来自HIV-1病毒整合酶基因序列多样性水平的评估,支持伊维菌素与整合酶输入复合物在SARS-COV-2感染中缺乏目标特异性

Pierre Teodosio Felix
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摘要

在世界各地的测试中,新药物疗法作为潜在的sars-cov-2病毒复制抑制剂已经出现。最近,其中一种药物伊维菌素被报道为体外HIV-1蛋白核输入抑制剂,很快成为一项国际勘探工作的目标(尚未发表),并对患者进行了COVID-19检测。然而,了解复杂药物核输入中涉及的生物成分的进化方面有助于理解这些关系如何存在于病毒感染的失活中。因此,我们分析了HIV-1整合酶基因的153个序列,分析了它们的遗传结构和分子多样性,发现该基因存在两个不同的群体,而且不仅检测到一个群体,而且每个群体的结构程度不同。这些结果支持了HIV-1基因缺乏保守性的解释,以及现有多态性的数量,仅针对这种复合物的结构,意味着药物在群体水平上无效。因此,在HIV-1中发现的分子多样性可以推断到其他病毒,如包括SARS-CoV-2,并且药物与整合酶输入蛋白复合物相互作用的功能可以进一步降低。
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Evaluation of Diversity Levels of the Integrase Gene Sequences Coming from HIV-1 Virus, Supporting the Lack of Target Specificity of Ivermectin vs. the Integrase-Importin Complex in SARS-COV-2 Infection
Therapies with new drugs have been appearing in tests worldwide as potential inhibitors of sars-cov-2 virus replication. Recently, one of these drugs, Ivermectin, was reported as an inhibitor of the nuclear import of HIV-1 proteins in vitro, soon becoming the target of an international prospecting work (not yet published), with patients tested for COVID-19. However, understanding the evolutionary aspects of the biological components involved in the complex drug-nuclear import helps in understanding how these relationships exist in the deactivation of viral infections. Thus, 153 sequences of the HIV-1 integrase gene were analyzed for their genetic structure and molecular diversity and the presence of two distinct groups for the Gene and not only one was detected as well as different degrees of structuring for each of these groups. These results support the interpretation of the lack of conservation of the HIV-1 gene and that the number of existing polymorphisms, only for this structure of the complex, implies the non-efficiency of a drug at population levels. Thus, the molecular diversity found in HIV-1 can be extrapolated to other viruses, such as Including, SARS-CoV-2 and the functionality of the drug, interacting with the integrase-importin complex, can be further decreased.
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