Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection

TLDR

Emerging infections force clinicians to choose treatments rapidly, often leaving only supportive care or untested plasma, making repurposing existing drugs the most viable option. The study aims to evaluate repurposing approved drugs as a rapid therapeutic strategy for emerging viral outbreaks. The authors screened 290 FDA‑approved or advanced‑clinical‑development compounds for activity against MERS‑CoV and SARS‑CoV, focusing on drugs with defined cellular targets. They identified 27 dual‑virus active compounds across 13 classes, such as estrogen‑receptor inhibitors and dopamine‑receptor antagonists, providing new targets for in vivo and clinical research.

Abstract

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.