Quercetin, a flavonoid, combats rotavirus infection by deactivating rotavirus-induced pro-survival NF-κB pathway

Shreya Banerjee; Rakesh Sarkar; Arpita Mukherjee; Shin-Ichi Miyoshi; Kei Kitahara; Prolay Halder; Hemanta Koley; Mamta Chawla-Sarkar

doi:10.3389/fmicb.2022.951716

Quercetin, a flavonoid, combats rotavirus infection by deactivating rotavirus-induced pro-survival NF-κB pathway

Front Microbiol. 2022 Aug 2:13:951716. doi: 10.3389/fmicb.2022.951716. eCollection 2022.

Authors

Shreya Banerjee¹, Rakesh Sarkar¹, Arpita Mukherjee¹, Shin-Ichi Miyoshi², Kei Kitahara³, Prolay Halder⁴, Hemanta Koley⁴, Mamta Chawla-Sarkar¹

Affiliations

¹ Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
² Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
³ Collaborative Research Center of Okayama University for Infectious Diseases in India, Okayama University, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
⁴ Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.

Abstract

Rotavirus (RV) is the leading cause of acute gastroenteritis and watery diarrhea in children under 5 years accounting for high morbidity and mortality in countries with poor socioeconomic status. Although vaccination against RV has been implemented in more than 100 countries, the efficacy of vaccine has been challenged in low-income settings. The lack of any FDA-approved drug against RV is an additional concern regarding the treatment associated with rotavirus-induced infantile death. With the purpose for the discovery of anti-RV therapeutics, we assessed anti-rotaviral potential of quercetin, a well-characterized antioxidant flavonoid. In vitro study revealed that quercetin treatment resulted in diminished production of RV-SA11 (simian strain) viral particles in a concentration-dependent manner as estimated by the plaque assay. Consistent with this result, Western blot analysis also revealed reduced synthesis of viral protein in quercetin-treated RV-SA11-infected MA104 cells compared to vehicle (DMSO) treated controls. Not surprisingly, infection of other RV strains A5-13 (bovine strain) and Wa (Human strain) was also found to be abridged in the presence of quercetin compared to DMSO. The IC₅₀ of quercetin against three RV strains ranges between 2.79 and 4.36 Mm, and S.I. index is greater than 45. Concurrent to the in vitro results, in vivo study in mice model also demonstrated reduced expression of viral proteins and viral titer in the small intestine of quercetin-treated infected mice compared to vehicle-treated infected mice. Furthermore, the result suggested anti-rotaviral activity of quercetin to be interferon-independent. Mechanistic study revealed that the antiviral action of quercetin is co-related with the inhibition of RV-induced early activation of NF-κB pathway. Overall, this study delineates the strong anti-RV potential of quercetin and also proposes it as future therapeutics against rotaviral diarrhea.

Keywords: NF-κB; antiviral therapeutics; phytochemical; quercetin; rotavirus.