Abstract
Abstract BACKGROUND Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens. The modification of nucleosides is an effective method to develop anti‐TMV agents. A series of novel cytidine derivatives were designed and synthesized, and their antiviral activities against TMV were evaluated systematically. RESULTS Activity assays revealed that 5z exhibited excellent protective and curative effects, with a half‐effective concentration (EC 50 ) of 191.84 μg mL −1 , outperforming the control commercial agents ningnanmycin (240.79 μg mL −1 ) and ribavirin (622.22 μg mL −1 ). The mode of action (MoA) of 5z was thoroughly investigated through a multifaceted approach involving TMV‐GFP agrobacterium infiltration inoculation, chlorophyll content measurement, defense enzyme activity analysis and molecular docking. Mechanistic studies revealed that 5z exerts its multi‐target antiviral effects by specifically binding to the TMV coat protein (TMV‐CP), while simultaneously triggering the plant's defense enzyme system and boosting photosynthetic efficiency. CONCLUSION Structure–activity relationships (SARs) were established for the cytidine derivatives, providing guidance for the design of cytidine‐based antiviral agents. Given its potent antiviral activity and unique mechanism of action, 5z shows strong promise as a novel antiviral agent. © 2026 Society of Chemical Industry.
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Claims 9
Claim · model-written summary
Compound 5z exhibited excellent protective and curative effects against TMV.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Treatment
- 5ze3
- Outcome
- protective and curative effectse3
- Direction
- excellente3
Not reportedComparator
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e3“5z exhibited excellent protective and curative effects”
Claim · model-written summary
Compound 5z had an EC50 of 191.84 μg mL −1 against TMV.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Outcome
- EC 50e5
- Value
- 191.84 μg mL −1e5
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e5“(EC 50 ) of 191.84 μg mL −1”
Claim · model-written summary
Compound 5z outperformed the commercial agent ningnanmycin in EC50.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Treatment
- 5ze3
- Outcome
- EC 50e5
- Direction
- outperforminge2
- Qualifier
- 240.79 μg mL −1e2
- Comparator
- ningnanmycine2
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e2“outperforming the control commercial agents ningnanmycin (240.79 μg mL −1 ) and ribavirin (622.22 μg mL −1 )”
e5“(EC 50 ) of 191.84 μg mL −1”
e3“5z exhibited excellent protective and curative effects”
Claim · model-written summary
Compound 5z outperformed the commercial agent ribavirin in EC50.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Treatment
- 5ze3
- Outcome
- EC 50e5
- Direction
- outperforminge2
- Qualifier
- 622.22 μg mL −1e2
- Comparator
- ribavirine2
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e2“outperforming the control commercial agents ningnanmycin (240.79 μg mL −1 ) and ribavirin (622.22 μg mL −1 )”
e5“(EC 50 ) of 191.84 μg mL −1”
e3“5z exhibited excellent protective and curative effects”
Claim · model-written summary
Compound 5z exerts antiviral effects by specifically binding the TMV coat protein.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Gene
- TMV coat proteine6
- Outcome
- antiviral effectse6
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e6“5z exerts its multi‐target antiviral effects by specifically binding to the TMV coat protein”
Claim · model-written summary
Compound 5z triggered the plant defense enzyme system.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Treatment
- 5ze3
- Outcome
- defense enzyme systeme7
- Direction
- triggeringe7
Not reportedComparator
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e3“5z exhibited excellent protective and curative effects”
e7“simultaneously triggering the plant's defense enzyme system and boosting photosynthetic efficiency”
Claim · model-written summary
Compound 5z boosted photosynthetic efficiency.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Treatment
- 5ze3
- Outcome
- photosynthetic efficiencye7
- Direction
- boostinge7
Not reportedComparator
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e3“5z exhibited excellent protective and curative effects”
e7“simultaneously triggering the plant's defense enzyme system and boosting photosynthetic efficiency”
Claim · model-written summary
The authors conclude that compound 5z shows strong promise as a novel antiviral agent.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Outcome
- novel antiviral agente1
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e1“5z shows strong promise as a novel antiviral agent”
Claim · model-written summary
Structure-activity relationships were established for the cytidine derivatives.
- Taxon
- Tobacco mosaic virus
Tobacco mosaic viruse0 - Outcome
- relationships (SARs)e1
Organisms pictured · Representative pictures of the matched species, not figures from the paper.

Verbatim
e0“Tobacco mosaic virus (TMV) is one of the most destructive plant pathogens”
e1“relationships (SARs) were established for the cytidine derivatives”