An in silico drug repurposing pipeline to identify drugs with the potential to inhibit SARS-CoV-2 replication

TL;DR

This study presents an in silico pipeline to identify existing drugs that could potentially inhibit SARS-CoV-2 replication, aiding rapid drug repurposing efforts during the COVID-19 pandemic.

Contribution

The paper introduces a structural similarity-based in silico method to predict and analyze drugs for repurposing against COVID-19, identifying two promising candidates.

Findings

Identified two drugs, triamcinolone and gallopamil, with potential to inhibit SARS-CoV-2.

Mechanism of action analysis supports their possible role in viral inhibition.

Demonstrates effectiveness of in silico approaches for quick drug repurposing.

Abstract

Drug repurposing provides an opportunity to redeploy drugs, which ideally are already approved for use in humans, for the treatment of other diseases. For example, the repurposing of dexamethasone and baricitinib has played a crucial role in saving patient lives during the ongoing SARS-CoV-2 pandemic. There remains a need to expand therapeutic approaches to prevent life-threatening complications in patients with COVID-19. Using an in silico approach based on structural similarity to drugs already in clinical trials for COVID-19, potential drugs were predicted for repurposing. For a subset of identified drugs with different targets to their corresponding COVID-19 clinical trial drug, a mechanism of action analysis was applied to establish whether they might have a role in inhibiting the replication of SARS-CoV-2. Of sixty drugs predicted in this study, two with the potential to inhibit SARS-CoV-2 replication were identified using mechanism of action analysis. Triamcinolone is a corticosteroid that is structurally similar to dexamethasone; gallopamil is a calcium channel blocker that is structurally similar to verapamil. In silico approaches indicate possible mechanisms of action for both drugs in inhibiting SARS-CoV-2 replication. The identification of these drugs as potentially useful for patients with COVID-19 who are at a higher risk of developing severe disease supports the use of in silico approaches to facilitate quick and cost-effective drug repurposing. Such drugs could expand the number of treatments available to patients who are not protected by vaccination.