Aldehydes can react with amine and alcohol nucleophiles and thus with lysine, serine, and threonine residues, with N-terminal amines, and with N-terminal serine, threonine, and cysteine residues. A variety of aldehydes have been used as covalent inhibitors. For example, the US FDA-approved pharmaceutical voxelator (a treatment for sickle-cell disease) (Supplementary table ) reacts at the N-terminus of the β-chain of hemoglobin to form an imine; the covalently modified hemoglobin forms complexes with enhanced oxygen affinity. Roblitinib (Supplementary table ) was developed as an FGFR4 inhibitor using an aldehyde as a warhead. A variety of antiviral compounds have been developed as inhibitors for the main protease M pro of SARS-CoV-2 for treatment or prevention of COVID-19 infection using an aldehyde moiety (or protected aldehyde moieties such as α-hydroxysulfinates) and bind to a cysteine residue in the active site. Nitriles are compounds possessing a carbon-nitrogen triple bond (R-CN). The triple bond renders the nitrile group linear and relatively unhindered, making it more easily available for reactions with nucleophiles. The terminal lone pair on the nitrogen atom makes nitriles potentially reactive with electrophiles, but the product is likely to have enhanced reactivity towards nucleophiles. The carbon atom of nitriles is electrophilic, both because of the hybridization of the carbon atom (the increased s character in bonds to the carbon make the carbon atom effectively more electronegative) and because carbon is less electronegative than nitrogen. Nitriles act as less hindered and more electron-deficient analogs of carbonyl compounds. Nucleophiles add to the carbon atom to form substituted imines (after protonation); the presence of a lone pair on the nitrogen atom renders addition reactions of heteroatomic (nitrogen, oxygen, and sulfur) nucleophiles reversible.