Remdesivir: Investigational Antiviral Drug with Activity Against Ebola and Other Emerging and Neglected Viruses

Abstract

The World Health Organization (WHO) has identified key viral pathogens that are high priority for research and development because of the potential for a major public health emergency with limited options to contain future outbreaks. Pathogens on the list include filoviruses (Ebola virus [EBOV]; Marburg virus [MARV]), coronaviruses (Middle East respiratory syndrome coronavirus [MERS-CoV], severe acute respiratory syndrome coronavirus [SARS-CoV]), paramyxoviruses (Nipah virus and Hendra virus), as well as other RNA virus families. Remdesivir (formerly GS-5734) is a single diastereomer monophosphoramidate prodrug of an adenine nucleoside analog that has potent, broad spectrum activity against filoviruses, coronaviruses, and paramyxoviruses. In vivo, remdesivir increased survival and/or attenuated disease burden and viral load in animals infected with EBOV, MARV, MERS-CoV, SARS-CoV, or Nipah virus even when the treatment initiation was delayed by several days post-infection. In nonhuman primate studies, remdesivir distributed into the genital tract, eyes, and to some extent the brain following intravenous administration, suggesting potential for antiviral effects in viral sanctuary sites. An ongoing clinical trial is investigating whether remdesivir can clear viral RNA from male survivors of Ebola virus disease (EVD) whose semen continued to be positive for EBOV. Remdesivir is currently undergoing investigation in a randomized controlled trial for the treatment of acute EVD in the Democratic Republic of the Congo. The drug product is also available for compassionate use treatment and post-exposure prophylaxis of the relevant viral infections. Importantly, the remdesivir drug product is available in a stable lyophilized formulation with a long shelf-life without reliance on cold chain infrastructure.