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Main Authors: Chi, Chen-Kung, Bajpai, Vertika, Li, Chen-Hung, Tsai, Hsin-Yi, Chen, Chien-Wen, Cheng, Chao-An, Liu, Hsia-Wei, Chang, Chi-Yao
Format: Artículo científico
Language:en
Published: Journal of fish diseases 2026
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Online Access:https://pubmed.ncbi.nlm.nih.gov/41524143/
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author Chi, Chen-Kung
Bajpai, Vertika
Li, Chen-Hung
Tsai, Hsin-Yi
Chen, Chien-Wen
Cheng, Chao-An
Liu, Hsia-Wei
Chang, Chi-Yao
author_facet Chi, Chen-Kung
Bajpai, Vertika
Li, Chen-Hung
Tsai, Hsin-Yi
Chen, Chien-Wen
Cheng, Chao-An
Liu, Hsia-Wei
Chang, Chi-Yao
Chi, Chen-Kung
Bajpai, Vertika
Li, Chen-Hung
Tsai, Hsin-Yi
Chen, Chien-Wen
Cheng, Chao-An
Liu, Hsia-Wei
Chang, Chi-Yao
collection PubMed - marine biology
contents Molnupiravir: A Prodrug of the Ribonucleoside β-D-N4-Hydroxycytidine Triphosphate Inhibits the Propagation of Nervous Necrosis Virus in Grouper Brain Cells. Chi, Chen-Kung Bajpai, Vertika Li, Chen-Hung Tsai, Hsin-Yi Chen, Chien-Wen Cheng, Chao-An Liu, Hsia-Wei Chang, Chi-Yao Animals Nodaviridae Antiviral Agents RNA Virus Infections Fish Diseases Brain Bass Virus Replication Molecular Docking Simulation Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis, otherwise known as viral encephalopathy and retinopathy in larval and juvenile marine fish worldwide. The pandemic outbreaks have caused nearly 100% mortality in hatcheries, leading to significant economic losses in the aquaculture industry. Since NNV attacks the insufficient immune competence fish at early developmental stages, there is an urgent need for effective antiviral drugs. Several nucleoside analogues, including Molnupiravir, have been developed to target viral RNA-dependent RNA polymerase (RdRp). This study examines the antiviral activity of Molnupiravir against NNV isolated from giant grouper (GG), Epinephelus lanceolatus (Bloch), using grouper brain (GB) cells as an infection model. The inhibition concentration for 50% of maximal effect (EC) of Molnupiravir on GGNNV propagation in GB cells was determined as 1.87 μM. Surprisingly, the titre of GGNNV reduced 50,000 at 100 μM of Molnupiravir treatment at 4-day post-infection, whereas treatment with 200 μM of Molnupiravir resulted in a 10 reduction in viral titre. The inhibition of viral replication and translation was further examined using RNA-fluorescence in situ hybridization (FISH) and immunocytochemistry detection, respectively. Moreover, administration of 100 μM Molnupiravir at early time 0 hpi resulted in a dramatic decrease in viral load, reducing cell-associated virus by approximately 4000-fold and released virus by 6000-fold. Finally, the molecular docking simulation model supports the interaction between NHC-TP and GGNNV RdRp for the successful therapeutics. These results demonstrated that Molnupiravir is a very effective therapeutic drug for controlling viral nervous necrosis caused by NNV infection.
format Artículo científico
id pubmed_41524143
institution PubMed
language en
publishDate 2026
publisher Journal of fish diseases
record_format pubmed
spellingShingle Molnupiravir: A Prodrug of the Ribonucleoside β-D-N4-Hydroxycytidine Triphosphate Inhibits the Propagation of Nervous Necrosis Virus in Grouper Brain Cells.
Chi, Chen-Kung
Bajpai, Vertika
Li, Chen-Hung
Tsai, Hsin-Yi
Chen, Chien-Wen
Cheng, Chao-An
Liu, Hsia-Wei
Chang, Chi-Yao
Animals
Nodaviridae
Antiviral Agents
RNA Virus Infections
Fish Diseases
Brain
Bass
Virus Replication
Molecular Docking Simulation
Molnupiravir: A Prodrug of the Ribonucleoside β-D-N4-Hydroxycytidine Triphosphate Inhibits the Propagation of Nervous Necrosis Virus in Grouper Brain Cells. Chi, Chen-Kung Bajpai, Vertika Li, Chen-Hung Tsai, Hsin-Yi Chen, Chien-Wen Cheng, Chao-An Liu, Hsia-Wei Chang, Chi-Yao Animals Nodaviridae Antiviral Agents RNA Virus Infections Fish Diseases Brain Bass Virus Replication Molecular Docking Simulation Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis, otherwise known as viral encephalopathy and retinopathy in larval and juvenile marine fish worldwide. The pandemic outbreaks have caused nearly 100% mortality in hatcheries, leading to significant economic losses in the aquaculture industry. Since NNV attacks the insufficient immune competence fish at early developmental stages, there is an urgent need for effective antiviral drugs. Several nucleoside analogues, including Molnupiravir, have been developed to target viral RNA-dependent RNA polymerase (RdRp). This study examines the antiviral activity of Molnupiravir against NNV isolated from giant grouper (GG), Epinephelus lanceolatus (Bloch), using grouper brain (GB) cells as an infection model. The inhibition concentration for 50% of maximal effect (EC) of Molnupiravir on GGNNV propagation in GB cells was determined as 1.87 μM. Surprisingly, the titre of GGNNV reduced 50,000 at 100 μM of Molnupiravir treatment at 4-day post-infection, whereas treatment with 200 μM of Molnupiravir resulted in a 10 reduction in viral titre. The inhibition of viral replication and translation was further examined using RNA-fluorescence in situ hybridization (FISH) and immunocytochemistry detection, respectively. Moreover, administration of 100 μM Molnupiravir at early time 0 hpi resulted in a dramatic decrease in viral load, reducing cell-associated virus by approximately 4000-fold and released virus by 6000-fold. Finally, the molecular docking simulation model supports the interaction between NHC-TP and GGNNV RdRp for the successful therapeutics. These results demonstrated that Molnupiravir is a very effective therapeutic drug for controlling viral nervous necrosis caused by NNV infection.
title Molnupiravir: A Prodrug of the Ribonucleoside β-D-N4-Hydroxycytidine Triphosphate Inhibits the Propagation of Nervous Necrosis Virus in Grouper Brain Cells.
topic Animals
Nodaviridae
Antiviral Agents
RNA Virus Infections
Fish Diseases
Brain
Bass
Virus Replication
Molecular Docking Simulation
url https://pubmed.ncbi.nlm.nih.gov/41524143/