern data were collected using the following process. First, three benchmarks were collected from GEO (GSE152641, GSE162835 and GSE175779). GSE152641 is composed of 24 and 62 blood samples before and after SARS-COV-2 infections; GSE162835 consists of the nasopharyngeal swab samples of 37, 10 and 3 patients with mild, moderate, and severe symptom, respectively; GSE175779 contains the bronchial epithelial cell samples from 4 healthy people and 4 SARS-COV-2 patients at different time points (0, 24, 48, 72 and 96 h). Second, the differential expression pattern of host proteins was collected from the original studies of these benchmarks and illustrated in CovInter using the Seaborn 0.11.2 package in Python. Green: protein expression in healthy individuals; red: protein expression in the infected patients. Mild: protein expression in patients with mild symptom; Moderate: protein expression in patients with moderate symptom; Severe: protein expression in patients with severe symptom.