Nucleoside analogs NM107 and AT-527 are antiviral against rubella virus

Abstract

Rubella is a highly contagious viral infection that usually causes a mild disease in children and adults. However, infection during pregnancy can result in a fetal or newborn death or congenital rubella syndrome (CRS), a constellation of permanent birth defects including cataracts, heart defects, and sensorineural deafness. The live-attenuated rubella vaccine has been highly effective with the Americas declared free of endemic rubella transmission in 2015. However, rubella remains a significant problem worldwide and the leading cause of vaccine-preventable birth defects globally. Thus, elimination of rubella and CRS is a goal of the World Health Organization. There exist no specific therapeutics approved for rubella virus. Therefore, we set out to identify whether existing small molecules may be repurposed for use against rubella virus infection. Thus, we performed a high-throughput screen for small molecules active against rubella virus in human respiratory cells and identified two nucleoside analogs, NM107 and AT-527, with potent antiviral activity. Furthermore, we found that combining these nucleoside analogs with inhibitors of host nucleoside biosynthesis had synergistic antiviral activity. These studies open the door to new potential approaches to treat rubella infections.

Surveillance for rubella virus in samples obtained from non‐immunodeficient individuals

“…8 Recently, a class of nucleoside analogs appeared to have efficacy against RuV, leading to the possibility of a direct antiviral approach to treatment. 11 Identifying optimal treatment requires a firm understanding of the pathogenesis and the variables governing VDRV-associated inflammatory disease.…”