Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep 3;21(1):65.
doi: 10.1186/s40360-020-00444-z.

A protein interaction map identifies existing drugs targeting SARS-CoV-2

Claudia Cava  1 , Gloria Bertoli  2 , Isabella Castiglioni  3
Affiliations

A protein interaction map identifies existing drugs targeting SARS-CoV-2

Claudia Cava et al. BMC Pharmacol Toxicol. .

Abstract

Background: Severe acute respiratory syndrome coronavirus (SARS-CoV-2), an emerging Betacoronavirus, is the causative agent of COVID-19. Angiotensin converting enzyme 2 (ACE2), being the main cell receptor of SARS-CoV-2, plays a role in the entry of the virus into the cell. Currently, there are neither specific antiviral drugs for the treatment or preventive drugs such as vaccines.

Methods: We proposed a bioinformatics analysis to test in silico existing drugs as a fast way to identify an efficient therapy. We performed a differential expression analysis in order to identify differentially expressed genes in COVID-19 patients correlated with ACE-2 and we explored their direct relations with a network approach integrating also drug-gene interactions. The drugs with a central role in the network were also investigated with a molecular docking analysis.

Results: We found 825 differentially expressed genes correlated with ACE2. The protein-protein interactions among differentially expressed genes identified a network of 474 genes and 1130 interactions.

Conclusions: The integration of drug-gene interactions in the network and molecular docking analysis allows us to obtain several drugs with antiviral activity that, alone or in combination with other treatment options, could be considered as therapeutic approaches against COVID-19.

Keywords: COVID-19; Drug; In silico analysis; Molecular docking; Network; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
a Volcano plot for differential gene expression. The dots represent the genes that are related to p-value versus fold change. Red dots are genes that are significantly up-regulated in Covid-19, and green dots are genes significantly down-regulated in Covid-19. b Top enriched KEGG pathways. The size of the circles represents the number of differentially expressed gene in the pathway. The color intensity of the circle represents the p-value
Fig. 2
Fig. 2
a Protein-protein and drug-protein interactions consisting of 474 proteins and 714 drugs. Intensity colour of nodes represents the degree centrality. b Drugs with the highest degree centrality in the network. c Proteins with the highest degree centrality in the network. d Barplot indicating the number of nodes for each community
Fig. 3
Fig. 3
Community detection. The figure shows the biggest communities identified a first community, b second community, c third community. Proteins with higher degree centrality are represented with the purple circles. Drugs are represented with light-blue triangle (we removed the nodes that have only one connection)
Fig. 4
Fig. 4
Docking interactions of a puromycin with PDB ID 5R82 and b anisomycin with PDB ID 5R7Z
See this image and copyright information in PMC

References

    1. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020. 10.1038/s41586-020-2286-9. - PMC - PubMed
    1. Matricardi PM, Dal Negro RW, Nisini R. The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures. Pediatr Allergy Immunol. 2020. 10.1111/pai.13271. - PMC - PubMed
    1. Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503(7477):535–538. doi: 10.1038/nature12711. - DOI - PMC - PubMed
    1. Cava C, Bertoli G, Castiglioni I. In silico discovery of candidate drugs against Covid-19. Viruses. 2020;12(4). 10.3390/v12040404. - PMC - PubMed
    1. Jawhara S. Could intravenous immunoglobulin collected from recovered coronavirus patients protect against COVID-19 and strengthen the immune system of new patients? Int J Mol Sci. 2020;21(7). 10.3390/ijms21072272. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources