Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for...

Area of Science:

• Virology and Immunology
• Drug Discovery and Repurposing
• Computational Biology

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 necessitates urgent identification of therapeutic targets.
• SARS-CoV-2 infection leads to significant morbidity and mortality, highlighting the need for effective treatments.
• The SARS-CoV ΔORF6 mutant serves as a surrogate model due to shared interferon antagonistic pathway deficiencies.

Purpose of the Study:

• To identify potential therapeutic targets for COVID-19 by analyzing gene expression profiles.
• To reposition existing medications for COVID-19 therapy using a SARS-CoV surrogate model.
• To discover novel drug groups for mitigating SARS-CoV-2 infection symptoms.

Main Methods:

• Analysis of temporal profiles of upregulated genes in Calu-3 cells infected with the SARS-CoV ΔORF6 mutant.
• Prioritization of 55 genes and 238 ligands for drug repositioning.
• Utilized the Anatomical Therapeutic Chemical (ATC) classification system to identify drug groups.

Main Results:

• Identified 55 key genes and 238 ligands involved in the host response to SARS-CoV infection.
• Eight drugs, including dexamethasone, ritonavir, and baricitinib, were prioritized and are currently in clinical trials for COVID-19.
• Pinpointed 16 drug groups within the ATC system with potential therapeutic value for COVID-19.

Conclusions:

• The SARS-CoV ΔORF6 mutant model effectively aids in identifying therapeutic strategies for COVID-19.
• Drug repositioning using this approach can accelerate the development of treatments for SARS-CoV-2 infection.
• The study provides a rational basis for repurposing existing drugs and drug classes to combat the COVID-19 pandemic.