URSOLIC ACID: A NOVEL ANTIVIRAL COMPOUND INHIBITING ROTAVIRUS INFECTION IN VITRO.
Int J Antimicrob Agents. 2019 Jul 26. Epub 2019 Jul 26. PMID: 31356859
M J Tohmé
Rotavirus is one of the leading causes of severe acute gastroenteritis in children under five years of age, mainly affecting developing countries. Once the disease is acquired, no specific treatment is available; thus the development of new pharmacological drugs for effective anti-Rotaviral therapies becomes critical. Ursolic acid is a pentacyclic triterpenoid which antiviral activity has been extensively studied in vitro and in vivo. To study the potential anti-Rotaviral activity of ursolic acid, we first analyzed its toxic potential over both, the viral particles (virucidal effect) and the cultured cells (cytotoxicity). We observed no virion infectivity affectation with treatments of up to 40µM ursolic acid, while incipient cytotoxicity started to be evident with 20 µM ursolic acid. Next, we evaluated the antiviral potential of ursolic acid in in vitro Rotavirus infections, demonstrating that 10 µM ursolic acid inhibits Rotavirus replication, observed by a decrease in the viral titerand the level of the main viral proteins and an impact of ursolic acid on viral particles maturation, a process associated to the endoplasmic reticulum 15 h post infection. Interestingly, we determined that ursolic acid also hampers the early stages of the viral replication cycle, since a significant reduction in the number and size of viroplasms, consistent with a decrease in VP6 and NSP2 viral proteins was observed after 4 h of infection. Thus, our observations demonstrate that ursolic acid exhibits antiviral activity suggesting that this chemical could be potentially used as a new anti-Rotavirus therapeutic compound.