Drugs which have the potential for treating COVID-19 are identified by analysis of the interactome in SARS-CoV-2 infected cells.

Key Messages

This study used computer analysis to identify existing drugs which have the potential to be repurposed for treating COVID–19

In cell biology, the “interactome” is the complete set of interactions which occurs between all the molecules in the cell. By analyzing the interactome of cells infected with SARS-CoV-2, together with changes in gene activity caused by treating infected cells with 56 different drugs, 24 drugs, including fenofibrate, were identified as potential candidates for repurposing.

Each of the drugs has proven antiviral activity against cells infected with SARS-CoV–2 in the laboratory and were already being tested for their clinical activity against COVID-19. They are broad-spectrum antiviral drugs which were also identified and prioritized by other computational re-purposing studies and they have proven antiviral activity against the SARS-CoV and MERS-CoV corona viruses in addition to SARS-CoV-2.

The use of fenofibrate as a repurposed drug for treating COVID-19 is already supported by evidence in the literature.

In addition, fenofibrate provided neuroprotection against Japanese encephalitis in a mouse model studying viral infection.

Fenofibrate treatment activated genes that detoxified pro-inflammatory molecules called leukotrienes, it reduced microglial cell activation which promotes neuroinflammation and reduced the levels of chemokines and cytokines, which are small proteins that promote inflammation.

This study supports a role for fenofibrate in treating the inflammation associated with severe COVID-19, including inflammation of the brain.

Research Square

Publication Date: May 28, 2020
Peer Reviewed: No
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.21203/rs.3.rs-30363/v1

Potentially repurposable drugs for COVID-19 identified from SARS-CoV-2 Host Protein Interactome

Kalyani B. Karunakaran, N. Balakrishnan, Madhavi Ganapathiraju

Abstract

We previously presented the protein-protein interaction network – the ‘HoP’ or the host protein interactome – of 332 host proteins that were identified to interact with 27 nCoV19 viral proteins by Gordon et al. Here, we studied drugs targeting the proteins in this interactome to identify whether any of them may potentially be repurposable against SARS-CoV-2. We studied each of the drugs using the BaseSpace Correlation Engine and identified those that induce gene expression profiles negatively correlated with SARS-associated expression profile. This analysis resulted in 20 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for SARS (viral infection versus normal). These included drugs that were already being tested for their clinical activity against SARS-CoV-2, those with proven activity against SARS-CoV/MERS-CoV, broad-spectrum antiviral drugs, and those identified/prioritized by other computational re-purposing studies. In summary, our integrated computational analysis of the HoP interactome in conjunction with drug-induced transcriptomic data resulted in drugs that may be repurposable for COVID-19.