tetano
Editor, Senior Moderator
Precis Clin Med
. 2021 Aug 28;4(4):215-230.
doi: 10.1093/pcmedi/pbab022. eCollection 2021 Dec.
Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications
Zhihan Wang[SUP] 1 [/SUP], Kai Guo[SUP] 2 [/SUP], Pan Gao[SUP] 1 [/SUP], Qinqin Pu[SUP] 1 [/SUP], Changlong Li[SUP] 3 [/SUP], Junguk Hur[SUP] 1 [/SUP], Min Wu[SUP] 1 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. The lack of time for new drug discovery and the urgent need for rapid disease control to reduce mortality have led to a search for quick and effective alternatives to novel therapeutics, for example drug repurposing. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from patients with mild and severe COVID-19 (GEO: GSE145926, public data available and accessed on 22 April 2020). We identified 281 FDA-approved drugs that have the potential to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested and demonstrated the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a, two chemical inhibitors of glycosylation (a post-translational modification) on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus as well as on the transcription and translation of host cell cytokines and their regulators (IFNs and ISGs). In conclusion, we have identified and experimentally validated repurposable anti-SARS-CoV-2 and IAV drugs using a systems biology approach, which may have the potential for treating these viral infections and their complications (sepsis).
Keywords: COVID-19; Library of Integrated Network-Based Cellular Signatures; SARS-CoV-2; adverse drug reaction; drug repurposing; influenza; post-transcription modifications; sepsis; single-cell RNA sequencing.
. 2021 Aug 28;4(4):215-230.
doi: 10.1093/pcmedi/pbab022. eCollection 2021 Dec.
Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications
Zhihan Wang[SUP] 1 [/SUP], Kai Guo[SUP] 2 [/SUP], Pan Gao[SUP] 1 [/SUP], Qinqin Pu[SUP] 1 [/SUP], Changlong Li[SUP] 3 [/SUP], Junguk Hur[SUP] 1 [/SUP], Min Wu[SUP] 1 [/SUP]
Affiliations
- PMID: 34993416
- PMCID: PMC8694063
- DOI: 10.1093/pcmedi/pbab022
Abstract
Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. The lack of time for new drug discovery and the urgent need for rapid disease control to reduce mortality have led to a search for quick and effective alternatives to novel therapeutics, for example drug repurposing. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from patients with mild and severe COVID-19 (GEO: GSE145926, public data available and accessed on 22 April 2020). We identified 281 FDA-approved drugs that have the potential to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested and demonstrated the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a, two chemical inhibitors of glycosylation (a post-translational modification) on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus as well as on the transcription and translation of host cell cytokines and their regulators (IFNs and ISGs). In conclusion, we have identified and experimentally validated repurposable anti-SARS-CoV-2 and IAV drugs using a systems biology approach, which may have the potential for treating these viral infections and their complications (sepsis).
Keywords: COVID-19; Library of Integrated Network-Based Cellular Signatures; SARS-CoV-2; adverse drug reaction; drug repurposing; influenza; post-transcription modifications; sepsis; single-cell RNA sequencing.