Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against α-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies.

The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing.

Inhibition of amyloid formation along with modulation of toxicity employing small molecules is emerging as a potential therapeutic approach for protein misfolding disorders which includes Parkinson's disease, Alzheimer's disease and Multiple System Atrophy etc. Countless current interventional strategies for treating α-synucleinopathies consider using peptidic and non-peptidic inhibitors for arresting fibrillisation, disrupting existing fibrils and reducing associated toxicity. One group of molecules less exploited in this regard are triphenylmethane dyes. Herein we tested the inhibitory effect of two routinely used protein staining dyes viz Coomassie Brilliant blue G (CBBG) and Coomassie Brilliant blue R (CBBR) employing several biophysical and cell based methods. Our results showed that both the dyes not only efficiently inhibit fibrillisation but also disrupt existing fibrils. Nonetheless, only CBBR prevented the appearance of A11 epitopes which are marker of toxicity. Moreover, CBBR was also able to stall fibrillisation of A53T mutant α-synuclein and reduce associated neurotoxicity. This study thus reports the potential of CBBR as a therapeutic molecule.

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Sudden viral outbreaks have increased in the early part of the 21st century, such as those of severe acute respiratory syndrome coronavirus (SarS-coV), Middle east respiratory syndrome corona virus, and SarS-coV-2, owing to increased human access to wildlife habitats. Therefore, the likelihood of zoonotic transmission of human-associated viruses has increased. The emergence of severe acute respiratory syndrome coronavirus 2 in china and its spread worldwide within months have highlighted the need to be ready with advanced diagnostic and antiviral approaches to treat newly emerging diseases with minimal harm to human health. The gold-standard molecular diagnostic approaches currently used are time-consuming, require trained personnel and sophisticated equipment, and therefore cannot be used as point-of-care devices for widespread monitoring and surveillance. clustered regularly interspaced short palindromic repeats (criSPr)-associated (cas) systems are widespread and have been reported in bacteria, archaea and bacteriophages. criSPr-cas systems are organized into criSPr arrays and adjacent cas proteins. The detection and in-depth biochemical characterization of class 2 type V and Vi criSPr-cas systems and orthologous proteins such as cas12 and cas13 have led to the development of criSPr-based diagnostic approaches, which have been used to detect viral diseases and distinguish between serotypes and subtypes. criSPr-based diagnostic approaches detect human single nucleotide polymorphisms in samples from patients with cancer and are used as antiviral agents to detect and destroy viruses that contain rna as a genome. criSPr-based diagnostic approaches are likely to improve disease detection methods in the 21st century owing to their ease of development, low cost, reduced turnaround time, multiplexing and ease of deployment. The present review discusses the biochemical properties of cas12 and cas13 orthologs in viral disease detection and other applications. The present review expands the scope of criSPr-based diagnostic approaches to detect diseases and fight viruses as antivirals. Contents1. introduction 2. criSPr-cas systems provide tools for modern diagnostics 3. cas proteins recognize target double-stranded dna (dsdna) and rna mediated by single-stranded rna (ssrna)