RNA G-quadruplex formed in SARS-CoV-2 used for COVID-19 treatment in animal models

文献类型： 外文期刊

第一作者： Qin, Geng

作者： Qin, Geng;Zhao, Chuanqi;Yang, Jie;Wang, Zhao;Ren, Jinsong;Qu, Xiaogang;Qin, Geng;Zhao, Chuanqi;Yang, Jie;Wang, Zhao;Ren, Jinsong;Qu, Xiaogang;Qin, Geng;Zhao, Chuanqi;Yang, Jie;Wang, Zhao;Ren, Jinsong;Qu, Xiaogang;Liu, Yan;Zhang, Cheng;Yang, Guang;Tu, Changchun;Guo, Zhendong;Zhang, Cheng;Wang, Chunyu

作者机构：

期刊名称：CELL DISCOVERY （ 影响因子：38.079； 五年影响因子：19.649 ）

ISSN：

年卷期： 2022 年 8 卷 1 期

页码：

收录情况： SCI

摘要： The ongoing COVID-19 pandemic has continued to affect millions of lives worldwide, leading to the urgent need for novel therapeutic strategies. G-quadruplexes (G4s) have been demonstrated to regulate life cycle of multiple viruses. Here, we identify several highly conservative and stable G4s in SARS-CoV-2 and clarify their dual-function of inhibition of the viral replication and translation processes. Furthermore, the cationic porphyrin compound 5,10,15,20-tetrakis-(Nmethyl-4-pyridyl)porphine (TMPyP4) targeting SARS-CoV-2 G4s shows excellent antiviral activity, while its N-methyl-2pyridyl positional isomer TMPyP2 with low affinity for G4 has no effects on SARS-CoV-2 infection, suggesting that the antiviral activity of TMPyP4 attributes to targeting SARS-CoV-2 G4s. In the Syrian hamster and transgenic mouse models of SARS-CoV-2 infection, administration of TMPyP4 at nontoxic doses significantly suppresses SARS-CoV-2 infection, resulting in reduced viral loads and lung lesions. Worth to note, the anti-COVID-19 activity of TMPyP4 is more potent than remdesivir evidenced by both in vitro and in vivo studies. Our findings highlight SARS-CoV-2 G4s as a novel druggable target and the compelling potential of TMPyP4 for COVID-19 therapy. Different from the existing anti-SARS-CoV-2 therapeutic strategies, our work provides another alternative therapeutic tactic for SARS-CoV-2 infection focusing on targeting the secondary structures within SARS-CoV-2 genome, and would open a new avenue for design and synthesis of drug candidates with high selectivity toward the new targets.

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