Noroviruses are positive-sense, single-stranded RNA viruses belonging to the Caliciviridae family10. Human norovirus (HuNoV) is transmitted via the fecal-oral route and propagates in the gastrointestinal (GI) tract11. It is the most common cause of non-bacterial acute outbreaks of gastroenteritis worldwide across all age groups12. Norovirus has become a global health burden due to its high-sustained viability in environment, high risk of infection with fewer than 100 particles, possibility of causing chronic infection in immune deficient hosts as well as the elderly and infants, and emergence of novel norovirus strains13–16. Despite the breadth of potential antiviral drugs tested in vitro using a HuNoV replicon culture system17, limited studies have validated the efficacy of these drugs in vivo18–20. There are no reports on safe, prophylactic antiviral drugs that could prevent the onset of acute gastroenteritis in immunocompromised hosts. In the absence of approved vaccines and specific antiviral therapies for HuNoV18,21,22, development of prophylactic or therapeutic measures against HuNoV has become the need of the hour.