Nipah病毒基因组中两个保守的G-四链体形成基序的鉴定和表征及其与G-四链体特异性配体的相互作用。,Scientific Reports

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Nipah病毒基因组中两个保守的G-四链体形成基序的鉴定和表征及其与G-四链体特异性配体的相互作用。
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-30 , DOI: 10.1038/s41598-020-58406-8
Prativa Majee ₁ , Subodh Kumar Mishra ₁ , Nirali Pandya ₁ , Uma Shankar ₁ , Sanjeev Pasadi ₂ , K Muniyappa ₂ , Debasis Nayak ₁ , Amit Kumar ₁

Affiliation

G四联体（GQ）基元被认为是几种人类病原性病毒（如寨卡病毒，肝炎，埃博拉病毒和人类疱疹病毒）的潜在药物靶位。印度最近爆发的尼帕病毒（NiV）是一种致命性新兴的人畜共患病毒，由于目前尚无抗病毒药物或疫苗，对全球卫生安全构成潜在威胁。因此，在本研究中，我们试图评估NiV基因组中推定的G-四链体形成序列形成G-四链体结构并充当抗病毒化合物靶标的能力。各种生物物理和生化技术（例如NMR，CD，EMSA，DMS足迹测定法）支持的生物信息学分析证实，NiV的G和L基因中存在两个高度保守的G-四链体形成序列（HGQ）。这些基因分别编码细胞附着糖蛋白和RNA依赖性RNA聚合酶，对于病毒进入和在宿主细胞内复制至关重要。通过已知的G-四链体结合配体（如TMPyP4和Braco-19）稳定这些HGQ仍然是一种有前途的策略，可以抑制HGQ携带基因的表达，从而阻止病毒进入宿主细胞并在其中复制。因此，我们首次报道，尼帕病毒基因组中的HGQs是G-四链体特异性配体的靶标。因此，可以作为抗病毒治疗的潜在目标。通过已知的G-四链体结合配体（如TMPyP4和Braco-19）稳定这些HGQ仍然是一种有前途的策略，可以抑制HGQ携带基因的表达，从而阻止病毒进入宿主细胞并在其中复制。因此，我们首次报道，尼帕病毒基因组中的HGQs是G-四链体特异性配体的靶标。因此，可以作为抗病毒治疗的潜在目标。通过已知的G-四链体结合配体（如TMPyP4和Braco-19）稳定这些HGQ仍然是一种有前途的策略，可以抑制HGQ携带基因的表达，从而阻止病毒进入宿主细胞并在其中复制。因此，我们首次报道，尼帕病毒基因组中的HGQs是G-四链体特异性配体的靶标。因此，可以作为抗病毒治疗的潜在目标。

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Identification and characterization of two conserved G-quadruplex forming motifs in the Nipah virus genome and their interaction with G-quadruplex specific ligands.

The G-quadruplex (GQ) motifs are considered as potential drug-target sites for several human pathogenic viruses such as Zika, Hepatitis, Ebola, and Human Herpesviruses. The recent outbreaks of Nipah virus (NiV) in India, the highly fatal emerging zoonotic virus is a potential threat to global health security as no anti-viral drug or vaccine in currently available. Therefore, here in the present study, we sought to assess the ability of the putative G-quadruplex forming sequences in the NiV genome to form G-quadruplex structures and act as targets for anti-viral compounds. Bioinformatics analysis underpinned by various biophysical and biochemical techniques (such as NMR, CD, EMSA, DMS footprinting assay) confirmed the presence of two highly conserved G-quadruplex forming sequences (HGQs) in the G and L genes of NiV. These genes encode the cell attachment glycoprotein and RNA-dependent RNA polymerase, respectively and are essential for the virus entry and replication within the host cell. It remains possible that stabilization of these HGQs by the known G-quadruplex binding ligands like TMPyP4 and Braco-19 represents a promising strategy to inhibit the expression of the HGQ harboring genes and thereby stop the viral entry and replication inside the host cell. Accordingly, we report for the first time, that HGQs in Nipah virus genome are targets for G-quadruplex specific ligands; therefore, could serve as potential targets for anti-viral therapy.

更新日期：2020-01-31

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