Anti-herpes Simplex Virus Activity Research Articles

Nuciferol C, a new sesquineolignan dimer from Cocos nucifera L.: bioactivity and theoretical investigation.

Nuciferol C (NC), an undescribed dimer of nuciferol B (NB), was isolated from the endocarp of Cocos nucifera L. The planar structure of NC was determined using 1D- and 2D-NMR spectroscopy as well as high resolution MS spectrometry. The absolute configuration was concluded based on analysis of NOESY spectra. NC showed cytotoxic activity against colon cancer cells (CaCo-2) with an IC50 value of 76 μM, and significantly decreased the expression of human epidermal growth factor receptor (EGFR) and tumor necrosis factor alpha (TNF-α) in CaCo-2 as compared with untreated cells by 39% and 33%, respectively (p < 0.05). In addition, NC exhibited anti-herpes simplex virus (HSV-I) activity with an IC50 value of 23 μM. In silico study of NC was implemented at three levels: density functional theory (DFT) was used to study its electronic properties, molecular mechanics was used to estimate the docking results, and finally, molecular dynamic simulation was used to study the behavior and stability of NC inside the active site of the target protein of HSV-1.

Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from Apis mellifera and Apis florea Venom.

Herpes simplex virus (HSV) is known to cause cold sores and various diseases in humans. Importantly, HSV infection can develop latent and recurrent infections, and it is also known to cause inflammation. These infections are difficult to control, and effective treatment of the disease remains a challenge. Thus, the search for new antiviral and anti-inflammatory agents is a necessity. Melittin is a major peptide that is present in the venom of the honeybee. It possesses a number of pharmacological properties. In this study, the effects of the melittin peptides from A. mellifera (MEL-AM) and A. florea (MEL-AF) against HSV-1 and HSV-2 were evaluated at different stages during the viral multiplication cycle in an attempt to define the mode of antiviral action using plaque reduction and virucidal assays. The results revealed a new finding that melittin at 5 µg/mL demonstrated the highest inhibitory effect on HSV through the direct inactivation of viral particles, and MEL-AF displayed a greater virucidal activity. Moreover, melittin was also observed to interfere with the process of HSV attachment to the host cells. MEL-AM exhibited anti-HSV-1 and anti-HSV-2 effects with EC50 values of 4.90 ± 0.15 and 4.39 ± 0.20 µg/mL, while MEL-AF demonstrated EC50 values of 4.47 ± 0.21 and 3.95 ± 0.61 µg/mL against HSV-1 and HSV-2, respectively. However, non-cytotoxic concentrations of both types of melittin produced only slight degrees of HSV-1 and HSV-2 inhibition after viral attachment, but melittin at 5 µg/mL was able to reduce the plaque size of HSV-2 when compared to the untreated group. In addition, MEL-AM and MEL-AF also exhibited anti-inflammatory activity via the inhibition of nitric oxide production in LPS-stimulated RAW 264.7 macrophage cells, and they were also found to down-regulate the expressions of the iNOS, COX-2 and IL-6 genes. The highest inhibition of IL-6 mRNA expression was found after treatment with 10 µg/mL of MEL-AM and MEL-AF. Therefore, melittin peptides have displayed strong potential to be used as an alternative treatment for HSV infection and inflammatory diseases in the future.

Anti-herpes simplex virus activities and mechanisms of marine derived compounds.

Herpes simplex virus (HSV) is the most widely prevalent herpes virus worldwide, and the herpetic encephalitis and genital herpes caused by HSV infection have caused serious harm to human health all over the world. Although many anti-HSV drugs such as nucleoside analogues have been ap-proved for clinical use during the past few decades, important issues, such as drug resistance, toxicity, and high cost of drugs, remain unresolved. Recently, the studies on the anti-HSV activities of marine natural products, such as marine polysaccharides, marine peptides and microbial secondary metabolites are attracting more and more attention all over the world. This review discusses the recent progress in research on the anti-HSV activities of these natural compounds obtained from marine organisms, relating to their structural features and the structure-activity relationships. In addition, the recent findings on the different anti-HSV mechanisms and molecular targets of marine compounds and their potential for therapeutic application will also be summarized in detail.

Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark

Ethnopharmacological relevanceExcept for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. This especially concerns plants with ethnomedical records on their use in treatment of viral infections. Aim of the studyTo identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. Materials and methodsThe ethno-medical survey was performed in the Kagera region of Tanzania. The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. ResultsTHPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 μg/ml (selectivity index >476) and 0.14 μg/ml (selectivity index >7143) respectively. The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. ConclusionsAltogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions.

WITHDRAWN: Polyphenolic-protein-polysaccharide conjugates from Spica of Prunella vulgaris: Chemical profile and anti-herpes simplex virus activities

Previous studies showed that the water extract (PVW) from Spica of Prunella vulgaris Linn. (Labiatae) exerts anti-herpes simplex virus (HSV) activity. Evaluation the antiviral activity of the graded ethanol precipitations indicated that 30% ethanol precipitate (PVE30) was the active principle of water extract (PVW). Further activity-oriented separation of PVE30 through salting-out method revealed that the anti-HSV activity of P. vulgaris glycoconjugates (PVG) was more potent than PVE30 and PVW, 2-fold and 4-fold, respectively. UPLC-QTOF-MS/MS, FT-IR and NMR techniques identified PVG as a type of polyphenolic-protein-polysaccharides (PPPs) with an average molecular weight of 41.69 kDa. PVG was composed of dibenzylbutyrolactone lignan units, and rich in galacturonic acid, xylose, rhamnose, rhamnose, arabinose, glucose monosaccharide units, glutamic acid and aspartic acid. Further in vitro antiviral testing confirmed that PVG substantially and stably inhibited acyclovir (ACV) resistant HSV strains; its inhibitory action was even better than the positive control ACV. Overall, our findings support PVG as a potential drug resource for anti-HSV therapy.

Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

In vitro and in vivo anti-herpes simplex virus activity of monogalactosyl diacylglyceride from Coccomyxa sp. KJ (IPOD FERM BP-22254), a green microalga.

A monogalactosyl diacylglyceride (MGDG) was isolated as an antiviral component from Coccomyxa sp. KJ (IPOD FERM BP-22254) via bioassay-guided fractionation. α-Linolenic acid (C18:3) and 7,10,13-hexadecatrienoic acid (C16:3) accounted for approximately 72% and 23%, respectively, of the MGDG total fatty acids of the MGDG. The MGDG showed virucidal activity against herpes simplex virus type 2 (HSV-2), a pathogen that causes genital herpes. Physical changes in HSV-2 shape were observed after treatment with MGDG, including a decrease in particle size, and possible damage to the viral envelope, as assessed using electron microscopy. In accordance with the morphological findings, virus particles lost their ability to bind to host cells. HSV-2 treated with high concentrations of MGDG resulted in no pathogenicity in an animal model, indicating that MGDG exhibits irreversible virucidal activity against HSV-2 particles. In the animal model of HSV-2-induced genital herpes, intravaginally administered MGDG exerted a prophylactic effect by suppressing viral yields in the genital cavity and formation of herpetic lesions, resulting in a higher survival rate in treated mice than control mice administered solvent. Thus, MGDG offers a novel prophylactic option against HSV infections.

Anti-Herpes Simplex virus and antibacterial activities of Graptopetalum paraguayense E. Walther leaf extract: a pilot study

Graptopetalum paraguayense E. Walther (GP) belongs to the Crassulaceae family and has several health benefits. In the present study we evaluated the cytotoxic, anti-Herpes Simplex virus (HSV) and antibacterial activities of a total methanol/water GP extract. The results from the cytotoxicity investigation of the tested extract showed a high cell tolerable concentration range. The GP extract demonstrated a significant inhibitory effect on the wild-type HSV-1 strain Victoria in a concentration of 0.0001 mg/mL equal to the maximal nontoxic concentration (with 97.5% protection of the cells). Regarding the acyclovir-resistant mutant HSV-2 strain PU and wild-type HSV-2 strain Bja, the antiviral activity and selectivity of the extract were very low, with EC50 values from 0.1 to 0.01 mg/mL, and the selectivity index ranging from 25 to 250, respectively. The GP extract exhibited selective inhibitory activity also on the growth of Gram-positive bacterial pathogens, with Staphylococcus aureus being most sensitive. It also prevented the formation of MRSA biofilm up to 50% at a concentration of 1.6 mg/mL and up to 90% at a concentration of 2.5 mg/mL. The anti-herpetic and antibacterial activities demonstrated in our investigation are probably related to the presence of phenols, and in particular gallic acid. The antimicrobial activity of the GP extract holds a promise for the future development of nutrition supplements based on G. paraguayense and therefore warrants further studies aimed at isolating biologically active compounds or mixtures thereof with subsequent in-depth investigation of their anti-HSV and antibacterial mechanisms of action.

Houttuynoid M, an Anti-HSV Active Houttuynoid from Houttuynia cordata Featuring a Bis-houttuynin Chain Tethered to a Flavonoid Core.

Houttuynoid M (1), a new houttuynoid, and the related known compound houttuynoid A (2) were isolated from Houttuynia cordata. Their structures were defined using NMR data analysis, HR-MSn experiment, and chemical derivatization. Houttuynoid M is the first example of a houttuynoid with a bis-houttuynin chain tethered to a flavonoid core. A putative biosynthetic pathway of houttuynoid M (1) is proposed. The anti-herpes simplex virus (anti-HSV) activities of 1 and 2 (IC50 values of 17.72 and 12.42 μM, respectively) were evaluated using a plaque formation assay with acyclovir as the positive control.

Casuarinin effects on cancer chemoprevention: Progress, potential and promise

Casuarinin is tannin with many medicinal properties. It has antiproliferative, antioxidant, Anti herpes simplex virus (HSV) activity and anticancer activity. Anticancer activity of Casuarinin has been proven in breast cancer, non-small lung cancer, oral tumor and leukemia by different experiments. However further work is required to establish how this tannin system can be best manipulated for therapeutic benefit. This review focuses on the use of this tannin as a medicine for cancer treatment.

Evaluation of Biological Activity of Mastic Extracts Based on Chemotherapeutic Indices.

Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by β-hydroxylation of testosterone. Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4. Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic.

Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine

ObjectiveTo evaluate the monogalactosyl diglyceride (MGDG) and digalactosyl diglyceride (DGDG) from Clinacanthus nutans (C. nutans) for their in vitro antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay. MethodsMGDG and DGDG were extracted with chloroform from C. nutans leaves. MGDG and DGDG were separated from chloroform crude extract using column chromatography, characterized by thin layer chromatography and quantified by high performance liquid chromatography. The anti HSV-1 and 2 activity against pre-treatment and post-treatment of the compounds was evaluated using plaque reduction assay. The cytotoxicity of the extract and the compounds on Vero cells were performed by MTT assay. ResultsMGDG and DGDG obtained by column chromatography showed identical profiles as standard MGDG and standard DGDG using thin layer chromatography and high performance liquid chromatography. MGDG and DGDG from C. nutans showed 100% inhibition of HSV-1 replication at the post step of infection at noncytotoxic concentration with IC50 values of 36.00 and 40.00 μg/mL, and HSV-2 at 41.00 and 43.20 μg/mL, respectively. Moreover, MGDG and DGDG from C. nutans were demonstrated to have anti-herpes simplex activity at the same level as standard synthetic compounds. In contrast, pre-treatment of Vero cells with MGDG and DGDG before HSV-1 and HSV-2 infection did not show inhibitory effect against these viruses. MGDG and DGDG exhibited antiviral activity against HSV-1 with selectivity index of 26.00 and 23.00 and HSV-2 of 23.30 and 21.30. ConclusionsMGDG and DGDG from C. nutans, a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2, probably by inhibiting the late stage of multiplication, suggesting their promising use as anti-HSV agents.

Synthesis of multi ring-fused imidazo [1,2- a]isoquinoline-based fluorescent scaffold as anti-Herpetic agent.

Natural product-inspired synthesis is a key incorporation in modern diversity-oriented synthesis to yield biologically novel scaffold. Inspired by β-carboline fused system, we have designed molecules with multi ring fused scaffold by modifying the tricyclic pyrido[3,4- b]indole ring with imidazo[1,2- a]isoquinoline. A highly convergent approach with new C-N and C-C bond formation to synthesize multiring fused complex scaffold imidazo[1,2- a]isoquinolinies as fluorophores. N-nucleophile-induced ring transformation of 2 H-pyran-2-one followed by in situ cis-stilbene-type oxidative photocyclization yielded new C-C bond formation without additional oxidant. The cytotoxicity, effective concentrations, and the mode of action of the synthesized analogs were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),, plaque reduction, time of addition, and reverse transcriptase Polymerase Chain Reaction (PCR). Novel imidazo[1,2- a]isoquinoline analogs were prepared, and the results revealed that trans isomer of cyclopropyl analog (EC50 35 and 37.5 µg/ml) and trans isomer of citric acid salt of phenyl analog (EC50 38.2 and 39.8 µg/ml) possess significant anti-Herpes Simplex Virus (HSV) activity with selectivity index of >10. The kinetic study demonstrated that both the analogs inhibited HSV-1F and HSV-2G at 2-4 h postinfection. Finally, western blot and reverse transcriptase PCR assays revealed that both the analogs suppressed viral immediate early transcription. Novel imidazo[1,2- a]isoquinoline analogs were synthesized from pyranone with appropriate amines. Two compounds showed better antiviral profile on HSV-infected Vero cells, compared to the standard drug acyclovir (ACV). Overall, we discovered a promising scaffold to develop a nonnucleoside lead targeting the viral immediate early transcription for the management of HSV infections.

Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae

Acyclovir is a commonly-used drug for treating herpes simplex virus (HSV) infections, but with its wide clinical application, more and more resistant strains have been found. Therefore, seeking a drug that can act against acyclovir-resistant virus has become an important goal of drug screening and development. In this study, plaque reduction assay, real-time PCR, Western blot, and immunofluorescence technique were used to investigate the antiviral effect of Eucheuma gelatinae polysaccharide (EGP) on HSV and to preliminarily clarify the in vitro anti-HSV mechanism of EGP. EGP was found to significantly inhibit HSV infection in vitro and displayed a good inhibitory effect on acyclovir-resistant strains. More detailed experiments have shown that EGP prevented early HSV-1 infection through directly inactivating HSV-1 particles and impairing virus attachment, but without effect on viral penetration. EGP also inhibited the RNA synthesis of HSV-1 early gene and late gene as well as viral DNA replication; no effect on immediate-early gene synthesis was observed. Besides, through immunofluorescence and western blot, we found that EGP significantly affected the protein synthesis of HSV-1. Taken together, these results demonstrate that EGP exerts its anti-HSV activity mainly through impeding early HSV-1 infection and inhibiting viral RNA and DNA syntheses. The weak cytotoxicity, strong viral inactivation as well as attachment inhibition activity enable EGP to be a virucide candidate for HSV therapy, especially for drug-resistant strains.

Stereoselective synthesis of 4'-selenonucleosides via seleno-Michael reaction as potent antiviral agents.

Based on the hypothesis that the bulky selenium atom, with 4p orbitals, can sterically hinder the approach of a cellular kinase to 5'-OH for phosphorylation, 4'-selenonucleosides with one-carbon homologation were designed and synthesized via a novel seleno-Michael reaction, with the stereoselectivity controlled by steric effects. 5'-Homo-4'-selenonucleosides (n = 2) demonstrated potent antiherpes simplex virus (HSV-1) activity, indicating that the bulky selenium atom might play a key role in preventing phosphorylation by cellular kinases, resulting in no antiviral activity.

Antiherpetic Mechanism of a Sulfated Derivative of Agaricus brasiliensis Fruiting Bodies Polysaccharide

Objective: To study the anti-herpes simplex virus (HSV) activity of a (1→6)-(1→3)-β-<smlcap>D</smlcap>-glucan isolated from Agaricus brasiliensis fruiting bodies (FR) as well as its chemically sulfated derivative (FR-S). Methods: The antiherpetic activity and mechanism of action was studied by viral plaque assay applying different methodological strategies. Results: Although FR presented no in vitro antiherpetic action at 1 mg/ml, FR-S displayed promising anti-HSV-1 and anti-HSV-2 activities in both simultaneous and postinfection treatments, resulting in selectivity indices (CC₅₀/EC₅₀) higher than 393. FR-S had no virucidal effect, but significantly suppressed HSV-1 (EC₅₀ = 0.32 µg/ml) and HSV-2 (EC₅₀ = 0.10 µg/ml) adsorption. FR-S was less effective on adsorption inhibition of mutant virus strains devoid of gC (HSV-1 gC^-39 and HSV-2 gCneg1), indicating a possible interaction with this glycoprotein. The reduction of viral adsorption upon cell pretreatment with FR-S also suggests its interaction with cellular components. FR-S inhibited HSV-1 (EC₅₀ = 8.39 µg/ml) and HSV-2 (EC₅₀ = 2.86 µg/ml) penetration more efficiently than heparin. FR-S reduced HSV-1 and HSV-2 cell-to-cell spread. A synergic effect between FR-S and acyclovir was also detected. Conclusions: FR-S displays an interesting mechanism of antiviral action and represents a promising candidate for the treatment and/or prevention of herpetic infections, to be used as a single therapeutic agent or in combination with acyclovir.

Inhibitory effect of aromatic herbs, lavender, sage and chamomile against herpes simplex virus infection

This study demonstrated anti-herpes simplex virus (HSV) activity of lavender, sage and chamomile extracts. Green monkey kidney cells were protected from HSV-2 infection by dichloromethane and methanol extract of lavender with therapeutic indices (TI) of 1.98 and 2.90, respectively when the cells were treated before viral infection. Moreover, the dichloromethane extract of chamomile showed the highest TI which was 20.74 against HSV-1 when the virus was treated during adsorption. The inhibitory effect of dichloromethane extract of lavender significantly had the highest TI (45.90) when HSV-1 was treated after viral adsorption. The highest inhibitory effect against HSV-2 was observed after treatment of the virus with methanol and dichloromethane extracts of sage, with TIs of 9.02 and 10.1, respectively. Chamomile extracts showed significant virucidal effects on both HSV-1 and HSV-2 viral particles. The inhibitory effect of chamomile extracts on HSV-1 and HSV-2 viral yield after viral replication was the highest at 30 h after treatment. Respective reductions of viral titers by 9.7 and 7.1 fold were observed when cells were treated with dichloromethane and methanol extract of chamomile. Therefore, chamomile, sage and lavender were demonstrated to possess anti-herpes simplex virus activities at various stages of the viral multiplication cycle. Key words : Chamomile, sage, lavender, herpes simplex virus (HSV), anti-herpes simplex virus.

Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice

Anti-herpes simplex virus (HSV) activities of oxyresveratrol in vitro and topical administration in cutaneous HSV-1 infection in mice were examined. The inhibitory concentrations for 50% plaque formation (IC 50) of oxyresveratrol against HSV-1 clinical isolates and HSV-2 clinical isolates were 20.9–29.5 and 22.2–27.5 μg/ml, respectively. In topical administration in cutaneous HSV-1 infection in mice, 2.5%, 5%, 10% and 20% oxyresveratrol in cream vehicle applied three times daily for 7 days after infection were evaluated and 10% and 20% oxyresveratrol cream were significantly effective in delaying the development of skin lesions and protection from death ( P < 0.01). The concentration of 10% oxyresveratrol in cream was significantly more effective than that of 30% oxyresveratrol in vaseline applied three times daily ( P < 0.01). Oxyresveratrol cream at 20% was as effective as 5% ACV cream applied three times daily ( P < 0.01). Both 10% and 20% oxyresveratrol cream were as effective as that of 5% ACV cream applied two times daily ( P > 0.05). Therapeutic efficacy of oxyresveratrol in cream vehicle was dose-dependent and the maximum efficacy observed on day 6 after infection was shown at 10% oxyresveratrol in cream applied three times daily. The frequency of application of 10% oxyresveratrol cream at three, four and five times daily was as effective as that of 5% ACV cream applied five times daily ( P > 0.05). These results demonstrated that topical administration of oxyresveratrol in novel cream vehicle reduced the concentration of oxyresveratrol to 10% and was suitable for cutaneous HSV infection.

Polyphenols including catechin from green tea with in vitro antiviral activity exhibited anti-herpes simplex virus activity but not anti-influenza virus activity in mice

Polyphenols including catechin from green tea with in vitro antiviral activity exhibited anti-herpes simplex virus activity but not anti-influenza virus activity in mice

Synthesis and Antiviral Activity of Novel 1,3,4-Thiadiazine Derivatives

A series of novel 1,3,4-thiadiazine derivatives were synthesized via chemical optimization on phthiobuzone. Their anti-herpes simplex virus (HSV) activities in vitro were also tested. Several compounds exhibited more highly potent anti-HSV activity and much higher selectivity index (SI) values than those of phthiobuzone. The most potent anti-HSV compound was 4f, which showed marked inhibition against HSV-1 (IC₅₀=77.04 µg/ml) and HSV-2 (IC₅₀=30.00 µg/ml). Meanwhile it had low cytotoxicity (CC₅₀=1000.00 µg/ml), resulting in high (SI(HSV-1)=12.98, SI(HSV-2)=33.33, respectively). Furthermore, a computational study for prediction of absorption, distribution, metabolism, excretion (ADME) properties of compound 4f was performed by determination of topological polar surface area, absorption and Lipinski parameters.