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Updated: Aug 26, 2025
Assays for the Specific Growth Rate and Cell-binding Ability of Rotavirus
Published on: January 28, 2019
Suppression of classical nuclear import pathway by importazole and ivermectin inhibits rotavirus replication
Rakesh Sarkar1, Shreya Banerjee1, Prolay Halder2
1Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, 700010, Kolkata, West Bengal, India.
Insights
Ivermectin and importazole show promise as new treatments for rotavirus, a common cause of infant gastroenteritis. These drugs target a key host factor, importin-β1, to inhibit viral replication and reduce disease severity in preclinical studies.
Area of Science:
- Virology
- Drug Discovery
- Gastroenterology
Background:
- Rotavirus is a leading cause of severe infant gastroenteritis globally.
- Current vaccines reduce rotavirus disease severity but not infection rates.
- Targeting host factors essential for viral replication offers a promising therapeutic strategy.
Purpose of the Study:
- To evaluate the therapeutic potential of ivermectin and importazole against rotaviruses.
- To investigate the mechanism of action of these compounds.
Main Methods:
- In vitro and in vivo assays were used to measure antirotaviral activity.
- Viral protein expression, viroplasm formation, and virus yield were quantified.
- The role of importin-β1 in rotavirus replication was assessed through knockdown experiments.
Main Results:
- Importin-β1 was identified as a critical host factor for rotavirus replication.
- Ivermectin and importazole reduced viral protein synthesis and infectious virus production in vitro.
- Both drugs inhibited importin-β1 function, demonstrating antirotaviral activity.
- In vivo studies in mice confirmed the efficacy of ivermectin and importazole at non-toxic doses, reducing viral shedding and intestinal damage.
Conclusions:
- Ivermectin and importazole exhibit significant antirotaviral potential.
- These compounds represent promising candidates for adjunct therapy against rotavirus infections.
Background:
Rotavirus is the foremost cause of acute gastroenteritis among infants in resource-poor countries, causing severe morbidity and mortality. The currently available rotavirus vaccines are effective in reducing severity of the disease but not the infection rates, thus antivirals as an adjunct therapy are needed to reduce the morbidity in children. Viruses rely on host cellular machinery for nearly every step of the replication cycle. Therefore, targeting host factors that are indispensable for virus replication could be a promising strategy.
Objectives:
To assess the therapeutic potential of ivermectin and importazole against rotaviruses.
Methods:
Antirotaviral activity of importazole and ivermectin was measured against various rotavirus strains (RV-SA11, RV-Wa, RV-A5-13, RV-EW) in vitro and in vivo by quantifying viral protein expression by western blot, analysing viroplasm formation by confocal microscopy, and measuring virus yield by plaque assay.
Results:
Importin-β1 and Ran were found to be induced during rotavirus infection. Knocking down importin-β1 severely impaired rotavirus replication, suggesting a critical role for importin-β1 in the rotavirus life cycle. In vitro studies revealed that treatment of ivermectin and importazole resulted in reduced synthesis of viral proteins, diminished production of infectious virus particles, and decrease in viroplasm-positive cells. Mechanistic study proved that both drugs perform antirotavirus activity by inhibiting the function of importin-β1. In vivo investigations in mice also confirmed the antirotavirus potential of importazole and ivermectin at non-toxic doses. Treatments of rotavirus-infected mice with either drug resulted in diminished shedding of viral particles in the stool sample, reduced expression of viral protein in the small intestine and restoration of damaged intestinal villi comapared to untreated infected mice.
Conclusions:
The study highlights the potential of importazole and ivermectin as antirotavirus therapeutics.
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