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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus are global threats to human health. The application of effective virucidal agents, which contribute to the inactivation of viruses on hands and environmental surfaces, is important to facilitate robust virus infection control measures. Naturally derived virucidal disinfectants have attracted attention owing to their safety and eco-friendly properties. In this study, we showed that multiple Japanese Saxifraga species-derived fractions demonstrated rapid, potent virucidal activity against the SARS-CoV-2 ancestral strain and multiple variant strains, IAV, and two human norovirus surrogates: feline calicivirus (FCV) and murine norovirus (MNV). Condensed tannins were identified as active chemical constituents that play a central role in the virucidal activities of these fractions. At a concentration of 25 mg/mL, the purified condensed tannin fraction Sst-2R induced significant reductions in the viral titers of the SARS-CoV-2 ancestral strain, IAV, and FCV (reductions of $3.13, $3.00, and 2.50 log10 50% tissue culture infective doses [TCID50]/mL, respectively) within 10 s of reaction time. Furthermore, at a concentration of 100 mg/mL, Sst-2R induced a reduction of 1.75 log10 TCID50/mL in the viral titers of MNV within 1 min. Western blotting and transmission electron microscopy analyses revealed that Sst-2R produced structural abnormalities in viral structural proteins and envelopes, resulting in the destruction of viral particles. Furthermore, Saxifraga species-derived fraction-containing cream showed virucidal activity against multiple viruses within 10 min. Our findings indicate that Saxifraga species-derived fractions containing condensed tannins can be used as disinfectants against multiple viruses on hands and environmental surfaces. IMPORTANCE SARS-CoV-2, IAV, and norovirus are highly contagious pathogens. The use of naturally derived components as novel virucidal/antiviral agents is currently attracting attention. We showed that fractions from extracts of Saxifraga species, in the form of a solution as well as a cream, exerted potent, rapid virucidal activities against SARS-CoV-2, IAV, and surrogates of human norovirus. Condensed tannins were found to play a central role in this activity. The in vitro cytotoxicity of the purified condensed tannin fraction at a concentration that exhibited some extent of virucidal activity was lower than that of 70% ethanol or 2,000 ppm sodium hypochlorite solution, which are popular virucidal disinfectants. Our study suggests that Saxifraga species-derived fractions containing condensed tannins can be used on hands and environmental surfaces as safe virucidal agents against multiple viruses. [ABSTRACT FROM AUTHOR]

Background CC-chemokine receptor 7 (CCR7), a known lymph node homing receptor for immune cells, has been reported as a key molecule in lymph node metastasis. We hypothesized a clinicopathological correlation and functional causality between CCR7 expression and lymph node metastasis in patients with esophageal squamous cell carcinoma (ESCC). Methods We performed immunohistochemical analysis of 105 consecutive and 61 exclusive pathological T1 ESCC patients, followed by adhesion assay and in vivo experiment using a newly developed lymph node metastasis mouse model. The adhesive ability in response to CC-chemokine ligand 21/secondary lymphoid-tissue chemokine (CCL21/SLC) was assessed in the presence or absence of lymphatic endothelial cells and anti-CCR7 antibody. We established a heterotopic transplantation mouse model and analyzed lymph node metastasis by quantitative real-time RT-PCR. Results Positive CCR7 expression in immunohistochemistory was detected in 28 (27%) of 105 consecutive patients and 17 (28%) of 61 T1 patients, which significantly correlated with lymph node metastasis (p = 0.037 and p = 0.040, respectively) and poor five-year survival (p = 0.013 and p = 0.012, respectively). Adhesion assay revealed an enhanced adhesive ability of CCR7-expressing cells in response to CCL21/SLC, in particular, in the presence of lymphatic endothelial cells (p = 0.005). In the mouse model, lymph nodes from mice transplanted with CCR7-expressing cells showed significantly higher DNA levels at 5 weeks (p = 0.019), indicating a high metastatic potential of CCR7-expressing cells. Conclusion These results demonstrated the significant clinicopathological relationship and functional causality between CCR7 expression and lymph node metastasis in ESCC patients. [ABSTRACT FROM AUTHOR]

AbstractPhotodynamic therapy (PDT) is a noninvasive optical treatment method in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with broadband red light. Coupling photosensitizers with a specific antibody may allow this approach to target specific cancers. This study determines the antitumor efficacy of coupling verteporfin (Visudyne®), a hydrophobic polyporphryin oligomer, with an antiepidermal growth factor receptor (anti-EGFR) antibody. Poly[2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-nitrophenylcarbonyloxyethyl methacrylate] (PMBN) was conjugated with an anti-EGFR antibody and mixed with verteporfin (verteporfin–PMBN–antibody complex). Tumor-bearing mice were intravenously injected with the verteporfin–PMBN–antibody complex or verteporfin plus PMBN without the antibody. Irradiation was conducted at 640 nm with a dose of 75 J/cm2. The fluorescence intensity in A431 cells in vitrowas threefold higher after exposure to verteporfin–PMBN–antibody complex than after exposure to verteporfin–PMBN. In A431 tumor-bearing mice, the intratumor concentration of verteporfin was 9.4 times higher than that of the skin, following administration of the verteporfin–PMBN–antibody complex. Tumor size significantly decreased within 8 days in mice treated with verteporfin–PMBN–antibody complex compared with those treated with verteporfin–PMBN. PDT using a PMBN–verteporfin–antibody complex offers a promising anticancer therapy. [ABSTRACT FROM AUTHOR]

As a result of the novel coronavirus disease 2019 pandemic, strengthening control measures against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has become an urgent global issue. In addition to antiviral therapy and vaccination strategies, applying available virucidal substances for SARS-CoV-2 inactivation is also a target of research to prevent the spread of infection. Here, we evaluated the SARS-CoV-2 inactivation activity of a copper iodide (CuI) nanoparticle dispersion, which provides Cu1 ions having high virucidal activity, and its mode of actions. In addition, the utility of CuI-doped film and fabric for SARS-CoV-2 inactivation was evaluated. The CuI dispersion exhibited time-dependent rapid virucidal activity. Analyses of the modes of action of CuI performed by Western blotting and real-time reverse transcription-PCR targeting viral proteins and the genome revealed that CuI treatment induced the destruction of these viral components. In this setting, the indirect action of CuI-derived reactive oxygen species contributed to the destruction of viral protein. Moreover, the CuI-doped film and fabric demonstrated rapid inactivation of the SARSCoV-2 solution in which the viral titer was high. These findings indicated the utility of the CuI-doped film and fabric as anti-SARS-CoV-2 materials for the protection of hightouch environmental surfaces and surgical masks/protective clothes. Throughout this study, we demonstrated the effectiveness of CuI nanoparticles for inactivating SARSCoV-2 and revealed a part of its virucidal mechanism of action. [ABSTRACT FROM AUTHOR]