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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
Ursolic acid: A novel antiviral compound inhibiting rotavirus infection in vitro
M J Tohmé1, M C Giménez2, A Peralta3
1IHEM, Universidad Nacional de Cuyo, CONICET, Facultad de Ciencias Médicas, Mendoza, Argentina; Facultad de Farmacia y Bioquímica, Universidad Juan Agustín Maza, Mendoza, Argentina.
Insights
Ursolic acid shows promise as a new rotavirus treatment. This compound effectively inhibits rotavirus replication and maturation in cell cultures without significant toxicity, suggesting potential therapeutic applications.
Area of Science:
- Virology
- Natural Product Chemistry
- Drug Discovery
Background:
- Rotavirus is a primary cause of severe gastroenteritis in young children, particularly in developing nations.
- Current treatments for rotavirus are limited, highlighting the urgent need for effective antiviral therapies.
- Ursolic acid, a naturally occurring triterpenoid, possesses known antiviral properties.
Purpose of the Study:
- To investigate the potential of ursolic acid as an antirotaviral agent.
- To assess the virucidal and cytotoxic effects of ursolic acid.
- To evaluate the impact of ursolic acid on rotavirus replication and maturation in vitro.
Main Methods:
- Analysis of ursolic acid's virucidal effect on rotavirus particles.
- Assessment of ursolic acid's cytotoxicity on cultured cells.
- In vitro evaluation of ursolic acid's efficacy against rotavirus infection, including viral titre, protein levels, and viroplasm formation.
Main Results:
- Ursolic acid demonstrated no virucidal effect at concentrations up to 40 µM.
- Cytotoxicity was observed starting at 20 µM ursolic acid.
- At 10 µM, ursolic acid significantly inhibited rotavirus replication, reduced viral titre, affected viral protein levels (VP6, NSP2), and disrupted viral particle maturation and viroplasm formation.
Conclusions:
- Ursolic acid exhibits significant in vitro antiviral activity against rotavirus.
- The compound interferes with early and late stages of the rotavirus replication cycle.
- Ursolic acid represents a potential candidate for developing novel therapeutic strategies against rotavirus infections.
Abstract:
Rotavirus is one of the leading causes of severe acute gastroenteritis in children under 5 years of age, mainly affecting developing countries. Once the disease is acquired, no specific treatment is available; as such, the development of new drugs for effective antirotaviral treatment is critical. Ursolic acid is a pentacyclic triterpenoid with antiviral activity, which has been studied extensively in vitro and in vivo. To study the potential antirotaviral activity of ursolic acid, its toxic potential for viral particles (virucidal effect) and cultured cells (cytotoxicity) was analysed. No effect on virion infectivity was observed with treatments of up to 40 µM ursolic acid, while incipient cytotoxicity started to be evident with 20 µM ursolic acid. The antiviral potential of ursolic acid was evaluated in in-vitro rotavirus infections, demonstrating that 10 µM ursolic acid inhibits rotavirus replication (observed by a decrease in viral titre and the level of the main viral proteins) and affects viral particle maturation (a process associated with the endoplasmic reticulum) 15 h post infection. Interestingly, ursolic acid was also found to hamper the early stages of the viral replication cycle, as a significant reduction in the number and size of viroplasms, consistent with a decrease in VP6 and NSP2 viral proteins, was observed 4 h post infection. As such, these observations demonstrate that ursolic acid exhibits antiviral activity, suggesting that this chemical could be used as a new treatment for rotavirus.
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