Identification and validation of Triamcinolone and Gallopamil as treatments for early COVID-19 via an in silico repurposing pipeline

MacMahon, M'eabh; Hwang, Woochang; Yim, Soorin; MacMahon, Eoghan; Abraham, Alexandre; Barton, Justin; Tharmakulasingam, Mukunthan; Bilokon, Paul; Gaddi, Vasanthi Priyadarshini; Han, Namshik

SARS-CoV-2, the causative virus of COVID-19 continues to cause an ongoing global pandemic. Therapeutics are still needed to treat mild and severe COVID-19. Drug repurposing provides an opportunity to deploy drugs for COVID-19 more rapidly than developing novel therapeutics. Some existing drugs have shown promise for treating COVID-19 in clinical trials. This in silico study uses structural similarity to clinical trial drugs to identify two drugs with potential applications to treat early COVID-19. We apply in silico validation to suggest a possible mechanism of action for both. Triamcinolone is a corticosteroid structurally similar to Dexamethasone. Gallopamil is a calcium channel blocker structurally similar to Verapamil. We propose that both these drugs could be useful to treat early COVID-19 infection due to the proximity of their targets within a SARS-CoV-2-induced protein-protein interaction network to kinases active in early infection, and the APOA1 protein which is linked to the spread of COVID-19.