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首页> 外文期刊>Protoplasma: An International Journal of Cell Biology >In silico analysis of drug-resistant mutant of neuraminidase (N294S) against oseltamivir
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In silico analysis of drug-resistant mutant of neuraminidase (N294S) against oseltamivir

机译：对奥司他韦抗药性神经氨酸酶（N294S）突变体的计算机分析

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摘要

The recent H1N1 influenza pandemic has attracted worldwide attention due to the high infection rate. Oseltamivir is a new class of anti-viral agent approved for the treatment and prevention of influenza infections. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infection. Until recently, only a low prevalence of neuraminidase inhibitor (NAI) resistance (<1 %) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a N294S neuraminidase mutation that was highly resistant to the NAI, oseltamivir. Hence, in the present study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular simulation approach. The docking analysis reveals that mutation (N294S) significantly affects the binding affinity of oseltamivir with mutant type NA. This is mainly due to the decrease in the flexibility of binding site residues and the difference in prevalence of hydrogen bonds in the wild and mutant structures. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.
机译：由于高感染率，最近的H1N1流感大流行引起了全世界的关注。 Oseltamivir是经过批准用于治疗和预防流感感染的新型抗病毒药。该药物的主要靶标是病毒表面糖蛋白神经氨酸酶（NA），它有助于新生病毒的释放，从而传播感染。直到最近，在循环病毒中仅检测到低的神经氨酸酶抑制剂（NAI）耐药率（<1％）。但是，有报告称，有大量的N（N1）S神经氨酸酶突变的A（H1N1）流感病毒株对NAI的奥司他韦具有高度耐药性。因此，在本研究中，我们通过分子模拟方法强调了点突变诱导的奥司他韦抗性在H1N1亚型神经氨酸酶中​​的作用。对接分析显示，突变（N294S）显着影响奥司他韦与NA型突变体的结合亲和力。这主要是由于结合位点残基的柔性降低以及野生和突变结构中氢键的普遍性差异所致。这项研究揭示了抗药性突变对生物系统中具有重要功能的大型集体运动的可能影响。

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