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Designing antimalarials that break into cells to lock down parasites [Biochemistry]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-06-29 , DOI: 10.1073/pnas.2108103118
Svetlana Glushakova, Joshua Zimmerberg

A once in a century new viral outbreak, COVID-19, has caused unfathomable numbers of deaths, toward 4 million. Yet an ancient disease, malaria, endemic to the residents of more than half of Earth, is even more devastating than this pandemic over time: It caused about 12 million deaths in the last 20 y alone, with estimates of tens of millions of deaths in the preceding three decades (1). Arguably the “most successful human pathogen,” the unicellular malaria parasites of the Plasmodium species are a medical and socioeconomic scourge in the zones of their transmission by female Anopheles mosquitoes, mostly sub-Saharan Africa, South Asia, and South America. Considering the number of people at risk to contract malaria, even a highly efficient vaccine would take years to roll out in these countries, during which time unvaccinated people would contract billions of new infections with millions of deaths. In addition, parasites escaping immune block in vaccinated people must be stopped by drug treatment shortly after initiation of the erythrocytic cycle of replication, the part of the parasite life cycle causing malaria, which is capable of killing people within 1 d to 2 d after appearance of symptoms. Continuous attempts at vaccine development are going on, now mostly to block parasites before they ever reach erythrocytes (2). The surge in deaths cited above can be traced to the development of parasite resistance to the affordable drug chloroquine (3). Artemisinin, a newer, powerful, and affordable antimalarial drug, seemed promising at first, but resistant strains now abound (4). Thus, the search for new antimalarial drugs will be a perpetual task until multitargeted drug mixtures are joined by vigorous antimosquito efforts and efficient, affordable, and heat-resistant vaccines identified by the World Health Organization to eliminate malaria. The impressive research reported by Lidumniece et al. (5), “Peptidic boronic …

中文翻译:

设计可进入细胞以锁定寄生虫的抗疟药 [生物化学]

百年一遇的新病毒爆发,COVID-19,已造成难以估量的死亡人数,接近 400 万人。然而,随着时间的推移,一种古老的疾病——疟疾——在地球上一半以上的居民中流行,其破坏性甚至比这次大流行病还要严重:仅在过去的 20 年里,它就造成了约 1200 万人死亡,估计有数千万人死亡。前三个十年(1)。可以说是“最成功的人类病原体”,疟原虫属的单细胞疟原虫是雌性按蚊传播区域的医学和社会经济祸害蚊子,主要是撒哈拉以南非洲、南亚和南美洲。考虑到有感染疟疾风险的人数,即使是高效疫苗也需要数年时间才能在这些国家推出,在此期间,未接种疫苗的人将感染数十亿新感染,数百万人死亡。此外,必须在红细胞复制周期开始后不久通过药物治疗来阻止已接种疫苗的寄生虫逃避免疫阻滞,这是寄生虫生命周期中引起疟疾的部分,可在出现后 1 至 2 天内杀死人的症状。疫苗开发的持续尝试正在进行中,现在主要是在寄生虫到达红细胞之前阻止它们(2)。上述死亡人数激增可以追溯到寄生虫对可负担得起的药物氯喹产生抗药性 ( 3 )。青蒿素是一种更新、强大且价格合理的抗疟药,起初似乎很有前景,但现在耐药菌株比比皆是 ( 4 )。因此,在多靶点药物混合物与世界卫生组织确定的用于消灭疟疾的有效灭蚊努力和高效、负担得起的耐热疫苗相结合之前,寻找新的抗疟疾药物将是一项永恒的任务。Lidumniece 等人报告的令人印象深刻的研究。( 5 ), “肽硼酸…
更新日期:2021-06-10
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