甘油醛3-磷酸脱氢酶
溶酶体
自噬
内质网
登革热病毒
化学
生物化学
兰尼定受体
黄病毒
细胞生物学
脱氢酶
病毒
生物
酶
病毒学
细胞凋亡
作者
Kehui Zhang,Lihong Huang,Yefeng Cai,Yingying Zhong,Nanjun Chen,Fei Gao,Liang Zhang,Qi Li,Zhenming Liu,Rongxin Zhang,Liangren Zhang,Jianbo Yue
出处
期刊:FEBS Journal
[Wiley]
日期:2023-08-17
卷期号:290 (22): 5353-5372
被引量:1
摘要
We previously identified glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) as one of the cyclic adenosine diphosphoribose (cADPR)'s binding proteins and found that GAPDH participates in cADPR‐mediated Ca 2+ release from endoplasmic reticulum via ryanodine receptors (RyRs). Here, we aimed to chemically synthesise and pharmacologically characterise novel cADPR analogues. Based on the simulated cADPR–GAPDH complex structure, we performed the structure‐based drug screening, identified several small chemicals with high docking scores to cADPR's binding pocket in GAPDH and showed that two of these compounds, C244 and C346 , are potential cADPR antagonists. We further synthesised several analogues of C346 and found that its analogue, G42 , also mobilised Ca 2+ release from lysosomes. G42 alkalised lysosomal pH and inhibited autophagosome–lysosome fusion. Moreover, G42 markedly inhibited Zika virus (ZIKV, a flavivirus) or murine hepatitis virus (MHV, a β‐coronavirus) infections of host cells. These results suggest that G42 inhibits virus infection, likely by triggering lysosomal Ca 2+ mobilisation and inhibiting autophagy.
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