Immunoregulatory Effects of Ethyl-acetate Fraction of Extracts from Tetrastigma Hemsleyanum Diels et. Gilg on Immune Functions of ICR Mice

Objective To evaluate the effects of ethyl-acetate fraction （EAF） of extracts from Tetrastigma hemsleyanum Diels et. Gilg （TDG） on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells （PFCs） at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma （IFN-？） at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha （TNF-α） at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.

Sheng Jiang San, traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidaseinhibition and immune regulation

OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in modern.However,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza efficacy.This study aims to investigate the anti-influenza effect of SJS and its possible mechanisms.METHODS In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney cells.Influenza virus infected BALB/c mice were employed as in vivo model to evaluate the efficacy.Mice challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 d.The survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were measured.The underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of SJS.RESULTS SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner.And IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-1.SJS also protected 50%of mice from influenza virus PR8 infection.The lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated mice.SJS 2 g·L^-1 inhibited 80%of neuraminidase enzymatic activity.SJS also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced mice.CONCLUSION SJS is a useful formulation for treating influenza virus infection.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against SARS-CoV-2.Notably,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted cells.Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells.This work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not.