Identifying existing drugs with anti-COVID effects

Key Messages

This computational study analyzed genetic makeup of SARS-CoV-2 infected cells to identify the most promising existing drugs that may be repurposed to treat or prevent COVID-19.

46 already-existing drugs were shown to have properties that target the drivers of SARS-CoV-2 infection.

The study identified the cytokine CXCL10 as a vital target for treating COVID-19.

The anti-cholesterol drug fenofibrate reduces CXCL10 activity, thus making it an important candidate for treating COVID-19.

PLOS ONE

Publication Date: September 28, 2021
Peer Reviewed: Yes
Publication Type: Original | Theoretical
DOI: https://www.doi.org/10.1371/journal.pone.0257784

Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium

Rajaneesh K. Gupta, Enyinna L. Nwachuku, Benjamin E. Zusman, Ruchira M. Jha, Ava M. Puccio

Abstract

Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature’-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.