期刊
DRUG DISCOVERY TODAY
卷 27, 期 6, 页码 1545-1553出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2022.02.024
关键词
Influenza virus; Cap-snatching mechanism; PB2 subunit; Drug discovery; Medicinal chemistry strategies
资金
- Zhe-jiang Provincial Natural Science Founda-tion of China [LD21H300001]
- Agricultural and Social Development Fund of Hang-zhou Science and Technology Committee [20201203B148]
This review summarizes the technologies and medicinal chemistry strategies for the development of PB2 inhibitors as a potential target for combating influenza virus, and provides insights for the fight against drug resistance.
Influenza is an acute respiratory infectious disease caused by influenza virus, leading to huge morbidity and mortality in humans worldwide. Despite the availability of antivirals in the clinic, the emergence of resistant strains calls for antivirals with novel mechanisms of action. The PB2 subunit of the influenza A virus polymerase is a promising target because of its vital role in the 'cap-snatching' mechanism. In this review, we summarize the technologies and medicinal chemistry strategies for hit identification, hit-to-lead and lead-to-candidate optimization, and current challenges in PB2 inhibitor development, as well as offering insights for the fight against drug resistance.
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