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Two pairs of dibenzospiroketal racemates, (±)-epicospirocin A (1a/1b), (±)-1-epi-epicospirocin A (2a/2b), two (+)-enantiomers of aspermicrones, ent-aspermicrone B (3b) and ent-aspermicrone C (4b), together with two hemiacetal epimeric mixtures, epicospirocin B/1-epi-epicospirocin...

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Since the Coronavirus Disease 2019 (COVID‐19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much‐shortened timeline of 3–6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS‐CoV‐2‐neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization  approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late‐stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next‐generation sequencing‐based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID‐19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic‐related biologics development may innovate typical biologics development timelines and become a new standard in the industry.

Microbes serve as the most important resource for drug discovery. During our screening for bioactive compounds from our natural products library, a pathogenic fungus, Microdochium majus strain 99049, from wheat was selected for further investigation. A new alkaloid named brocaeloid D (1), together with six previously characterized compounds (2–7) were identified. Compound 1 belongs to 4-oxoquinoline with C-2 reversed prenylation and a succinimide substructure. All the structures of these newly isolated compounds were determined by different means in spectroscopic experiments. The absolute configurations of 1 was further deduced from comparison of its CD spectrum with that of known compound 2. The bioactivities of these identified compounds were evaluated against several pathogenic microorganisms and cancer cell lines. Compounds 1–5 showed activity against HUH-7 human hepatoma cells with IC50 values of 80 μg/mL. Compound 6 showed mild activity against HeLa cells (IC50 = 51.9 μg/mL), weak anti-MTB activity (MIC = 80  μg/mL), and moderate anti-MRSA activity (MIC = 25 μg/mL), and compound 7 showed weak anti-MRSA activity (MIC = 100 μg/mL).