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The challenges of viral infection have increased in recent decades due to the emergence of resistance, crossresistance and drying up of antiviral drug discovery. Many neglected tropical viruses including the chikungunya virus,
dengue virus & Japanese encephalitis virus have gradually become global pathogens. This has further increased the
burden of viral infection which necessitates the continuous development of antiviral therapy. The antiviral chemistry
began with the development of thiosemicarbazide derived thiosemicarbazones as antiviral. Although very few
thiosemicarbazides have progressed into clinical application, it still inspires antiviral development. During last 3 decades
(1990-2020), several efforts have been made to develop suitable antiviral by using thiosemicarbazide scaffold. Its
hybridization with other pharmacophores has been used as a strategy to enhance safety and efficacy. Cyclization and
substitution of thiosemicarbazides have also been used to develop potent antiviral. With the ability to form coordinate
bonds, thiosemicarbazides have been used either as metal complex or chelator against viruses. This work is an attempt to
systematically review the research on the use of thiosemicarbazides as an antiviral scaffold. It also reviews the structureactivity relationship and translational suitability of thiosemicarbazide derived compounds.
Introduction
The emergence of drug resistance and cross-resistance to existing drugs has warranted the development of new antivirals for Herpes simplex viruses (HSV). Hence, we have designed this study to evaluate the anti-viral activity of 1-[(2-methyl benzimidazole-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT), against HSV-1.
Method
Molecular docking was performed to assess the affinity of MBZM-N-IBT for HSV-1 targets. This was validated by plaque assay, estimation of RNA and protein levels as well as time of addition experiments in vitro.
Result
Molecular docking analysis suggested the inhibitory capacity of MBZM-N-IBT against HSV-1. This was supported by the abrogation of the HSV-1 infectious viral particle formation with the IC50 value of 3.619 µM. Viral mRNA levels were also reduced by 72% and 84% for UL9 and gC respectively. MBZM-N-IBT also reduced the protein synthesis for gC and ICP8 significantly. While mRNA of ICP8 was not significantly affected, its protein synthesis was reduced by 47%. The time of addition experiment revealed the capacity of MBZM-N-IBT to inhibit HSV-1 at early as well as late stages of infection in the Vero cells. Similar effect of MBZM-N-IBT was also noticed in the Raw 264.7 and BHK 21 cells after HSV-1 infection. Supported by the in silico data, this can be attributed to possible interference with multiple HSV targets including the ICP8, ICP27, UL42, UL25, UL15 and gB proteins.
Conclusion
These results along with the lack of acute oral toxicity and significant anti-inflammatory effects suggest its suitability for further evaluation as a non-nucleoside inhibitor of HSV.
The main objective of the study was to develop orodispersible tablets of Granisetron hydrochloride, a selective 5-HT3 receptor antagonist (an antivomiting agent) for improving patient compliance, especially those of paediatric & geriatric categories with difficulties in swallowing. In the wet granulation method orodispersible (ORD) tablets were prepared using natural super disintegrants plantago ovate.The prepared batches of tablets were evaluated for weight variation, hardness, friability, wetting time, in vitro dispersion time, drug content and in vitro dissolution studies. The tablet formulation batch F4 was considered as the overall best formulation (with an in vitro drug release study of 99.11%).Short term stability studies (at 40±2ºC/75±5% RH) on the best formulation indicated that there no significant changes in drug content. From the Fourier Transform Infrared (FTIR) spectroscopy study indicated that there are no drug excipient interactions.
Aspirin (ASA) has been utilized against many inflammatory disorders. In recent years a growing body of research also suggests its efficacy against cancer. The use of ASA in these conditions requires long-term treatment. However, gastro-toxicity associated with ASA is a major challenge. Household species including turmeric, ginger, and cinnamon have enjoyed medicinal values including gastroprotective properties. Accordingly, their co-use with ASA may be beneficial in ensuring a safe long-term treatment. With this objective, the study was undertaken which revealed encouraging effects. A positive interaction was found with analgesic effect and anti-inflammatory effect of ASA. Further, these spices were shown to prevent gastro toxicity of ASA. In conclusion, ginger and turmeric can be used to complement the use of ASA against inflammatory disorders without the deleterious effects on stomach mucosa.
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