Efficacy and safety of tenofovir alafenamide fumarate for preventing mother-to-child transmission of hepatitis B virus: a national cohort study.

BACKGROUND: Data on tenofovir alafenamide fumarate (TAF) for preventing mother-to-child transmission of hepatitis B virus (HBV) are lacking. AIMS: To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother-to-child transmission. METHODS: Mothers with chronic HBV infection, positive for hepatitis B e-antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother-to-child transmission were enrolled retrospectively from multiple centres with data collection on mother-infant dyads up to postpartum week 24-28. Primary measurements were the mother-to-child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. RESULTS: Among 71 mothers enrolled, the mean (±SD) age was 30.3 (±2.2) years. TAF was initiated during the second or third trimester and continued to delivery with a mean (±SD) duration of 12.8 (±4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA <200 000 IU/L. Seventy-three infants (two sets of twins) were born from mothers treated with TAF and none had congenital defects or malformations. All infants received HBV immunoglobulin and vaccine at birth with additional HBV vaccinations at one and six months. At age 24-28 weeks, all infants had negative hepatitis B surface antigen and undetectable levels of HBV DNA (<100 IU/mL). Body weight, height, and head circumferences were comparable to national standards for physical development. No severe adverse effects were reported in either mothers or infants. CONCLUSIONS: TAF for highly viraemic mothers effectively prevented mother-to-child transmission of hepatitis B. There were no safety concerns for either mothers or infants with 24-28 weeks of follow up.

Efficacy of telbivudine and entecavir against virus reactivation in HBeAg-patients undergoing chemotherapy.

The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg-) patients receiving chemotherapy (C/T).Records of 260 HBeAg-, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.Of the 126 HBeAg- patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ±â€Š23.1 to 87.3 ±â€Š21.3 ml/minute/1.73 m (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ±â€Š32.2 to 85.5 ±â€Š85.7 ml/minute/1.73 m (P = .0009).The absolute risk reduction ARR is 27.8% - 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% - 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg-status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.

Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: a retrospective study.

BACKGROUND: The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS. METHODS: We retrospectively recruited HBeAg-positive CHB patients receiving liver biopsy and NA monotherapy. The baseline clinical characteristics and cumulative incidence of HBeAg seroclearance were compared between patients with and without HS and age/gender-matched subgroup analysis was performed. RESULTS: A total of 196 patients were enrolled from 2003 April to 2016 October. The mean age was 39.6 ± 11.2 years, 142 (72.4%) were males and 94 (48%) had histological evidence of HS. Median treatment duration and follow-up period were 24.3 months and 54.9 months, respectively. HBeAg seroclearance was achieved in 56/102 (54.9%) and 54/94 (57.4%) patients with and without HS, respectively (p = 0.830). The 5-year cumulative incidence of HBeAg seroclearance in patients with and without HS was 62.8 and 67.7% in overall population (p = 0.398) and 62.4 and 66.9% in age/gender-matched subgroups (p = 0.395), respectively. The rate of HBeAg seroclearance was comparable between patients with or without HS in different NA monotherapy (all p > 0.05). CONCLUSIONS: HS had no significant impact on HBeAg seroclearance in HBeAg-positive CHB patients with NA monotherapy during long-term follow-up.

Anti-hepatitis B virus activity of swertisin isolated from Iris tectorum Maxim.

ETHNOPHARMACOLOGICAL RELEVANCE: Iris tectorum Maxim (I. tectorum, Yuan Wei in Chinese) is a common and traditional Chinese medicinal herb that be used to treat liver-related diseases. However, the anti-HBV activity of I. tectorum and its isolates has not been systemically studied. AIM OF THE STUDY: To screen the active part of I. tectorum and systemically evaluate their anti-HBV activity. MATERIALS AND METHODS: In this study, a series of compounds from I. tectorum were evaluated for their ability to inhibit HBV replication. Swertisin showed a significant inhibitory function on HBV replication. Then, the suppression effect of different concentrations of swertisin in HBsAg, HBeAg and HBV DNA level in HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were comprehensive evaluated, respectively. Moreover, the anti-HBV effects of swertisin were confirmed in HBV transgenic mice model. RESULTS: Among these compounds, swertisin strongly inhibited the HBsAg, HBeAg and HBV DNA level in a dose-dependent manner in HepG2.2.15 cells and HBV-infected HepG2-NTCP cells. Furthermore, swertisin showed a significant inhibition role on HBV replication in HBV transgenic mice model, the inhibition effect of which was enhanced when combined with ETV. CONCLUSIONS: We have identified that swertisin can inhibit HBeAg and HBsAg production, as well as HBV DNA in vitro and in vivo. This study show that we may found a novel compound isolated from traditional Chinese medicines with potent anti-HBV function.

The combination therapy of Peginterferonα and entecavir for HBeAg-positive chronic hepatitis B with high HCC risk.

The population of HBV infection with family history of hepatocellular carcinoma (HCC) is the high risk group for the development of HCC. The aim of this study was to evaluate the effect of the de novo combination therapy including pegylated-interferon α-2a (PEG-IFNα-2a) and entecavir (ETV) in this high risk population. The study recruited 58 Hepatitis B e Antigen (HBeAg)-Positive CHB patients patients with HBV-DNA > 107 IU/mL, genotype B or C and HCC family history and were treated for 48 weeks. Patients without HBeAg loss at the 48th week were 40 patients and extended the combination therapy to 96 weeks. All patients were followed up to 120 weeks. The rate of HBeAg loss and HBsAg loss was 12/40(30.0%) and 2/40(5.0%) at week 120 respectively. When logistic regression analysis was used to identify viables of HBeAg loss, HBV-DNA levels <20 IU/mL at week 48 was found to have a 6.02 fold increased probability (95% CI = 1.17-30.40, P = .03) of HBeAg loss. Patients with HBV-DNA levels <20 IU/mL at week 48 had a high probability of HBeAg loss 8/17(47.1%), HBsAg loss 2/17(11.8%), compared to 4/23(17.4%), 0/23(0%) in patients with HBV-DNA ≥ 20 IU/mL. Combination therapy for 96 weeks was well tolerated. During the combination therapy, low-level viremia during treatment is reversely associated with response. The combination therapy of PEG-IFNα and ETV was suggested to extend to 96 weeks when HBV-DNA was completed suppressed at week 48.

Direct Inhibition of Hepatitis B e Antigen by Core Protein Allosteric Modulator.

Hepatitis B e antigen (HBeAg) is an important immunomodulator for promoting host immune tolerance during chronic hepatitis B (CHB) infection. In patients with CHB, HBeAg loss and seroconversion represent partial immune control of CHB infection and are regarded as valuable endpoints. However, the current approved treatments have only a limited efficacy in achieving HBeAg seroconversion in HBeAg-positive patients. Hepatitis B virus (HBV) core protein has been recognized as an attractive antiviral target, and two classes of core protein allosteric modulator (CpAM) have been discovered: the phenylpropenamides (PPAs) and the heteroaryldihydropyrimidines (HAPs). However, their differentiation and potential therapeutic benefit beyond HBV DNA inhibition remain to be seen. Here, we show that in contrast to PPA series compound AT-130, a HAP CpAM, HAP_R01, reduced HBeAg levels in multiple in vitro and in vivo HBV experimental models. Mechanistically, we found that HAP_R01 treatment caused the misassembly of capsids formed by purified HBeAg in vitro. In addition, HAP_R01 directly reduces HBeAg levels by inducing intracellular precore protein misassembly and aggregation. Using a HAP_R01-resistant mutant, we found that HAP_R01-mediated HBeAg and core protein reductions were mediated through the same mechanism. Furthermore, HAP_R01 treatment substantially reduced serum HBeAg levels in an HBV mouse model. Conclusion: Unlike PPA series compound AT-130, HAP_R01 not only inhibits HBV DNA levels but also directly reduces HBeAg through induction of its misassembly. HAP_R01, as well as other similar CpAMs, has the potential to achieve higher anti-HBeAg seroconversion rates than currently approved therapies for patients with CHB. Our findings also provide guidance for dose selection when designing clinical trials with molecules from HAP series.

An Effective Antiviral Approach Targeting Hepatitis B Virus with NJK14047, a Novel and Selective Biphenyl Amide p38 Mitogen-Activated Protein Kinase Inhibitor.

Despite recent advances in therapeutic strategies against hepatitis B virus (HBV) infection, chronic hepatitis B remains a major global health burden. Recent studies have shown that targeting host factors instead of viral factors can be an effective antiviral strategy with low risk of the development of resistance. Efforts to identify host factors affecting viral replication have identified p38 mitogen-activated protein kinase (MAPK) as a possible target for antiviral strategies against various viruses, including HBV. Here, a series of biphenyl amides were synthesized as novel p38 MAPK selective inhibitors and assessed for their anti-HBV activities. The suppression of HBV surface antigen (HBsAg) production by these compounds was positively correlated with p38 MAPK-inhibitory activity. The selected compound NJK14047 displayed significant anti-HBV activity, as determined by HBsAg production, HBeAg secretion, and HBV production. NJK14047 efficiently suppressed the secretion of HBV antigens and HBV particles from HBV genome-transfected cells and HBV-infected sodium taurocholate cotransporting polypeptide-expressing human hepatoma cells. Furthermore, NJK14047 treatment resulted in a significant decrease of pregenomic RNA and covalently closed circular DNA (cccDNA) of HBV in HBV-harboring cells, indicating its ability to inhibit HBV replication. Considering that suppression of HBsAg secretion and elimination of cccDNA of HBV are the major aims of anti-HBV therapeutic strategies, the results suggested the potential use of these compounds as a novel class of anti-HBV agents targeting host factors critical for viral infection.

Hepatitis B virus long-term impact of antiviral therapy nucleot(s)ide analogues (NUCs).

The goal of antiviral therapy is to improve the quality of life and survival of patients with chronic hepatitis B (CHB) by halting the progression to cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC), thus preventing anticipated liver-related death. Oral administration of potent and less resistance-prone nucleot(s)ide analogues (NUCs), such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF) has become the most popular treatment strategy worldwide because of their excellent efficacy and safety profile as well as easy management confirmed in both registration trials and in clinical practice studies. Long-term administration of ETV or TDF suppresses HBV replication in >95% of patients, resulting in biochemical remission, histological improvement including the regression of cirrhosis and prevention or reversal of clinical decompensation but not the development of HCC, particularly in patients with cirrhosis. Moreover, NUCs can be administered to all patients including those with severe liver disease, the elderly and in those who do not respond, are unwilling to take or have contraindications to interferon. The need for long-term, perhaps indefinite, treatment is the main limitation of NUCs therapy with the associated costs, unknown long-term safety and the low rates of hepatitis B surface antigen (HBsAg) seroclearance, which is still the best stopping rule for NUCs-treated patients with cirrhosis.

Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors.

In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have employed bioisosterism and hybrid pharmacophore-based strategy to explore the chemically diverse space of bioactive compounds. In this article, the original thiazole platform was replaced with pyrazole scaffold to yield the optimal pharmacophore moieties in order to generate novel non-nucleoside HBV inhibitors with desirable potency. Some of the new compounds were able to inhibit HBV activity in the low micromolar range. In particular, compound 6a3 displayed the most potent activity against the secretion of HBsAg and HBeAg with IC50 of 24.33 µM and 2.22 µM, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was investigated, which may help designing more potent molecules.

A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation.

A series of oleanolic acid derivatives were synthesized by diverse reactions, including the introduction of conjugated alkadiene and epoxy ring moieties formed by means of photosensitized oxidation. Eosin Y was used as photosensitizer during this process. Next the cytotoxicity of the products was evaluated on HepG2.2.15 cells to determine the appropriate treatment concentration for the subsequent experiments. Most of the OA derivatives exhibited anti-HBV antigens secretion activity in HepG2.2.15 cells. Among the tested compounds, OA-4 (3.13 µg/mL) showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with inhibitory ratios of 90.52% ± 1.78%, 31.55% ± 3.65%, and 94.57% ± 3.11% after 6 days, respectively. Besides, OA-4 was further investigated in a duck model with DHBV infection. When OA-4 was administered at a dosage of 500 mg/kg, the results revealed a significant inhibitory effects of DHBV at 19.94% ± 2.87%, 28.80% ± 3.62% and 29.25% ± 2.65% at days 5, 10, and 3 after the cessation of OA-4 treatment, respectively. It's worth noting that OA-4 is superior to lamivudine in the inhibition of rebound of viral replication rate. The structure-activity relationships of OA derivatives had been preliminary discussed, which should be useful to explore further novel anti-HBV agents.

Genetic variation in STAT4 predicts response to interferon-α therapy for hepatitis B e antigen-positive chronic hepatitis B.

UNLABELLED: Interferon (IFN)-α is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFNα treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFNα-2b (n = 224) or pegylated IFNα-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level <2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFNα-2b and pegylated IFNα-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFNα-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFNα-2a therapy (18.0% versus 41.2%, P = 9.74 × 10(-5) ). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10(-6) ). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. CONCLUSION: STAT4 rs7574865 is a reliable predictor of response to IFNα therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB.

Hepatitis B: encouraging the use of interferon.

PURPOSE OF REVIEW: Hepatitis B is a major cause of hepatocellular carcinoma and liver cirrhosis. Interferon (IFN)-based therapies provide the highest likelihood of achieving off-treatment virological and serological control although their use is often avoided because of the side-effect profile. We review recent developments regarding the use of IFN in the treatment of chronic hepatitis B, including proposed strategies to enhance efficacy while limiting treatment exposure for patients who are unlikely to achieve acceptable treatment endpoints. RECENT FINDINGS: The utility of host genetics (human leukocyte antigen associations and interleukin 28B) is yet to be defined. In hepatitis B e antigen (HBeAg)-positive disease, add-on IFN therapy to patients on entecavir may allow curtailment of nucleos(t)ide analogue treatment. In HBeAg-negative disease, an on-treatment stopping rule that measures decline of hepatitis B surface antigen and hepatitis B virus DNA at 12 and 24 weeks may identify up to two-thirds of poor responders. Prolonging IFN therapy to 96 weeks in patients with HBeAg-negative disease may improve virological and serological response rates. The combination of telbivudine and IFN therapy is contraindicated because of high rates of peripheral neuropathy. SUMMARY: These findings need to be confirmed in larger trials before they can be instituted into routine clinical practice.

A coumarin lignanoid from the stems of Kadsura heteroclita.

Coumarinlignan (1), possessing a unique coumarin-containing lignan skeleton, was isolated from the stems of Kadsura heteroclita. Its structure and absolute configuration were determined by spectroscopic techniques, especially 2D NMR and X-ray crystallographic data analyses. The proposed biosynthetic pathway is discussed. This new compound showed good anti-HBV activity against HBeAg and HBsAg, and moderate anti-fibrotic and neuroprotective activities.

Antiviral activity of a nanoemulsion of polyprenols from ginkgo leaves against influenza A H3N2 and hepatitis B virus in vitro.

UNLABELLED: In order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (GBP)) in the human body, a GBP nanoemulsion was prepared, and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro. METHODS: A GBP nanoemulsion was prepared by inversed-phase emulsification (IPE). Next, we investigated the antiviral activity of the GBP nanoemulsion on influenza A H3N2 and hepatitis B virus in vitro by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenlytetrezolium bromide) method. ELISA and the fluorescent quantitative PCR method were used to measure the content of HBsAg, HBeAg and DNA virus in human samples. RESULTS: The GBP nanoemulsion exhibited uniformity at an average particle size 97 nm with a hydrophilic-lipophilic balance (HLB) of 9.5. GBP is non-toxic to normal cells, hepatitis B virus DNA, hepatitis B virus antigen and HepG2215. Furthermore, GBP could reach a 70% virucidal activity and a 74.9% protection rate (*** p < 0.001) on MDCK cells infected with H3N2 virus at a high concentration of 100 µg/mL. GBP had a good inhibition rate on HBsAg (52.11%, ** p < 0.01) at 50 µg/mL and Day 9 of incubation, and a 67.32% inhibition effect on HBeAg at a high concentration of 100 µg/mL and Day 9. GBP had good inhibition on HBV DNA with CT 18.6 and lower copies (** p < 0.01) at a middle concentration of 12.5 to 25 µg/mL. CONCLUSIONS: The GBP nanoemulsion was very stable and non-toxic and had very strong antiviral activity against influenza A H3N2 and hepatitis B virus in vitro. The inhibitory effects and reactive mechanisms were similar to the drug, 3TC; by lengthening the incubation time and increasing the drug concentration, GBP has promising potential as an antiviral drug.

UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatitis B induced by HBV is a serious health problem. Artemisia capillaris (Yin-Chen) has long been used to treat hepatitis in traditional Chinese medicine. Coumarins, flavonoids and organic acids were revealed as its hepatoprotective and choleretic components, but its anti-HBV active components remain unknown. This current study focused on its anti-HBV active constituents by various chromatographic methods. MATERIAL AND METHODS: LC/MS and bioassay-guided fractionation on the active extract of Artemisia capillaris led to the isolation of nine chlorogenic acid analogues. Structures of the isolates were elucidated by MS/MS and NMR techniques. Anti-HBV assay was performed on HepG 2.2.15 cell line in vitro: reduction of HBsAg and HBeAg secretions was measured by an ELISA method; inhibition of HBV DNA replication was monitored by real-time quantitative PCR and cellular toxicity was assessed by a MTT method. RESULTS: The 90% ethanol extract of Artemisia capillaris (Fr. AC) showed significantly inhibitory activity on HBV DNA replication with an IC50 value of 76.1 ± 3.9 µg/mL and low cytotoxic effects (SI>20.1). To clarify its active constituents, the extract was further separated into 3 sub-fractions (AC-1, AC-2 and AC-3), of which Fr. AC-2 was the most active fraction against HBeAg secretion and HBV DNA replication with IC50 values of 44.2 ± 2.8 and 23.2 ± 1.9 µg/mL. Nine chlorogenic acid analogues were detected from the active part (Fr. AC-2) by a LC/MS technique and further separated by a HPLC method. The isolates were determined as chlorogenic acid (1), cryptochlorogenic acid (2), neochlorogenic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), chlorogenic acid methyl ester (7), cryptochlorogenic acid methyl ester (8), neochlorogenic acid methyl ester (9). Compounds 1-6 possessed potent activity against HBV DNA replication with IC50 values in the range of 5.5 ± 0.9-13.7 ± 1.3 µM. Di-caffeoyl analogues (4-6) also exhibited activity against the secretions of HBsAg and HBeAg. Esterified analogues (7-9) showed dramatically decreased anti-HBV activity, indicating that carboxyl group is closely associated to the anti-HBV activity. CONCLUSIONS: This investigation was focused on the active fractions of Artemisia capillaris and their active compositions, which showed that Fr. AC-2 was the main active section of Artemisia capillaris and chlorogenic acid analogues were the main constituents contributing to its anti-HBV activity. These results support the ethnopharmacological use of Artemisia capillaris as anti-HBV agents.

Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris.

Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-ß-D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-ß-D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC50 values of 15.02 µM (SI=111.3), 9.00 µM (SI=185.9) and 12.01 µM (SI=139.2).

Anti-hepatitis B virus and cytotoxic diterpenoids from Isodon lophanthoides var. gerardianus.

Four new diterpenoides, isolophanthins A-D (1-4) together with seven known abietane diterpenoides (5-11), have been isolated from Isodon lophanthoides var. gerardianus. The new diterpenoides were elucidated by spectroscopic analysis. Some of them showed significant activities against HBsAg and HBeAg of hepatitis B virus in Hep G 2.2.15 cells, as well as the human tumor cell lines, HL-60, A-549, MOLT-4, and BEL-7402.

[In vitro study on the anti-HSV-1 and HBV activities of extracts from the fruit of Eucalyptus maidenii].

OBJECTIVE: To investigate the antiviral activities of three kinds of extracts from the fruit of Eucalyptus maidenii against herpes simplex virus typel and Hepatitis B Virus. METHODS: Cytotoxicity of extracts on Vero cell lines were estimated using MTT method and anti-HSV-1 activity was observed and determined with CPE and plaque reduction assay. The inhibitory effects of extracts on HBsAg and HBeAg secretion in HepG2.2.15 cell culture were detected using ELISA. RESULTS: Aqueous extract (pl8-E3) had conspicuous anti-HSV-1 activity, the IC50 was 126.77 microg/mL,but the EtOAc extracts( pl8-E1 )and MeOH extracts (pl8-E2) showed little anti-HSV-1 activity. None of these extracts had significant inhibitory eflect on HBsAg and HBeAg secretion in HepG2.2.15 cell culture. CONCLUSION: Aqueous extract(p18-E3) from the fruit of Eucalyptus maidenii has conspicuous anti-HSV-1 activity. It could inactivate virus directly,and inhibit virus attachment,but had no influence on virus penetration. The mechanism that p18-E3 inactivates virus might involve in viral envelope alteration.

Antiviral therapy for chronic hepatitis B.

The goal of antiviral therapy for chronic hepatitis B is to prevent the development of cirrhosis and hepatocellular carcinoma. End points, including viral suppression, alanine aminotransferase normalization, hepatitis B e antigen loss, hepatitis B surface antigen loss, and improvement in liver histology, are used to determine treatment success. Treatment is based on hepatitis B virus (HBV) replication status and stage of liver disease, modulated by the age of the patient, hepatitis B e antigen (HBeAg) status and patient preference. Seven therapies are approved, including two formulations of interferon and five orally administered nucleos(t)ide analogs. These therapies are effective in suppressing HBV replication and have also been shown to prevent disease progression.

Llama-derived single-domain intrabodies inhibit secretion of hepatitis B virions in mice.

UNLABELLED: Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single-domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV. VHHs, when expressed and retained in the endoplasmic reticulum as intrabodies, reduced levels of secreted hepatitis B surface antigen (HBsAg) particles in a cellular HBV model. In a hydrodynamics-based HBV mouse model, these intrabodies caused a marked reduction in HBsAg concentrations and a 10- to >100-fold reduction in the concentration of HBV virions in plasma. CONCLUSION: VHHs potently inhibited secretion of HBV virions in vivo, showing that this approach might be useful in the treatment of HBV. To our knowledge, this is the first report of intrabody-mediated inhibition of viral secretion in mammals.