Research funded by the National Institutes of Health (NIH) generated $2.46 in economic activity for every $1 of funding in 2023, a total of $92.9 billion, according to an

Small-molecule ligands have been developed that covalently attach to their cognate RNA aptamers in vitro and in living cells. This strategy opens up new avenues for RNA imaging applications (for examp...

Crimean-Congo hemorrhagic fever virus is a widespread tickborne virus that infects humans. Engineering-based structural studies of the viral glycoprotein complexes GP38-Gn and GP38-Gn-Gc provide insights to their function in the viral life cycle. GP38-Gn-Gc confers partial protection against lethal viral challenge in mice, showing promise as a vaccine antigen for further development.

Ebola and Marburg (EBOV and MARV) filoviral infections lead to fatal hemorrhagic fevers and have caused over 30 outbreaks in the last 50 years. Currently, there are no FDA-approved small molecule therapeutics for effectively treating filoviral diseases. To address this unmet medical need, we have conducted a systematic structural optimization of an early lead compound, N-(4-(4-methylpiperidin-1-yl)-3-(trifluoromethyl)phenyl)-4-(morpholinomethyl)benzamide (1), borne from our previously reported hit-to-lead effort. This secondary round of structure–activity relationship (SAR) involved the design and synthesis of several deconstructed and reconstructed analogs of compound 1, which were then tested against pseudotyped EBOV and MARV. The antiviral activities of the most promising leads were further validated in infectious assays. The optimized analogs exhibited desirable antiviral activity against different ebolaviruses and reduced off-target activity. Additionally, they also possessed druglike properties, that make them ideal candidates for in vivo efficacy studies as part of our ongoing drug discovery campaign against EBOV and MARV.

The docking of a 1.7 billion- versus a 99 million-molecule virtual library against β-lactamase revealed that the larger-sized library produced improved hit rates and potency along with an increased nu...

Many human proteins lack chemical probes and are even considered undruggable. Ogasawara et al. describe diversity-oriented synthesis-inspired photoreactive small molecules (photo-stereoprobes) and the...