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  3. G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy

G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy

  • PLoS Pathog. 2023 Dec 7;19(12):e1011796. doi: 10.1371/journal.ppat.1011796.
Congbao Xie 1 2 3 4 5,  Xianpeng Zhang 1 2 6,  Wenyue Pei 2 7,  Ju Sun 1 2 3 4 5,  Hongqi Shang 1 2,  Zhiyuan Huang 8,  Mengxi Wang 6,  Daozhong Wang 1 2 3 4 5,  Guiqian Wang 8,  Zhikun Gui 9,  Sisi Liu 9,  Feng Li 2 7,  Dengguo Wei 1 2 3 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 2 Hubei Hongshan Laboratory, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, China.
  • 3 National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, China.
  • 4 Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan, China.
  • 5 Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
  • 6 College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 7 National Key Laboratory for Germplasm Innovation and Utilization of Horticultural Crops, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 8 College of Informatics, Huazhong Agricultural University, Wuhan, China.
  • 9 College of Chemistry, Huazhong Agricultural University, Wuhan, Hubei, China.
PMID: 38060599 DOI: 10.1371/journal.ppat.1011796
Abstract

Plant viruses seriously disrupt crop growth and development, and classic protein-targeted Antiviral drugs could not provide complete protection against them. It is urgent to develop Antiviral compounds with novel targets. Photodynamic therapy shows potential in controlling agricultural pests, but nonselective damage from Reactive Oxygen Species (ROS) unexpectedly affects healthy tissues. A G-quadruplex (G4)-forming sequence in the tobacco mosaic virus (TMV) genome was identified to interfere the RNA replication in vitro, and affect the proliferation of TMV in tobacco. N-methyl mesoporphyrin IX stabilizing the G4 structure exhibited inhibition against viral proliferation, which was comparable to the inhibition effect of ribavirin. This indicated that G4 could work as an Antiviral target. The large conjugate planes shared by G4 ligands and photosensitizers (PSs) remind us that the PSs could work as Antiviral agents by targeting G4 in the genome of TMV. Chlorin e6 (Ce6) was identified to stabilize the G4 structure in the dark and selectively cleave the G4 sequence by producing ROS upon LED-light irradiation, leading to 92.2% inhibition against TMV in vivo, which is higher than that of commercial ningnanmycin. The inhibition of Ce6 was lost against the mutant variants lacking the G4-forming sequence. These findings indicated that the G-quadruplex in the TMV genome worked as an important structural element regulating viral proliferation, and could act as the Antiviral target of photodynamic therapy.

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