Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

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

Bortezomib Eliminates Persistent Chlamydia trachomatis Infection through Rapid and Specific Host Cell Apoptosis

Chlamydia trachomatis, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this finding, this study showed that both bortezomib (BTZ) and ixazomib (IXA), anticancer drugs characterized by proteasome inhibitors, have intensive inhibitory activity against Chlamydia. Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of Chlamydia (BTZ, IC50 = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as Escherichia coli. BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, Chlamydia-infected cells that induced a persistent infection state were selectively eliminated by BTZ treatment, whereas uninfected cells survived. These results strongly suggested the potential of boron compounds based on hydrophobic dipeptides for treating chlamydial infections, including persistent infections, which may be useful for future therapeutic use in chlamydial infectious diseases

Longitudinal Dynamics of SARS-CoV-2 IgG Antibody Responses after the Two-Dose Regimen of BNT162b2 Vaccination and the Effect of a Third Dose on Healthcare Workers in Japan

Analysis of longitudinal dynamics of humoral immune responses to the BNT162b2 COVID-19 vaccine might provide useful information to predict the effectiveness of BNT162b2 in preventing SARS-CoV-2 infection. Herein, we measure anti-RBD IgG at 1, 3 and 6 months (M) after the second dose of BNT162b2, and at 1 M after a third dose of BNT162b2 vaccination in 431 COVID-19-naïve healthcare workers (HCWs) in Japan. All HCWs mounted high-anti-RBD IgG responses after the two-dose regimen of BNT162b2 vaccinations. Older persons and males presented lower anti-RBD IgG responses than younger adults and females, respectively. The decay in anti-RBD IgG started from 1 M after the second dose of BNT162b2 and anti-RBD IgG titers dropped to nearly one-tenth at 6 M after the second vaccination. Subsequently, the participants received a third dose of BNT162b2 at 8 M after the second dose of BNT162b2 vaccine. Anti-RBD antibody titers 1 M after the third dose of BNT162b2 increased seventeen times that of 6 M after the second dose, and was twice higher than the peak antibody titers at 1 M after the second dose of vaccination. The negative effect of age for the male gender on anti-RBD IgG antibody titers was not observed at 1 M after the third dose of BNT162b2 vaccine. There were no notable adverse events reported, which required hospitalization in these participants. These results suggest that the third dose of BNT162b2 safely improves humoral immunity against SARS-CoV-2 with no major adverse events