SARS-CoV2 associated secretion of nanoLuciferase reports on virus and Virus-Like Particle production

Abstract

SARS-CoV2 is a positive-strand RNA virus in the Coronaviridae family that has caused world-wide morbidity and mortality. While much progress has been made we still need expanded rapid anti-virals. The top advanced antiviral candidates all target stages of RNA replication, leaving virus assembly an unexplored avenue of antiviral research. To address this gap, and explore the biochemical and cell biological features of viral assembly, we have employed an improved virus-like particle (VLP) system. We exploited the small nanoLuciferase protein for enhanced signal and surprisingly found that the protein itself appears to be packaged into both SARS CoV2 VLPs and virions and secreted from cells. Interestingly, nLuc is not co-secreted with dengue or Zika infection, suggesting the large virion of Coronavirus can encaspidate and secrete a cellularly expressed reporter protein. Our findings open the way for powerful new approaches to measure viral particle production, egress and viral entry mechanisms.