Yili Xu

TL;DR: These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates, and the broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenavirus, and coronavirus suggests the potential for wider medical use.

TL;DR: A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model and structure activity relationships established that the 1′-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases.

TL;DR: It is shown that in addition to the properties already known for LEDGINs, the binding of tBPQAs to the IN dimer interface inhibits IN enzymatic activity in a LEDGF-independent manner, and this inhibition occurs at or prior to the viral DNA 3′-processing step.

TL;DR: The paradigm reported here should facilitate development of ribonucleosides with a lower potential for toxicity, and suggest the possibility that patients exhibiting adverse effects during clinical trials may be more susceptible to damage by nucleoside analogs because of defects in mitochondrial or nuclear transcription.

TL;DR: In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF.