Effective Drug Candidates against Global Pandemic of Novel Corona Virus (nCoV-2019): A Probability Check through Computational Approach for Public Health Emergency.

The infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started form Wuhan, Chinais a devastating and the incidence rate has increased worldwide. Due to the lack of effective treatment against SARS-CoV-2, various strategies are being tested in China and throughout the world, including drug repurposing. To identify the potent clinical antiretroviral drug candidate against pandemic nCov-19 through computational tools. In this study, we used molecular modelling tool (molecular modelling and molecular dynamics) to identify commercially available drugs that could act on protease proteins of SARS-CoV-2. The result showed that Saquinavir, an antiretroviral medication can be used as a first line agent to treat SARS-CoV-2 infection. Saquinavir showed promising binding to the protease active site compared to other possible antiviral agents such as Nelfinavir and Lopinavir. Structural flexibility is one of the important physical properties that affect protein conformation and function and taking this account we performed molecular dynamics studies. Molecular dynamics studies and free energy calculations suggest that Saquinavir binds better to the COVID-19 protease compared to other known antiretrovirals. Our studies clearly propose repurposing of known protease inhibitors for the treatment of COVID-19 infection. Previously ritonavir and lopinavir were proved an important analogues for SARS and MERS in supressing these viruses. In this study it was found that saquinavir has exhibited good G-score and E-model score compared to other analogues. So saquinavir would be prescribe to cure for nCov-2019 either single drug or maybe in combination with ritonavir.

Pharmacophore model and atom-based 3D quantitative structure activity relationship (QSAR) of human immunodeficiency virus-1 (HIV-1) capsid assembly inhibitors.

A potential anti-Human Immunodeficiency Virus (HIV) agent with novel mode of action is urgently needed to fight against drug resistance HIV. The HIV capsid protein is important for both late and early stages of the viral replication cycle and emerged as a promising target for the developing of small molecule inhibitors of HIV. We design a Pharmacophore and 3D Quantitative structure activity relationship (QSAR) model for HIV Capsid Protein inhibitors, which helps to identify overall aspects of molecular structure that govern activity and for the prediction of novel HIV Capsid inhibitors. The hypothesis was developed with a survival score of 3.6.The features, that is, two aromatic rings, one hydrophobic site and two acceptor regions were present in all the active compounds with good fitness score. Pharmacophore model was then validated by a partial least square and regression-based PHASE 3D QSAR cross-validation. The leave-n-out cross validation for test set (Q2) of the hypothesis is 0.636, the standard deviation (SD) value is 0.338, and the variance ratio (F-test) value is 74.5. Hypothesis also showed a leave-n-out cross validation for training set (R2, 0.928). Interestingly, the predicted activity of true test set compounds was found in the close vicinity of their experimental activity suggesting the methodology used and models generated can be applied to identify potential new chemical entities with better HIV-1 capsid assembly inhibition.Communicated by Ramaswamy H. Sarma.

Understanding and implementing alternative solutions to address the COVID-19 pandemic in the sense of public health emergencies.

The Coronavirus disease (COVID-19) caused by the novel SARS-CoV-2 coronavirus has spread from China and quickly transmitted to most other countries around the world. The World Health Organization announced COVID-19 as a pandemic that is spreading steadily and soon in most states. Coronavirus genomic characterization showed that it most closely resembled another bat-origin beta-coronavirus. Coronavirus has the largest genome of viruses that have RNA. Spike (S) glycoprotein is present in the virus and is responsible for virus entry into the host cell. COVID-19 can spread through the droplet, direct contact, and aerosol transmission in humans. It can remain in the environment and exists on plastic and steel for the longest time, making it a dangerous and contagious disease that can kill other individuals. The virus has an incubation time of 2 to 14 days. Confirmed cases of COVID-19 have evolved exponentially in the world. Possible preventive steps for disease control include more mask use, hand sanitization, and social distancing. There is no antiviral therapy and only symptomatic care. Many inhibitors of HIV protease and other antimalarial drugs have tested. There is currently no vaccine available for COVID-19 prevention, though others are available in clinical trials. Scientists often use spike proteins for vaccine production. Research is needed to develop a new innovative vaccine and targeted medicine, which will meet people's demands.

A High-Performance Thin Layer Chromatography (HPTLC) Method for Simultaneous Determination of Diphenhydramine Hydrochloride and Naproxen Sodium in Tablets.

A rapid and simple high-performance thin layer chromatography (HPTLC) method with densitometry at 230 nm was developed and validated for simultaneous determination of diphenhydramine hydrochloride (DPH) and naproxen sodium (NPS) from pharmaceutical preparation. The separation was carried out on aluminum plates precoated with silica gel 60 F254 using mobile phase toluene:methanol:glacial acetic acid (7.5:1:0.2, v/v/v). The linearity range lies between 200 and 1200 ng/band for DPH and 1760 and 10,560 ng/band for NPS with correlation coefficients of 0.994 and 0.995, respectively. The R f value for DPH is 0.20 ± 0.05 and for NPS is 0.61 ± 0.06. % Recoveries of DPH and NPS was in the range of 99.70%-99.95% and 99.63%-99.95%, respectively. Limit of detection value for DPH was 13.21 ng/band and for NPS was 8.03 ng/band. Limit of quantitation value for DPH was 40.06 ng/band and for NPS was 24.34 ng/band. The developed method was validated as per ICH guidelines. In stability testing, DPH was found unstable to acid and alkaline hydrolysis, and DPH and NPS were found unstable to oxidation, whereas both the drugs were stable to neutral and photodegradation. The proposed method was successfully applied for the routine quantitative analysis of dosage form containing DPH and NPS.

Implementation of EPICS based vacuum control system for variable energy cyclotron centre, Kolkata.

The vacuum system of the Room Temperature (K = 130) Cyclotron of Variable Energy Cyclotron Centre is comprised of vacuum systems of main machine and Beam Transport System. The vacuum control system is upgraded to a PLC based Automated system from the initial relay based Manual system. The supervisory control of the vacuum system is implemented in Experimental Physics and Industrial Control System (EPICS). An EPICS embedded ARM based vacuum gauge controller is developed to mitigate the requirement of vendor specific gauge controller for gauges and also for seamless integration of the gauge controllers with the control system. A set of MS-Windows ActiveX components with embedded EPICS Channel Access interface are developed to build operator interfaces with less complex programming and to incorporate typical Windows feature, e.g., user authentication, file handling, better fonts, colors, mouse actions etc. into the operator interfaces. The control parameters, monitoring parameters, and system interlocks of the system are archived in MySQL based EPICS MySQL Archiver developed indigenously. In this paper, we describe the architecture, the implementation details, and the performance of the system.

Synthesis and pharmacological investigation of 3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates.

Fifteen new ethyl 6-methyl-2-methoxy-3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates (6a-o) have been synthesized in a two step reaction. In first step ethyl acetoacetate, s-methylisourea and appropriate benzaldehydes reacted in a single step reaction to obtain ethyl 6-methyl-2-methoxy-4-(substituted phenyl)-1, 4-dihydropyrimidine-5-carboxylates (4a-e). Second step involves synthesis of reaction between substituted phenacyl bromides and 1-4-dihydropyrimidine-5-carboxylates (6a-o). Their structures are confirmed by IR, (1)H NMR, mass and elemental analyses. The compounds were tested for antihypertensive activity by non-invasive tail-cuff, and evaluated by carotid artery cannulation method for determining the diastolic blood pressure. Hypertension was induced by DOCA-salt. Anti-inflammatory activity was carried out by carrageenan induced rat-paw oedema method. Test compounds 6b, 6c, 6e, 6f, 6j, 6h, 6k, 6l, 6m, 6n and 6o exerted comparative antihypertensive activity at 10 mg/kg dose level compared to nifedipine. Compounds 6j, 6m and 6o showed excellent results on evaluation by direct method. Test compounds 6a-6h, 6l, 6m, 6n and 6o exerted moderate to comparative anti-inflammatory activity at the 100 mg/kg dose level compared to indomethacin. Their further investigation for analgesic activity and acute ulcerogenesis was carried out, compounds 6m, 6f, 6k, 6o showed excellent to good analgesic activity and low ulcerogenic activity.

Quadriceps tendon ruptures in uremia.

Chronic renal failure and its sequelae, particularly secondary hyperparathyroidism, may be associated with spontaneous quadriceps tendon ruptures. This is a report of two cases of bilateral spontaneous simultaneous quadriceps tendon ruptures in uremia and a review of the literature. The level at which the tendon ruptures is inconstant. Light microscopy reveals nonspecific changes of degeneration and calcification. Under electron microscopy, the structure and maturity of collagen fibers are normal. The ruptures occur in patients younger than 40 years of age who reject medical treatment (i.e. oral phosphate binder) and have long-standing renal disease (mean = 12.3 years). The predisposing causes of rupture are unknown. An abnormality of collagen metabolism, ischemia, direct effects of parathormone, and dystrophic calcification are some of the possible contributory factors.

Bilateral simultaneous spontaneous rupture of quadriceps tendons in a diabetic patient.

We have described a case of bilateral simultaneous spontaneous quadriceps tendon rupture. The diagnosis is established by clinical examination. Definitive treatment consists of surgical repair followed by cylinder cast application for six to eight weeks.

Two-level thoracic disc herniation.

Herniation of thoracic discs at T6-7 and T7-8 occurred in a 41-year-old man. Thoracic disc disease is rare and the present case could be the first two-level herniation reported in the literature. The diagnosis was established by a myelogram (metrizamide) and computed tomographic (CT) scanning. The herniated discs were excised through a posterolateral approach. The preferred exposure is either translateral or transthoracic. Laminectomy is contraindicated, as it fails to correct spinal cord hemodynamics or relieve axial tension in the presence of an anterior epidural obstruction.