Hesperetin blocks poxvirus replication with a low tendency to select for drug-resistant viral variants.

In this study, we demonstrated the antiviral efficacy of hesperetin against multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus (VACV), and lumpy skin disease virus (LSDV). The time-of-addition and virus step-specific assays indicated that hesperetin reduces the levels of viral DNA, mRNA, and proteins in the target cells. Further, by immunoprecipitation (IP) of the viral RNA from BPXV-infected Vero cells and a cell-free RNA-IP assay, we demonstrated that hesperetin-induced reduction in BPXV protein synthesis is also consistent with diminished interaction between eukaryotic translation initiation factor eIF4E and the 5' cap of viral mRNA. Molecular docking and MD simulation studies were also consistent with the binding of hesperetin to the cap-binding pocket of eIF4E, adopting a conformation similar to m7GTP binding. Furthermore, in a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane and associated mortality in the chicken embryos. Most importantly, long-term culture of BPXV in the presence of hesperetin did not induce the generation of drug-resistant viral mutants. In conclusion, we, for the first time, demonstrated the antiviral activity of hesperetin against multiple poxviruses, besides providing some insights into its potential mechanisms of action.

Microbial Waterborne Diseases in India: Status, Interventions, and Future Perspectives.

Water plays a vital role as a natural resource since life is unsustainable without it. If water is polluted or contaminated, it results in several health issues among people. Millions of people are infected with waterborne diseases globally, and India is no exception. In the present review, we have analyzed the outbreaks of waterborne diseases that occurred in several Indian states between 2014 and 2020, identified the key infections, and provided insights into the performance of sanitation improvement programs. We noted that acute diarrheal disease (ADD), typhoid, cholera, hepatitis, and shigellosis are common waterborne diseases in India. These diseases have caused about 11,728 deaths between 2014 and 2018 out of which 10,738 deaths occurred only after 2017. The outbreaks of these diseases have been rising because of a lack of adequate sanitation, poor hygiene, and the absence of proper disposal systems. Despite various efforts by the government such as awareness campaigns, guidance on diet for infected individuals, and sanitation improvement programs, the situation is still grim. Disease hotspots and risk factors must be identified, water, sanitation, and hygiene (WASH) services must be improved, and ongoing policies must be effectively implemented to improve the situation. The efforts must be customized to the local environment. In addition, the possible effects of climate change must be projected, and strategies must be accordingly optimized.