Exploring Niclosamide as a Multi-target Drug Against SARS-CoV-2: Molecular Dynamics Simulation Studies on Host and Viral Proteins.

Niclosamide has emerged as a promising repurposed drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In vitro studies suggested that niclosamide inhibits the host transmembrane protein 16F (hTMEM16F), crucial for lipid scramblase activity, which consequently reduces syncytia formation that aids viral spread. Based on other in vitro reports, niclosamide may also target viral proteases such as papain-like protease (PLpro) and main protease (Mpro), essential for viral replication and maturation.

Evolution of drug resistance against antiviral agents that target cellular factors.

Antiviral drugs have classically been developed by directly disrupting the functions of viral proteins. However, this strategy has been largely unsuccessful due to the rapid generation of viral escape mutants. It has been well established that as compared to the virus-centric approach, the strategy of developing antiviral drugs by targeting host-dependency factors (HDFs) minimizes drug resistance.

A Rare Case of Endolymphatic Sac Tumour: Clinical, Radiological, Pathological and Immunohistochemical Findings with Review of Literature.

Endolymphatic sac tumour (ELST) is a rare low grade malignant epithelial tumour of the petrous temporal bone, thought to arise from papillary epithelium of the endolymphatic sac. They may occur sporadically or in association with Von-Hippel Lindau disease. ELST is extremely rare neoplasm with benign histopathological appearance and clinically destructive behaviour.

Toxic Leukoencephalopathy: An unusual Presentation by 5-Fluorouracil Infusion.

Background: Toxic leukoencephalopathy predominantly affect white matter of the brain parenchyma. Patient presents either in acute, subacute or chronic phase. The clinical presentation may vary, ranging from mild cognitive impairment to severe neurological dysfunction.

Clinico-radiological-pathological correlation in eumycetoma spectrum: Case series.

Maduramycosis or mycetoma is one of the chronic granulomatous diseases commonly seen in tropical regions. Microbiological cultures and biopsy are carried out for the definitive diagnosis of the disease, but they are time-consuming methods. The present study aims to correlate clinical, radiological and pathological features in eumycetoma cases to emphasize the role of "dot in circle" sign leading to early imaging-based diagnosis.

Potent Acetylcholinesterase Selective and Reversible Homodimeric Agent Based on Tacrine for Theranostics.

Acetylcholinesterase (AChE) has been an important biomarker for diagnosing Alzheimer's disease (AD), due to reduction in AChE activity in post-mortem brains of AD patients. A potent, selective, and reversible homodimeric inhibitor of AChE, 5-amino- N, N-bis(2-(1,2,3,4-tetrahydroacridin-9-ylamino)ethyl)isophthalamide (compound 4), was synthesized by using 9-alkyl(1,2,3,4-tetrahydroacridine) pharmacophore with appended functionality. In the present work, we report the synthesis of this bivalent inhibitor of AChE.

Acute Encephalitis with Atypical Presentation of Rubella in Family Cluster, India.

We report 3 atypical rubella cases in a family cluster in India. The index case-patient showed only mild febrile illness, whereas the other 2 patients showed acute encephalitis and died of the disease. We confirmed rubella in the index and third cases using next-generation sequencing and IgM.

Radiolabeling and Preclinical Evaluation of a New S-Alkylated Cysteine Derivative Conjugated to C-Substituted Macrocycle for Positron Emission Tomography.

A new S-alkylated cysteine-derivatized tumor targeting agent, 2,2'-(12-(2-((2-acetamido-2-carboxyethyl)thio)acetamido)-11,13-dioxo-1,4,7,10-tetraazacyclotridecane-4,7-diyl)diacetic acid was developed for positron emission tomography (PET) imaging. -Acetyl cysteine (NAC) was conjugated to ATRIDAT as a specific targeting agent toward L-type and ASC amino acid transporter systems in the oncogenic cells. NAC was attached via S-alkylation to prevent its incorporation at undesired recognition sites affecting the signal-to-noise ratio.

Rose Bengal attached and dextran coated gadolinium oxide nanoparticles for potential diagnostic imaging applications.

We report here, reverse micelle mediated synthesis of multifunctional dextran (dex) coated GdO nanoparticles (NPs) carrying rose bengal (RB) dye for magnetic resonance and optical imaging. The diameter of these RB attached dex coated GdO NPs (Gd-dex-RB NPs) was found to be ~17 nm as measured by TEM. NMR line broadening effect on the surrounding water protons affirmed the paramagnetic nature of these NPs.

[Ga]/[Re] Complexed [CDTMP] Trans-1,2-Cyclohexyldinitrilotetraphosphonic Acid As a Theranostic Agent for Skeletal Metastases.

Objective: Metastasis of the osseous tissue is one of the frequent and severe aggravations as a result of several neoplastic conditions, such as metabolic disorders, infections, and cancer. The objective of this study was to evaluate the pertinence of [Ga]-trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid (CDTMP) as a potential bone imaging agent for positron emission tomography (PET) applications as well as to assess [Re]-CDTMP for bone pain palliation in metastatic skeletal disorders.

Methods: Ga complex of CDTMP was prepared at 80°C at pH 3.

PEG coated and doxorubicin loaded multimodal Gadolinium oxide nanoparticles for simultaneous drug delivery and imaging applications.

We report water-in-oil microemulsion mediated synthesis of PEG coated GdO NPs loaded with fluorescent anti-cancer drug dox for synchronous drug delivery, optical and MR imaging applications. These PEG covered GdO NPs loaded with dox (Gd-PEG-dox NPs) were found to possess spherical morphology with 13nm size as measured from TEM and the hydrodynamic diameter comes out to be 37nm as determined from DLS. Fluorescence spectra and fluorescence microscopy images confirmed optical activity of the NPs.

Biotinidase Resistant Gallium-Radioligand Based on Biotin/Avidin Interaction for Pretargeting: Synthesis and Preclinical Evaluation.

A new macrocyclic system 2,2'-(12-amino-11,13-dioxo-1,4,7,10-tetraazacyclotridecane-4,7-diyl)diacetic acid (ATRIDAT) was designed for coordinating metals in +2 and +3 oxidation states particularly Ga(III), for PET imaging. ATRIDAT was conjugated to d-biotin for pretargeting via biotin-avidin interaction. This model provides high tumor targeting efficiency and stability to biotinidase activity leading to modest signal amplification at the tumor site.

FITC-Dextran entrapped and silica coated gadolinium oxide nanoparticles for synchronous optical and magnetic resonance imaging applications.

We report, microemulsion mediated synthesis of FITC-dextran dye entrapped and silica coated Gd2O3 nanoparticles (NPs) for dual purpose of optical and magnetic resonance imaging, in the present study. TEM image revealed that the average size of the NPs is 18nm and hydrodynamic diameter of the particles as measured by DLS comes out to be about 16nm. Gd2O3 core show paramagnetism which is affirmed by the NMR line broadening effect on neighboring water proton spectrum and also by magnetization curve obtained in VSM analysis.

Preclinical Evaluation of a Potential GSH Ester Based PET/SPECT Imaging Probe DT(GSHMe)₂ to Detect Gamma Glutamyl Transferase Over Expressing Tumors.

Gamma Glutamyl Transferase (GGT) is an important biomarker in malignant cancers. The redox processes ensuing from GGT-mediated metabolism of extracellular GSH are implicated in critical aspects of tumor cell biology. Reportedly, Glutathione monoethyl ester (GSHMe) is a substrate of GGT, which has been used for its rapid transport over glutathione.

LAT1 targeted delivery of methionine based imaging probe derived from M(III) metal ions for early diagnosis of proliferating tumours using molecular imaging modalities.

We investigated the potential of DTPA-bis(Methionine), a target specific amino acid based probe for detection of L-type amino acid transporters (LAT1) known to over express in proliferating tumours using multimodality imaging. The ligand, DTPA-bis(Met) was readily converted to lanthanide complexes and was found capable of targeting cancer cells using multimodality imaging. DTPA-bis(Met) complexes were synthesized and characterized by mass spectroscopy.