Inhibition of RNA Helicases of ssRNA(+) Virus Belonging to Flaviviridae, Coronaviridae and Picornaviridae Families.
Inhibition of RNA Helicases of ssRNA(+) Virus Belonging to Flaviviridae, Coronaviridae and Picornaviridae Families.
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DOI：
10.1155/2011/213135
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发表时间：
2011
影响因子：
--
通讯作者：
Carta A
中科院分区：
文献类型：
--
作者：
Briguglio I;Piras S;Corona P;Carta A
许多病毒病原体编码被称为RNA解旋酶的运动蛋白，它在基因组复制中显示出各种功能。设计针对解旋酶治疗病毒感染的特异性和选择性药物的一般策略可以通过以下一种或多种机制起作用：通过干扰ATP结合从而限制解绕和易位所需的能量来抑制NTPase活性，或通过变构机制从而稳定酶在低解旋酶活性状态下的构象；核酸与解旋酶结合的抑制；抑制ATP水解偶联解绕；立体阻断解旋酶易位对解旋的抑制作用。最近，通过体外筛选研究，报道了几种苯并三唑、咪唑、咪唑二氮卓、吩噻嗪、喹啉、蒽环类、三苯甲烷、tropolone、吡咯、吖啶酮、小肽和香蕉素衍生物对黄病毒科、冠状病毒科和小核糖核酸病毒科病原体具有解旋酶抑制作用。
Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families.