Introduction Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the devastating pandemic named coronavirus disease 2019 (COVID-19). Unfortunately, the discovery of antiviral agents to combat COVID-19 is still an unmet need. Transmembrane serine protease 2 (TMPRSS2) is an important mediator in viral infection and thus, TMPRRS2 inhibitors may be attractive agents for COVID-19 treatment. Areas covered This review article discusses the role of TMPRSS2 in SARS-CoV-2 cell entry and summarizes the inhibitors of TMPRSS2 and their potential anti-SARS activity. Two known TMPRSS2 inhibitors, namely camostat and nafamostat, approved drugs for the treatment of pancreatitis, are under clinical trials as potential drugs against COVID-19. Expert opinion Due to the lack of the crystal structure of TMPRSS2, homology models have been developed to study the interactions of known inhibitors, including repurposed drugs, with the enzyme. However, novel TMPRSS2 inhibitors have been identified through high-throughput screening, and appropriate assays studying their in vitro activity have been set up. The discovery of TMPRSS2ʹs crystal structure will facilitate the rational design of novel inhibitors and in vivo studies and clinical trials will give a clear answer if TMPRSS2 inhibitors could be a new weapon against COVID-19.

Fatty-acid-based nitroalkenes have recently received great attention because of their bioactivities. On the contrary, peptide- or amino-acid-based nitroalkenes have been scarcely explored so far, although they may exhibit interesting biological properties, for example, as enzyme inhibitors. In this work, we study protocols for the efficient synthesis of nitroalkenes based on natural amino acids. A variety of N-protected amino alcohols and Weinreb amides, derived from α-amino acids, were converted to the corresponding N-protected amino aldehydes, and, through a Henry reaction with nitroalkanes, produced the corresponding nitro alcohols. The subsequent elimination reaction led to the (E)-isomer of amino-acid-based nitroalkenes in moderate to high yields.