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Outline
Papain-like protease (PLpro or PLP) is a key non-structural protein in the replication process of coronaviruses. It is responsible for the cleavage and processing of viral polyproteins, and has deubiquitination and deISGylation activities, which can inhibit the host's innate immune response. Due to the high conservation of PLpro among various coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV, it has become an important target for the development of broad-spectrum coronavirus inhibitors. Since the outbreak of the COVID-19 pandemic, research on PLpro has advanced rapidly, and multiple classes of candidate molecules with clear structures and definite mechanisms have been identified, including non-covalent inhibitors (e.g., GRL0617 and its derivatives), covalent inhibitors (e.g., vinyl ester compounds), and inhibitors derived from natural products. This article reviews the research progress of PLpro-targeted inhibitors, covering their structural characteristics, activity data, mechanism of action, and discovery strategies, aiming to provide theoretical support and design ideas for the development of broad-spectrum anti-coronavirus drugs.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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