Comparison of Dose-Response Relationships for Two Isolates of SARS-CoV-2 in a Nonhuman Primate Model of Inhalational COVID-19.

As the COVID-19 pandemic has progressed, numerous variants of SARS-CoV-2 have arisen, with several displaying increased transmissibility. The present study compared dose-response relationships and disease presentation in nonhuman primates infected with aerosols containing an isolate of the Gamma variant of SARS-CoV-2 to the results of our previous study with the earlier WA-1 isolate of SARS-CoV-2. Disease in Gamma-infected animals was mild, characterized by dose-dependent fever and oronasal shedding of virus.

Inhibition of phosphatidylinositol-3-kinase by the furanosesquiterpenoid hibiscone C.

The phosphatidylinositol-3-kinase (PIK) pathway regulates cellular metabolism and is upregulated in many cancers, making it an attractive chemotherapeutic target. Wortmannin is a potent inhibitor of PIK; however, its potential as a chemotherapeutic is limited due to its instability, lack of selectivity, and lengthy chemical synthesis. In contrast, hibiscone C, a structurally simpler and less studied member of the furanosteroid family, has been expediently prepared by total synthesis.