中文摘要：

小分子共价抑制剂，也称不可逆抑制剂，是通过共价键与靶标发生不可逆结合而发挥其生物学功能的一类抑制剂。与非共价抑制剂相比，虽然共价抑制剂在生物活性方面具有较大的优势，但如果这类抑制剂脱靶，也将带来更大的毒副作用。由于共价抑制剂的这种两面性，长期以来药物研发人员对其是敬而远之。近年来，由于可逆抑制剂所面临的难以解决的耐药性等问题，人们又重新重视对共价抑制剂的研发。本文将对近年来共价抑制剂的研究进展，以及共价抑制剂与靶蛋白残基的作用模式进行综述。

英文摘要：

Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This ＂double-edged swords＂ property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.