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Journal Article Ppublish 5 citations

PubMed: 37597114 DOI: 10.1007/s40199-023-00471-1

COVID-19: A novel holistic systems biology approach to predict its molecular mechanisms (in vitro) and repurpose drugs.

Daru 31(2):155-171

Authors: Marzieh Sameni, Seyed Amir Mirmotalebisohi, Sadaf Dadashkhan, Sepideh Ghani, Maryam Abbasi, Effat Noori, Hakimeh Zali

Affiliations

  • Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Molecular Medicine Research Center, Universitätsklinikum Jena, Jena, Germany.
  • Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. Zhino-Gene Research Services Co. Tehran, Iran.
  • Proteomics Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.
  • Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

PURPOSE

COVID-19 strangely kills some youth with no history of physical weakness, and in addition to the lungs, it may even directly harm other organs. Its complex mechanism has led to the loss of any significantly effective drug, and some patients with severe forms still die daily. Common methods for identifying disease mechanisms and drug design are often time-consuming or reductionist. Here, we use a novel holistic systems biology approach to predict its molecular mechanisms (in vitro), significant molecular relations with SARS, and repurpose drugs.

METHODS

We have utilized its relative phylogenic similarity to SARS. Using the available omics data for SARS and the fewer data for COVID-19 to decode the mechanisms and their significant relations, We applied the Cytoscape analyzer, MCODE, STRING, and DAVID tools to predict the topographically crucial molecules, clusters, protein interaction mappings, and functional analysis. We also applied a novel approach to identify the significant relations between the two infections using the Fischer exact test for MCODE clusters. We then constructed and analyzed a drug-gene network using PharmGKB and DrugBank (retrieved using the dgidb).

RESULTS

Some of the shared identified crucial molecules, BPs and pathways included Kaposi sarcoma-associated herpesvirus infection, Influenza A, and NOD-like receptor signaling pathways. Besides, our identified crucial molecules specific to host response against SARS-CoV-2 included FGA, BMP4, PRPF40A, and IFI16.

CONCLUSION

We also introduced seven new repurposed candidate drugs based on the drug-gene network analysis for the identified crucial molecules. Therefore, we suggest that our newly recommended repurposed drugs be further investigated in Vitro and in Vivo against COVID-19.

MeSH

Genes, Gene Regulatory Networks, Pharmaceutical Preparations, Systems Biology, Covid-19, Pharmacology, Herpesvirus 8, Human, Infections, Nlr Proteins

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