A Single-Cell Network-Based Drug Repositioning Strategy for Post-COVID-19 Pulmonary Fibrosis

Abstract

Post-COVID-19 pulmonary fibrosis (PCPF) is a long-term complication that appears in some COVID-19 survivors. However, there are currently limited options for treating PCPF patients. To address this problem, we investigated COVID-19 patients’ transcriptome at single-cell resolution and combined biological network analyses to repurpose the drugs treating PCPF. We revealed a novel gene signature of PCPF. The signature is functionally associated with the viral infection and lung fibrosis. Further, the signature has good performance in diagnosing and assessing pulmonary fibrosis. Next, we applied a network-based drug repurposing method to explore novel treatments for PCPF. By quantifying the proximity between the drug targets and the signature in the interactome, we identified several potential candidates and provided a drug list ranked by their proximity. Taken together, we revealed a novel gene expression signature as a theragnostic biomarker for PCPF by integrating different computational approaches. Moreover, we showed that network-based proximity could be used as a framework to repurpose drugs for PCPF.

Keywords

• single-cell RNA sequencing
• COVID-19
• pulmonary fibrosis
• biological networks
• drug repurposing