The current strategies of optimization of oseltamivir against mutant neuraminidases of influenza A:A review
The current strategies of optimization of oseltamivir against mutant neuraminidases of influenza A:A review
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DOI：
10.1016/j.ejmech.2022.114711
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yongshou Tian
中科院分区：
文献类型：
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作者：
Kuanglei Wang;Huicong Zhang;Yongshou Tian
Influenza with a tendency to cause pandemic and epidemic is an infectious disease with a high of morbidity and mortality. Neuraminidase (NA) inhibitors are proved to prevent and treat influenza. Among the four Neuraminidase inhibitors (NAIs) licensed, oseltamivir is most commonly used. With the extensive usage, several variants containing mutant NAs especially H274Y point mutation exhibit reduced susceptibility. In this review, we covered the current drugs available for influenza, the analysis of active site of NA, the mutant types of NAs and the molecular mechanism of drug resistance brought by H274Y mutant NAs. For recovering the susceptibility to oseltamivir, many series of oseltamivir analogues were designed. We present the details of the strategies of strengthening the interactions with S2 via introducing strong basic fragment, targeting additional subpockets and making full use of Zone X by modifying 3-pentyl of OC. PROTAC targeting NA and combination therapies are also introduced. Further, the advantages and disadvantages of these methods are also discussed.
