The pace and efficiency of drug target strategies have been emanating debates among researchers in the field of drug development. Covalent inhibitors possess significant advantages over non-covalent inhibitors, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors. However, toxicity can be a real challenge related to this class of therapeutics. From the challenges of irreversible drug toxicity to the declining reactivity of reversible drugs, herein we provide justifications from the computational point of view. It was evident that both classes had its merits; however, with the increase in drug resistance, covalent inhibition seemed more suitable. There also seems to be enhanced selectivity of the covalent systems, proving its use as a therapeutic regimen worldwide. We believe that this study will assist researchers in making informed decisions on which drug class to choose as lead compounds in the drug discovery pipeline.

中文翻译：

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共价与非共价酶抑制：我们应该采取哪种途径？从分子模型的角度论证好与坏的合理性。

药物靶标策略的步伐和效率一直引起药物开发领域研究人员的争论。共价抑制剂与非共价抑制剂相比具有显着优势，因此共价弹头可以靶向特定靶蛋白的稀有残基，从而导致了高选择性抑制剂的发展。但是，毒性可能是与此类疗法有关的真正挑战。从不可逆药物毒性到可逆药物反应性下降的挑战，本文从计算的角度提供了依据。显然，这两个阶级都有其优点。然而，随着耐药性的增加，共价抑制似乎更合适。共价体系的选择性似乎也有所提高，证明其在世界范围内作为治疗方案的用途。我们相信这项研究将帮助研究人员做出明智的决定，以决定在药物发现管道中选择哪种药物作为先导化合物。