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

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

  • Cell Discov. 2022 Sep 6;8(1):86. doi: 10.1038/s41421-022-00450-x.
Geng Qin # 1 2,  Chuanqi Zhao # 1 2,  Yan Liu # 3,  Cheng Zhang # 3 4,  Guang Yang 3,  Jie Yang 1 2,  Zhao Wang 1 2,  Chunyu Wang 5,  Changchun Tu 3,  Zhendong Guo 3,  Jinsong Ren 1 2,  Xiaogang Qu 6 7
Affiliations

Affiliations

  • 1 Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
  • 2 University of Science and Technology of China, Hefei, Anhui, China.
  • 3 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China.
  • 4 Hebei Agricultural University, College of Veterinary Medicine, 2596 Lucky South Street, Baoding, Hebei, China.
  • 5 State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin, China.
  • 6 Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China. xqu@ciac.ac.cn.
  • 7 University of Science and Technology of China, Hefei, Anhui, China. xqu@ciac.ac.cn.
  • # Contributed equally.
PMID: 36068208 DOI: 10.1038/s41421-022-00450-x
Abstract

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-(N-methyl-4-pyridyl)porphine (TMPyP4) targeting SARS-CoV-2 G4s shows excellent Antiviral activity, while its N-methyl-2-pyridyl 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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