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Biologically active phytochemicals from pumpkin reveal versatile medical applications, though little is known about their antiviral activity. The fucose-rich polysaccharide extraction conditions were optimized through Box-Behnken design and purified by column chromatography. The purified fucose-rich polysaccharide was characterized through SEM, FT-IR, 1 H NMR, XRD, TGA, and GS-MS. The analysis results revealed an irregular and porous surface of the purified polysaccharide with high fucose, rhamnose, galactose, and glucose contents. The tested fucose-rich polysaccharides revealed significant antioxidant and anti-inflammatory activity at very low concentrations. The purified fucose-rich polysaccharides exerted a broad-spectrum antiviral activity against both DNA and RNA viruses, accompanied by high safety toward normal cells, where the maximum safe doses (EC 100 ) were estimated to be about 3-3.9 mg/mL for both Vero and PBMC cell lines. Treatment of HCV, ADV7, HSV1, and HIV viruses with the purified polysaccharides showed a potent dose-dependent inhibitory activity with IC 50 values of 95.475, 20.96, 5.213, and 461.75 μg/mL, respectively. This activity was hypothesized to be through inhibiting the viral entry in HCV infection and inhibiting the reverse transcriptase activity in HIV. The current study firstly reported the antioxidant, anti-inflammatory, and antiviral activities of Cucurbita maxima fucose-rich polysaccharide against several viral infections., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) ( 1 ) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several classes of derivatives were synthesized. The synthesized compounds were characterized by 1H NMR, IR, UV, and mass spectrometry. In addition, several of the synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single round infection assay using TZM-bl cells at 100 ng/mL. TFV ( 1 ) was used as a positive control and inhibited HIV infection by 35%. Among all the evaluated compounds, the disubstituted heptanolyl ester alanine phosphonamidate with naphthol oleate ( 69 ), pentanolyl ester alanine phosphonamidate with phenol oleate ( 62 ), and butanolyl ester alanine phosphonamidate with naphthol oleate ( 87 ) ester conjugates of TFV were more potent than parent drug TFV with 79.0%, 76.5%, 71.5% inhibition, respectively, at 100 ng/mL. Furthermore, two fatty acyl amide conjugates of tenofovir alafenamide (TAF) were synthesized and evaluated for comparative studies with TAF and TFV conjugates. Tetradecanoyl TAF conjugate 95 inhibited HIV infection by 99.6% at 100 ng/mL and showed comparable activity to TAF (97-99% inhibition) at 10-100 ng/mL but was more potent than TAF when compared at molar concentration.

Background: In many resource-poor settings such as Peru, children affected by HIV have a high prevalence of neurodevelopmental delays (NDDs) and remain excluded from adequate treatment., Methods: Community health workers (CHWs) administered NDD screening instruments to assess child development and associated caregiver and household factors in 14 HIV-affected parent-child dyads. Focus group discussion with caregivers was conducted to explore their needs and behaviors around early child stimulation and to assess their perceptions of the screening experience., Results: Over 70% of the children had abnormal classification in at least 1 (out of 5) developmental domains according to Ages and States Questionnaire-provided cutoff scores. Caregiver depression and stress were associated with abnormal development as were some parenting behavior factors. Knowledge about child development was low. Caregivers felt testing and discussing results with a CHW were very insightful. Reported caregiver behavior differed between caregivers with HIV-infected children and those with uninfected children., Conclusion: Taken together, these exploratory quantitative data suggest that parenting behaviors associated with low child development scores may be modifiable and that community-based testing is well received and informative to these HIV-infected caregivers.

The first Colombian to claim a judicially enforceable right to health was a gay man living with HIV, who in 1992 claimed a violation of his constitutional rights on account of being denied antiretroviral therapy. Since then, HIV activists have been at the forefront of advancing both the judicialization and social reconstruction of health as a human right. However, their role-and its implications today-has been sometimes overlooked in the study of Colombia's right to health. Based on semi-structured interviews with key stakeholders, we evaluate the HIV movement's effect on the progression of the right to health and resulting health care reform, and analyze the reform's success in addressing the needs of people living with HIV. While the landmark Constitutional Court decision T-760 and resulting health care reform are not the result of any one group, the HIV movement played a significant role in these developments, and its values are largely reflected in the country's new sociopolitical conceptualization of the right to health. However, the movement has faced division over the issue of generic medication availability and among subpopulations who have not been strongly represented or consistent beneficiaries of its successes., Competing Interests: Competing interests: None declared.

Objective: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with average survival of less than 3 years if left untreated. It is most common in patients infected with HIV. Although the pathogenesis in this population is not fully understood, it is thought that HIV infection, through the immune response and release of different inflammatory mediators such as endothelin-1, may contribute directly to endothelial damage. Our objective was to quantify endothelin-1 levels in HIV-infected patients and determine whether or not there is an association between this marker and PAH., Design: A case-control study in patients attending an infectious diseases clinic., Methods: The sample was composed of 79 patients divided into three groups: 23 HIV patients with PAH (HIV+/PAH+), 45 HIV patients without PAH (HIV+/PAH-) and a control group of 11 healthy individuals. The ratio between the HIV+/PAH- and HIV+/PAH+ groups was 2 : 1. Patients were matched by age, sex, risk group and viral load; the control group by age and sex. All patients had blood taken for endothelin-1 plasma quantification., Results: We found lower endothelin-1 levels in the controls than in the HIV+/PAH- group [0.71 pg/ml (interquartile range, IQR 0.54-0.94) vs. 1.13 pg/ml (IQR 0.87-1.38); P = 0.005] and the HIV+/PAH+ cohort [1.16 pg/ml (IQR 0.86-2.37); P = 0.003]. Patients with severe PAH had higher endothelin-1 levels [2.94 pg/ml (IQR 1.81-6.33)] than patients with mild and moderate PAH., Conclusion: Plasma endothelin-1 levels are higher in HIV patients with PAH than in the HIV-noninfected population and levels increase with the severity of the PAH.