To study the in-vivo efficacy and safety of AYUSH polyherbal formulation among COVID-19 infected Syrian gold hamsters

The COVID-19 pandemic has infected millions of people around the world and the resulting disease burden has challenged the already stressed healthcare systems globally. Amidst the increasing morbidity rate of SARS-CoV-2, the scientific community is vigorously researching possible remedies targeted against the virus. Natural herbs have a great potency to cure infectious diseases and are vastly unexplored. The present study aims to investigate Ayurvedic herbs in a unique polyherbal formulation, NOQ19, against the SARS-CoV-2 virus in an animal model. A total of 19 female Syrian hamsters were infected with the virus cell culture through intranasal route. 4 out of 19 animals were mock controls, 5 were infection controls, 4 were treated with remdesivir and acted as positive controls and remaining 6 were treated with NOQ19. The hamsters were observed to note body weight reduction and adverse events followed by sacrifice on day 4 after inoculation with the virus. The lung pathology and viral load was studied in each hamster. Results showed a significant reduction of 78.2% in the viral load for the NOQ19 arm, as compared to the infection control. Gross examination of the lung histology of the NOQ19 arm suggested an improvement in edema and congestion compared to the infection control. Also, no adverse events were noticed in NOQ19 hamster group. Therefore, the authors propose NOQ19 formulation as a potential option to be tested further for its efficacy and efficiency against COVID-19.

EVALUATION OF A PEDIATRIC LIQUID FORMULATION TO IMPROVE 6-MERCAPTOPURINE THERAPY IN CHILDREN

Background6-mercaptopurine (6-MP), a key drug for treatment of acute lymphoblastic leukemia (ALL), has until recently had no adequate formulation for pediatric patients. Several approaches have been taken but the only oral paraben-free 6-MP liquid formulation named Loulla was developed and evaluated in the target population. Preclinical and clinical evaluation was performed according to a Pediatric Investigation Plan, in order to apply for a Pediatric Use Marketing Authorization.MethodsThe pre-clinical study assessed the maximum tolerated dosage-volume and evaluated local mucosal toxicity of 28 daily administrations in treated compared to controls gold hamsters. The multi-centre clinical study was single-dose, open-label, crossover trial, conducted in 15 ALL children during maintenance therapy. The bioavailability and palatability of a single 50 mg fixed dose of Loulla compared to 50 mg registered tablets were evaluated in a random order on two consecutive days. Seven blood samples over 9 hours were obtained each day at to determine 6-MP pharmacokinetic parameters, including Tmax, Cmax, AUC0–9 and AUC0–∞. A questionnaire adapted to children testing Loulla palatability and preference for either Loulla or the usual 6-MP tablet was completed. Occurrence of adverse events was determined at study visits by vital sign measurements, patient's spontaneous reporting, investigator's questioning and clinical examination.ResultsThe preclinical study in gold hamsters showed that dosage-volume of 75 mg/kg/day was well tolerated. The relative bioavailability of liquid Loulla formulation compared to the reference presentation is 76% for AUC0-9 and AUC0-∞ and 80% for Cmax. The taste of Loulla and the mouth feeling after ingestion compare favorably to the tablet. No adverse event occurred.ConclusionPharmacokinetic, palatability and safety data support the use of Loulla in children.

SV40-transformed hamster cells resistant to 100–250 microgram/ml of ethidium bromide

SV40-transformed hamster cells were selected for resistance to ethidium bromide (EB). Several cell lines were established, which grew in the presence of up to 250 microgram/ml EB. The EB resistance is genetically stable. The cloned resistant cells show no difference in morphology, with the exception of the mitochondrial ultrastructure, which exhibits condensed cristae formation. The tumorigenicity of these cells in Syrian gold hamsters is considerably reduced. Incorporation of radioactive labelled thymidine into mitochondrial DNA is not influenced by the presence of the drug. Gel electrophoresis with mitochondrial proteins from wild-type and resistant cells reveals significantly different patterns. The mechanism of EB resistance is discussed.