An in silico investigation of phytochemicals as potential inhibitors against non-structural protein 1 from dengue virus 4

Dengue fever has emerged as a big threat to human health since the last decade owing to high morbidity with considerable mortalities. The proposed study aims at the in silico investigation of the inhibitory action against DENV4-NS1 of phytochemicals from two local medicinal plants of Pakistan. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. A total of 129 phytochemicals (50 from Tanacetum parthenium and 79 from Silybum marianum) were selected for this study. The tertiary structure of DENV4-NS1 was predicted based on homology modelling using Modeller 9.18 and the structural stability was evaluated using molecular dynamics simulations. Absorption, distribution, metabolism, excretion and toxicity (ADMET) along with the drug-likeness was also predicted for these phytochemicals using SwissADME and PreADMET servers. The results of ADMET and drug-likeness predictions exhibited that 54 phytochemicals i.e. 25 from Tanacetum parthenium and 29 from Silybum marianum showed effective druglikeness. These phytochemicals were docked against DENV4-NS1 using AutoDock Vina and 18 most suitable phytochemicals with binding affinities ≤ -6.0 kcal/mol were selected as potential inhibitors for DENV4-NS1. Proposed study also exploits the novel inhibitory action of Jaceidin, Centaureidin, Artecanin, Secotanaparthenolide, Artematin, Schizolaenone B, Isopomiferin, 6, 8-Diprenyleriodictyol, and Anthraxin against dengue virus. It is concluded that the screened 18 phytochemicals have strong inhibition potential against Dengue Virus 4.

Weekly azathioprine pulse versus daily azathioprinein the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study.

Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP) are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the effi cacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically signifi cant and comparable (P = 0.366). Patients on WAP had a higher incidence of adverse effects (P = 0.02). Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

Parthenium dermatitis treated with azathioprine weekly pulse doses.

BACKGROUND: Parthenium dermatitis is a serious problem in India. Corticosteroids are the mainstay of treatment but the prolonged use of corticosteroids can cause serious side effects. Azathioprine used in daily doses has been shown to be effective. AIM: We have evaluated the effectiveness of azathioprine weekly pulse doses for the treatment of parthenium dermatitis. METHODS: Twelve patients, ten males and two females, aged between 39 and 65 years (mean +/- SD = 53.5 +/- 8.7) having air-borne contact dermatitis to Parthenium hysterophorus for 3-19 years (mean = 6.33) were included in the study. The diagnosis in each patient was confirmed by patch-testing. The severity of the disease was determined by clinical severity score (CSS) on the basis of erythema, itching, type of lesions, and areas of body involved. RESULTS: The pretreatment CSS in these patients varied from 29.7 to 55.5 (mean +/- SD: 40.40 +/- 7.95). After clinical and laboratory evaluation, the patients were treated with 300-mg azathioprine once-weekly doses for 6 months. Clinical and laboratory evaluations were repeated at weeks 1, 2, and then every 4 weeks until the end of therapy to evaluate the therapeutic response and side effects. The response was excellent (80-100% clearance of disease) in seven (58.33%) patients and good (60% clearance) in five (41.66%) patients. The post-treatment CSS decreased from the mean +/- SD of 40.4 +/- 7.95 to 10.9 +/- 8.43 (P = 0.002). There were no significant side effects of the therapy. CONCLUSIONS: In this preliminary open study, azathioprine in weekly pulse doses has been found to be effective without any serious adverse effects in the treatment of parthenium dermatitis. The cost of therapy with this regimen is reduced by 60%.

Exposure to Parthenium hysterophorous pollen extract leads to bronchospasm in stable patients of bronchial asthma.

Role of Parthenium hysterophorous as an allergen evoking bronchial hyper-responsiveness was assessed in twenty five adult patients with stable asthma and ten healthy controls. Assessment was made with the help of skin prick and bronchial provocation tests (BPT) using a commercially available Pathenium extract. Eleven patients (44%) of the study group had a positive skin reaction and 4 (16%) showed a significant fall in FEV1 and PEFR (p < 0.05) on bronchial provocation. In the control group only one patient (10%) had a positive skin test while there was none with a positive bronchial challenge. There was a significant fall in the mean values of FEV1 and PEFR over base line after the BPT in patients of asthma than controls. It is concluded that a significant proportion of bronchial asthma patients are sensitized to Parthenium hysterophorous and it may act as a cofactor in seasonal exacerbation of their symptoms.