Biology subjects

Nowell, C. J.

Publications and source records attributed to Nowell, C. J..

2 recordsLinked to original sources

bioRxiv2021

The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection

Summary ParagraphWe identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone1, a compound in clinical trials for anti-fibrotic and anti-inflammatory applications2, as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry3. We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone also potently suppresses SARS-CoV-2 replication post-entry and is 1,000-fold more potent than Remdesivir4. Inhibition of HS biosynthesis and SARS-CoV-2 infection depends on specific inhibition of PRS, possibly due to translational suppression of proline-rich proteins. We find that pp1a and pp1ab polyproteins of SARS-CoV-2, as well as several HS proteoglycans, are proline-rich, which may make them particularly vulnerable to halofuginones translational suppression. Halofuginone is orally bioavailable, has been evaluated in a phase I clinical trial in humans and distributes to SARS-CoV-2 target organs, including the lung, making it a near-term clinical trial candidate for the treatment of COVID-19.

microbiology↗

bioRxiv2021

Regulation of oogenesis in the queen honey bee (Apis mellifera)

In the honey bee (Apis mellifera), queen and worker castes originate from identical genetic templates but develop into different phenotypes. Queens lay up to 2,000 eggs daily whereas workers are sterile in the queens presence. Periodically queens stop laying; during swarming, when resources are scarce in winter and when they are confined to a cage by beekeepers. We used confocal microscopy and gene expression assays to investigate the control of oogenesis in honey bee queen ovaries. We show that queens use different combination of checkpoints to regulate oogenesis compared to honey bee workers and other insect species. However, both queen and worker castes use the same programmed cell death pathways to terminate oocyte development at their caste-specific checkpoints. Our results also suggest that the termination of oogenesis in queens is driven by nutritional stress. Thus, queens may regulate oogenesis via the same regulatory pathways that were utilised by ancestral solitary species but have adjusted physiological checkpoints to suit their highly-derived life history. Summary statementHoney bee queens regulate oogenesis using a different combination of checkpoints to workers, but both castes use the same molecular pathways.

developmental biology↗