Immune-Related Protein Interaction Network in Severe COVID-19 Patients toward the Identification of Key Proteins and Drug Repurposing

Pakorn Sagulkoo; Apichat Suratanee; Kitiporn Plaimas

doi:10.3390/biom12050690

Immune-Related Protein Interaction Network in Severe COVID-19 Patients toward the Identification of Key Proteins and Drug Repurposing

Biomolecules. 2022 May 11;12(5):690. doi: 10.3390/biom12050690.

Authors

Pakorn Sagulkoo^{1

2}, Apichat Suratanee^{3

4}, Kitiporn Plaimas^{5

6}

Affiliations

¹ Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
² Center of Biomedical Informatics, Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
³ Department of Mathematics, Faculty of Applied Science, King Mongkut's University of Technology North Bangkok, Bangkok 10800, Thailand.
⁴ Intelligent and Nonlinear Dynamics Innovations Research Center, Science and Technology Research Institute, King Mongkut's University of Technology North Bangkok, Bangkok 10800, Thailand.
⁵ Advance Virtual and Intelligent Computing (AVIC) Center, Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
⁶ Omics Science and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.

Abstract

Coronavirus disease 2019 (COVID-19) is still an active global public health issue. Although vaccines and therapeutic options are available, some patients experience severe conditions and need critical care support. Hence, identifying key genes or proteins involved in immune-related severe COVID-19 is necessary to find or develop the targeted therapies. This study proposed a novel construction of an immune-related protein interaction network (IPIN) in severe cases with the use of a network diffusion technique on a human interactome network and transcriptomic data. Enrichment analysis revealed that the IPIN was mainly associated with antiviral, innate immune, apoptosis, cell division, and cell cycle regulation signaling pathways. Twenty-three proteins were identified as key proteins to find associated drugs. Finally, poly (I:C), mitomycin C, decitabine, gemcitabine, hydroxyurea, tamoxifen, and curcumin were the potential drugs interacting with the key proteins to heal severe COVID-19. In conclusion, IPIN can be a good representative network for the immune system that integrates the protein interaction network and transcriptomic data. Thus, the key proteins and target drugs in IPIN help to find a new treatment with the use of existing drugs to treat the disease apart from vaccination and conventional antiviral therapy.

Keywords: drug repurposing; immune system; network diffusion; protein-protein interaction network; severe COVID-19.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use
COVID-19 Drug Treatment*
Drug Repositioning
Humans
Protein Interaction Maps*
Signal Transduction
Transcriptome

Substances

Antiviral Agents

Grants and funding

This research was funded by the National Science, Research and Innovation Fund (NSRF), and King Mongkut’s University of Technology North Bangkok with Contract no. KMUTNB-FF-65-55.