Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity.

During RNA replication, coronaviruses require proofreading to maintain the integrity of their large genomes. Nsp14 associates with viral polymerase complex to excise the mismatched nucleotides. Aside from the exonuclease activity, nsp14 methyltransferase domain mediates cap methylation, facilitating translation initiation and protecting viral RNA from recognition by the innate immune sensors.

The Tuberculosis Drug Accelerator at year 10: what have we learned?

The Tuberculosis Drug Accelerator, an experiment designed to facilitate collaboration in TB drug discovery by breaking down barriers among competing labs and institutions, has reached the 10-year landmark. We review the consortium’s achievements, advantages and limitations and advocate for application of similar models to other diseases.

Lessons learnt from assembling screening libraries for drug discovery for neglected diseases.

To enable the establishment of a drug discovery operation for neglected diseases, out of 2.3 million commercially available compounds 222 552 compounds were selected for an in silico library, 57 438 for a diverse general screening library, and 1 697 compounds for a focused kinase set. Compiling these libraries required a robust strategy for compound selection.