Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections. Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.
【저자키워드】 viral infection, Drug development, viral pathogenesis, Antiviral agents, 【초록키워드】 Treatment, Efficacy, Human, Ritonavir, Remdesivir, combination therapy, in vitro, antiviral activity, Prophylactic, MERS-CoV, Saudi Arabia, antiviral drug, Pulmonary function, infections, Viral load, mice, therapeutic, death, virus replication, in vivo, disease, parameters, RDV, Evidence, Combination, Middle East, interferon beta, MERS coronavirus, severe respiratory disease, Kingdom, human infection, treat, respiratory syndrome coronavirus, MERS-CoV infection, lung viral load, country, Ifnb, severe lung pathology, IMPROVE, evaluated, approved, reduce, RTV, LPV, LPV/RTV-IFNb, not reduce, 【제목키워드】 Ritonavir, Remdesivir, MERS-CoV, Combination, interferon beta, Comparative, therapeutic efficacy,