Drug combination therapy for emerging viral diseases.

Effective therapeutics to combat emerging viral infections are an unmet need. Historically, treatments for chronic viral infections with single drugs have not been successful, as exemplified by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Combination therapy for these diseases has led to improved clinical outcomes with dramatic reductions in viral load, morbidity, and mortality. Drug combinations can enhance therapeutic efficacy through additive, and ideally synergistic, effects for emerging and re-emerging viruses, such as influenza, severe acute respiratory syndrome-coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS)-CoV, Ebola, Zika, and SARS-coronavirus 2 (CoV-2). Although novel drug development through traditional pipelines remains a priority, in the interim, effective synergistic drug candidates could be rapidly identified by drug-repurposing screens, facilitating accelerated paths to clinical testing and potential emergency use authorizations.

Drug Discovery Strategies for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is a novel disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus that was first detected in December of 2019 in Wuhan, China, and has rapidly spread worldwide. The search for a suitable vaccine as well as effective therapeutics for the treatment of COVID-19 is underway. Drug repurposing screens provide a useful and effective solution for identifying potential therapeutics against SARS-CoV-2. For example, the experimental drug remdesivir, originally developed for Ebola virus infections, has been approved by the US Food and Drug Administration as an emergency use treatment of COVID-19. However, the efficacy and toxicity of this drug need further improvements. In this review, we discuss recent findings on the pathology of coronaviruses and the drug targets for the treatment of COVID-19. Both SARS-CoV-2-specific inhibitors and broad-spectrum anticoronavirus drugs against SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV-2 will be valuable additions to the anti-SARS-CoV-2 armament. A multitarget treatment approach with synergistic drug combinations containing different mechanisms of action may be a practical therapeutic strategy for the treatment of severe COVID-19. SIGNIFICANCE STATEMENT: Understanding the biology and pathology of RNA viruses is critical to accomplish the challenging task of developing vaccines and therapeutics against SARS-CoV-2. This review highlights the anti-SARS-CoV-2 drug targets and therapeutic development strategies for COVID-19 treatment.