Discovery of Non-Covalent Inhibitors for SARS-CoV-2 PLpro: Integrating Virtual Screening, Synthesis, and Experimental Validation.

The SARS-CoV-2 pandemic has significantly challenged global public health, highlighting the need for effective therapeutic options. This study focuses on the papain-like protease (PLpro) of SARS-CoV-2, which is a critical enzyme for viral polyprotein processing, maturation, and immune evasion. We employed a combined approach that began with computational models in a virtual screening campaign, prioritizing compounds from our in-house chemical library against PLpro.

Attempted synthesis of a -metalated calix[4]arene.

An evidence for the formation of a rare -metalated inherently chiral calix[4]arene is described. Our strategy involved using a mesoionic carbene to direct C-H activation, but proved to form an unexpectedly unstable intermediate that was identified through high-resolution mass spectrometry. On route to our target, a new optimized method to mononitrocalix[4]arenes was developed, including optimized and high yielding transformations to azide and 1,2,3-triazole derivatives which may have application in other areas of research.