We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H+ ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.
A 24yearold woman felt sore throat on day 1 of symptom onset and became feverish and had chills on day 2. She came to our clinic on day 3, and was diagnosed as having a cold. Subsequently, severe acute respiratory syndrome coronavirus 2 (SARSCoV2) gene was detected in her nasopharyngeal swab by PCR ; therefore, she was isolated in a hotel room. On day 5, she started taking maoto, traditional Kamp medicine, because a high fever and nausea continued after her moving to the hotel. After taking maoto, perspiration was noted, and the fever resolved. Treatment with maoto was stopped for one day due to worsening of the nausea. The result of a new PCR was positive on day 7, but showed a decreased viral load. Maoto has been shown to be effective against influenza. The present case suggests that maoto may also be effective for novel coronavirus infection (coronavirus disease 2019 ; COVID19) with influenzalike symptoms. In addition, since nausea may occur as a side effect of maoto, additional combination with other Kampo drug(s) may be considered.
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