Borges Pedro Henrique Oliveira, Ferreira Sabrina Baptista, Silva Floriano Paes
Laboratory of Organic Synthesis and Biological Prospecting, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.
Laboratory of Experimental and Computational Biochemistry of Drugs, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, Brazil.
Viruses. 2024 Feb 27;16(3):366. doi: 10.3390/v16030366.
Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible for causing diseases in humans, like the West Nile virus (WNV) and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the mechanisms behind blocking viral protease's function is pivotal for the development of new antiviral drugs and therapeutical strategies. Apart from directly inhibiting the target protease, usually by targeting its active site, several new pathways have been explored to impair its activity, such as inducing protein aggregation, targeting allosteric sites or by inducing protein degradation by cellular proteasomes, which can be extremely valuable when considering the emerging drug-resistant strains. In this review, we aim to discuss the recent advances on a broad range of viral proteases inhibitors, therapies and molecular approaches for protein inactivation or degradation, giving an insight on different possible strategies against this important class of antiviral target.
病毒蛋白酶是药物开发的重要靶点，因为它们可以调节病毒复制、成熟、组装和细胞进入等关键途径。随着几种导致人类疾病的新病毒（如西尼罗河病毒（WNV）和最近的严重急性呼吸综合征冠状病毒2（SARS-CoV-2））的（重新）出现，了解阻断病毒蛋白酶功能背后的机制对于开发新的抗病毒药物和治疗策略至关重要。除了通常通过靶向其活性位点直接抑制目标蛋白酶外，还探索了几种新的途径来损害其活性，例如诱导蛋白质聚集、靶向变构位点或通过细胞蛋白酶体诱导蛋白质降解，在考虑新出现的耐药菌株时，这些途径可能极具价值。在这篇综述中，我们旨在讨论广泛的病毒蛋白酶抑制剂、治疗方法以及蛋白质失活或降解的分子方法的最新进展，深入了解针对这一重要抗病毒靶点的不同可能策略。
