CDI (Clostridioides difficile) infection is a leading cause of healthcare-associated diarrhea with significant morbidity and mortality, and with the rise of hypervirulent and resistant strains, novel and selective antibiotics to treat these infections are needed. Cadazolid, a hybrid antibiotic that combines pharmacophores of two classes of antibacterials, demonstrated potent activity in vitro against relevant C. difficile strains, while avoiding native gut flora. Additionally, the compound was designed to be gut-restricted, with minimal systemic circulation following PO dosing.

AM-2-19 (SF001) is an analog of the notoriously toxic IV antifungal drug, amphotericin B (AmB). Compared with AmB, AM-2-19 is significantly less toxic against primary human cells and in mice, while more broadly active against fungal pathogens including antifungal drug-resistant strains. SF001 received Fast-Track Designation from the FDA in 2023 and has progressed to Ph. I clinical development. This article highlights the history of antifungal polyene natural products, a new mechanistic hypothesis for polyene antibiotic activity, and the design of 3rd generation Erg-specific polyenes.

MK-5204 is a broad spectrum Candida antifungal agent derived from the natural product, enfumafungin. I was impressed that the molecule not only demonstrates oral efficacy but also has good oral PK in higher species (dog, cyno), given that the molecule is a large zwitterion with several very polar groups, including a primary amide, primary [...]

Infection with the malaria parasite, Plasmodium falciparum, is a leading cause of fatality in the tropical regions of the world, with >240M infections and >600K deaths each year, the majority of which are in sub-Saharan Africa. The need for new antimalarials is clear, given that over half of the world's population is at risk of infection, combined with the rise of resistance against current treatments. Novartis has played a key role in this fight and at the ACS Fall 2024 meeting in Denver, CO, they disclosed NVP-FVP954: a novel, fast-acting IV antimalarial for severe malaria.

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 [...]