Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective

• Published in: International journal of biological macromolecules 2020-11, Vol.163, p.1-8
• Main Authors: Prasad, Kartikay, Khatoon, Fatima, Rashid, Summya, Ali, Nemat, AlAsmari, Abdullah F., Ahmed, Mohammad Z., Alqahtani, Ali S., Alqahtani, Mohammed S., Kumar, Vijay
• Format: Article
• Language: English
• Subjects: A549 Cells; Antiviral Agents - pharmacology; Betacoronavirus - genetics; Betacoronavirus - immunology; Coronavirus Infections - genetics; Coronavirus Infections - immunology; Coronavirus Infections - virology; COVID-19; Drug Repositioning; Drug repurposing; ELAV-Like Protein 2 - genetics; ELAV-Like Protein 2 - immunology; ELAV-Like Protein 2 - metabolism; Gene Regulatory Networks; Humans; Immune response; Immunity, Innate; Interferon stimulating genes; Interferon-gamma - immunology; Interferon-gamma - pharmacology; Network biology; Pandemics; Pneumonia, Viral - genetics; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; Protein Interaction Maps - genetics; SARS-CoV-2; Signal Transduction; Transcriptome
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.06.228

The current pandemic of 2019 novel coronavirus disease (COVID-19) caused by a novel virus strain, 2019-nCoV/SARS-CoV-2 have posed a serious threat to global public health and economy. It is largely unknown how the human immune system responds to this infection. A better understanding of the immune response to SARS-CoV-2 will be important to develop therapeutics against COVID-19. Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and employed a network biology approach to generate human-virus interactome. Network topological analysis discovers 15 SARS-CoV-2 targets, which belongs to a subset of interferon (IFN) stimulated genes (ISGs). These ISGs (IFIT1, IFITM1, IRF7, ISG15, MX1, and OAS2) can be considered as potential candidates for drug targets in the treatments of COVID-19. We have identified significant interaction between ISGs and TLR3 agonists, like poly I: C, and imiquimod, and suggests that TLR3 agonists can be considered as a potential drug for drug repurposing in COVID-19. Our network centric analysis suggests that moderating the innate immune response is a valuable approach to target COVID-19. •Differential gene expression analysis of SARS-CoV-2 infected transcriptome•Network based Human-SRAS-CoV-2 interactome analysis•Interferon (IFN) stimulated genes (ISGs) are the most important targets.•TLR3 agonists, like poly I:C, and imiquimod are identified as potential drugs.•Targeting the innate immune response is a valuable approach against COVID-19.