Recently, Novartis disclosed a new class of brain-penetrant, covalent agents against kinetoplastid parasites in Science. Kinetoplastid parasites cause Chagas disease (T. cruzi), sleeping sickness (T. brucei), and leishmaniasis (Leishmania), but there are few effective treatment options, especially for infections in the brain (e.g. stage II sleeping sickness).

The Janssen pan-genotype, pan-serotype dengue virus inhibitor, JNJ-A07 , demonstrates broad activity against a panel of 21 clinical isolates and has a high barrier to resistance. It blocks the interaction between the non-enzymatic NS4B protein and NS3, preventing them from forming an NS3-NS4B complex which is essential for replication (though [...]

AL-611 is a prodrug to a nucleoside inhibitor of HCV NS5B polymerase. While there have been very successful nucleoside drugs (e.g. sofosbuvir), several nucleoside inhibitors of HCV previously failed in the clinic due to severe toxicities, in some cases due to incorporation of the nucleosides into host RNA. The Janssen Biopharma (formerly [...]

The Gilead SARS-CoV-2 drug, GS-621763, is an oral prodrug of the parent nucleoside of remdesivir (GS-441524) which demonstrated therapeutic and prophylactic efficacy in a ferret model of SARS-CoV-2 infection, significantly reducing viral load to near-undetectable levels with twice-daily administration. Remdesivir is already FDA [...]

ASP5286 is an analog of the natural product cyclosporin A that maintains the anti-HCV activity of cyclosporin A by binding to cyclophilin, but was optimized to be less immunosuppresive than cyclosporin A. The macrocycle was identified through semisynthetic derivitization of a related natural product, FR901459. The Astellas team was able to [...]