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Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection.

ABSTRACT: Herpes simplex virus-2 (HSV-2) infection is the most common cause of genital ulcers. The impact of ulcers also demonstrates a strong link to the human immunodeficiency virus (HIV) infection. Complications, drug resistance, and side-effects of anti-viral drugs make the treatment of HSV-2 infection challenging. Herbal medicines have shown potential against HSV-2 and HIV infections. In this context, polyherbal gel formulation comprising 50% ethanolic extracts from Acacia catechu, Lagerstroemia speciosa, Terminalia chebula and Phyllanthus emblica has been developed. The gel formulation significantly exhibited virucidal activity against both HIV-1 and HSV-2 infections with IC50, 55.93 ± 5.30 µg/mL and 27.26 ± 4.87 µg/mL, respectively. It also inhibited HSV-2 attachment and penetration to the Vero cells with an IC50 = 46.55 ± 1.25 µg/mL and 54.94 ± 2.52 µg/mL respectively, which were significantly lower than acyclovir. However, acyclovir is more potent in post-infection assay with an IC50 = 0.065 ± 0.01 µg/mL whereas gel formulation showed an IC50 = 469.05 ± 16.65 µg/mL under similar conditions. Gel formulation showed no inhibitory effect on the viability of lactobacilli, human vaginal keratinocyte cells (Vk2/E6E7), and the integrity of the Caco-2 cells monolayer. Gel formulation did not lead to any significant increase in the secretion of pro-inflammatory cytokines and mutagenic index. The proposed gel formulation may be a promising candidate microbicide for the prevention of sexually transmitted HIV-1 and HSV-2.

SUBMITTER: Mishra NN

PROVIDER: S-EPMC6266149 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection.

Mishra Nripendra Nath NN Kesharwani Ajay A Agarwal Aakanksha A Polachira Suja Kizhiyedath SK Nair Reshmi R Gupta Satish Kumar SK

Viruses 20181024 11

Herpes simplex virus-2 (HSV-2) infection is the most common cause of genital ulcers. The impact of ulcers also demonstrates a strong link to the human immunodeficiency virus (HIV) infection. Complications, drug resistance, and side-effects of anti-viral drugs make the treatment of HSV-2 infection challenging. Herbal medicines have shown potential against HSV-2 and HIV infections. In this context, polyherbal gel formulation comprising 50% ethanolic extracts from <i>Acacia catechu</i>, <i>Lagerstr ...[more]

PMID: 30352961

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Project description:BACKGROUND:Early diagnosis of human immunodeficiency virus (HIV) is important because antiretroviral therapies are more effective if infected individuals are diagnosed early. Diagnosis of HIV relies on laboratory testing and determining the demographic and clinical characteristics of undiagnosed HIV-infected patients may be useful in identifying patients for testing. This systematic review aims to identify characteristics of HIV-infected adults prior to diagnosis that could be used in a prediction model for early detection of patients for HIV testing in UK primary care. METHODS:The population of interest was adults aged ??18 years in developed countries. The exposures were demographic, socio-economic or clinical characteristics associated with the outcome, laboratory confirmed HIV/AIDS infection. Observational studies with a comparator group were included in the systematic review. Electronic searches for articles from January 1995 to April 2016 were conducted on online databases of EMBASE, MEDLINE, The Cochrane Library and grey literature. Two reviewers selected studies for inclusion. A checklist was developed for quality assessment, and a data extraction form was created to collate data from selected studies. RESULTS:Full-text screening of 429 articles identified 17 cohort and case-control studies, from 26,819 retrieved articles. Demographic and socio-economic characteristics associated with HIV infection included age, gender and measures of deprivation. Lifestyle choices identified were drug use, binge-drinking, number of lifetime partners and having a partner with risky behaviour. Eighteen clinical features and comorbid conditions identified in this systematic review are included in the 51 conditions listed in the British HIV Association guidelines. Additional clinical features and comorbid conditions identified but not specified in the guidelines included hyperlipidemia, hypertension, minor trauma and diabetes. CONCLUSION:This systematic review consolidates existing scientific evidence on characteristics of HIV-infected individuals that could be used to inform decision making in prognostic model development. Further exploration of availability of some of the demographic and behavioural predictors of HIV, such as ethnicity, number of lifetime partners and partner characteristics, in primary care records will be required to determine whether they can be applied in the prediction model.

Project description:Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens, in particular herpes simplex virus type 2 (HSV-2). The resulting coinfection is involved in a vicious circle of mutual facilitations. Therefore, an important task is to develop a compound that is highly potent against both viruses to suppress their transmission and replication. Here, we report on the discovery of such a compound, designated PMEO-DAPym. We compared its properties with those of the structurally related and clinically used acyclic nucleoside phosphonates (ANPs) tenofovir and adefovir. We demonstrated the potent anti-HIV and -HSV activity of this drug in a diverse set of clinically relevant in vitro, ex vivo, and in vivo systems including (i) CD4⁺ T-lymphocyte (CEM) cell cultures, (ii) embryonic lung (HEL) cell cultures, (iii) organotypic epithelial raft cultures of primary human keratinocytes (PHKs), (iv) primary human monocyte/macrophage (M/M) cell cultures, (v) human ex vivo lymphoid tissue, and (vi) athymic nude mice. Upon conversion to its diphosphate metabolite, PMEO-DAPym markedly inhibits both HIV-1 reverse transcriptase (RT) and HSV DNA polymerase. However, in striking contrast to tenofovir and adefovir, it also acts as an efficient immunomodulator, inducing β-chemokines in PBMC cultures, in particular the CCR5 agonists MIP-1β, MIP-1α and RANTES but not the CXCR4 agonist SDF-1, without the need to be intracellularly metabolized. Such specific β-chemokine upregulation required new mRNA synthesis. The upregulation of β-chemokines was shown to be associated with a pronounced downmodulation of the HIV-1 coreceptor CCR5 which may result in prevention of HIV entry. PMEO-DAPym belongs conceptually to a new class of efficient multitargeted antivirals for concomitant dual-viral (HSV/HIV) infection therapy through inhibition of virus-specific pathways (i.e. the viral polymerases) and HIV transmission prevention through interference with host pathways (i.e. CCR5 receptor down regulation).

Project description:HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS.We quantified antibodies that bind to the surface of whole Group B Streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants. Antibody-mediated complement C3b/iC3b deposition onto GBS of these serotypes was also quantified by a novel flow cytometry assay.Geometric mean concentration (GMC) of both surface-binding anti-GBS antibody and antibody-mediated complement deposition onto GBS were reduced in HIV-infected women (n=46) compared to HIV-uninfected women (n=58) for ST1a (surface-binding: 19.3 vs 29.3; p=0.003; complement deposition: 2.9 vs 5.3 SU/mL; p=0.003), STIb (24.9 vs 47.6; p=0.003; 2.6 vs 4.9 SU/mL; p=0.003), STII (19.8 vs 50.0; p=0.001; 3.1 vs 6.2 SU/mL; p=0.001), STIII (27.8 vs 60.1; p=0.001; 2.8 vs 5.3 SU/mL; p=0.001) and STV (121.9 vs 185.6 SU/mL; p<0.001) and in their infants for STIa (complement deposition 9.4 vs 27.0 SU/mL; p=0.02), STIb (13.4 vs 24.5 SU/mL; p=0.02), STII (14.6 vs 42.7 SU/mL; p=0.03), STIII (26.6 vs 62.7 SU/mL; p=0.03) and STV (90.4 vs 165.8 SU/mL; p=0.04). Median transplacental transfer of antibody from HIV-infected women to their infants was reduced compared to HIV-uninfected women for GBS serotypes II (0.42 [IQR 0.22-0.59] vs 1.0 SU/mL [0.42-1.66]; p<0.001), III (0.54 [0.31-1.03] vs 0.95 SU/mL [0.42-3.05], p=0.05) and V (0.51 [0.28-0.79] vs 0.75 SU/mL [0.26-2.9], p=0.04). The differences between infants remained significant at 16 weeks of age.Maternal HIV infection was associated with lower anti-GBS surface binding antibody concentration and antibody-mediated C3b/iC3b deposition onto GBS bacteria of serotypes Ia, Ib, II, III and V. This may render these infants more susceptible to early and late onset GBS disease.

Dataset Information

Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection.

Publications

Herbal Gel Formulation Developed for Anti-Human Immunodeficiency Virus (HIV)-1 Activity Also Inhibits In Vitro HSV-2 Infection.

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