Browsing by Subject "Hamster"

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    Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a Syrian hamster model
    (Elsevier, 2022-06-15) Chin, Yuan-Fan; Tang, Wen-Fan; Chang, Yu-Hsiu; Chang, Tein-Yao; Lin, Wen-Chin; Lin, Chia-Yi; Yang, Chuen-Mi; Wu, Hsueh-Ling; Liu, Ping-Cheng; Sun, Jun-Ren; Hsu, Shu-Chen; Lee, Chia-Ying; Lu, Hsuan-Ying; Chang, Jia-Yu; Jheng, Jia-Rong; Chen, Cheng Cheung; Kau, Jyh-Hwa; Huang, Chih-Heng; Chiu, Cheng-Hsun; Hung, Yi-Jen; Tsai, Hui-Ping; Horng, Jim-Tong; Medicine, School of Medicine
    On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3–4 post-infection days). As expected, SARS-CoV-2 induced lung inflammation and hemorrhagic effusions in the alveoli and perivascular areas; additionally, it increased the expression of several immune markers of lung injury – including lung Ki67-positive cells, Iba-1-positive macrophages, and myeloperoxidase-positive neutrophils. Virus-induced lung alterations were significantly attenuated by orally administered PLE. In addition, pretreatment of hamsters with PLE significantly reduced viral loads and immune marker expression. A purified active fraction of PLE was found to confer higher antiviral protection. Notably, PLE prevented SARS-CoV-2-induced increase in serum markers of liver and kidney function as well as the decrease in serum high-density lipoprotein and total cholesterol levels in a dose-dependent fashion. Differently from lung pathology, monitoring of serum biomarkers in Syrian hamsters may allow a more humane assessment of the novel drugs with potential anti-SARS-CoV-2 activity. Our results expand prior research by confirming that PLE may exert an in vivo therapeutic activity against SARS-CoV-2 by attenuating viral loads and lung tissue inflammation, which may pave the way for future clinical applications.
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    Valganciclovir inhibits human adenovirus replication and pathology in permissive immunosuppressed female and male Syrian hamsters
    (MDPI AG (Basel, Switzerland), 2015-03-23) Toth, Karoly; Ying, Baoling; Tollefson, Ann E.; Spencer, Jacqueline; Balakrishnan, Lata; Sagartz, John E.; Buller, Robert Mark; Wold, William S.M.; Department of Biology, School of Science
    Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate) is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5) infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients.