Glutathione (GSH) is the most abundant cellular tripeptide (L-γglutamate-L-cysteinyl-glycine) which is as critical as oxygen and water. This low molecular mass antioxidant has a very high intracellular concentration that ranges from 1-10 mM and reaches extreme concentration points in malignant cell types. This defender of the cell is compartmentalized in mitochondria, nucleus, peroxisomes, endoplasmic reticulum (ER), and cytosol where it is synthesized. The enzymes involved in GSH redox cycling are important for both cellular free radical and nonradical detoxification. The present review article is covering the crucial roles of GSH to combat oxidative/nitrosative stress related to different diseases/disorders and possible drug designing for new therapies.

S-nitrosylation of proteins occurs as a consequence of the derivatization of cysteine thiols with nitric oxide (NO) and is often associated with diseases and protein malfunction. Aberrant S-nitrosylation, in addition to other genetic and epigenetic factors, has gained rapid importance as a prime cause of various metabolic, respiratory, and cardiac disorders, with a major emphasis on cancer and neurodegeneration. The S-nitrosoproteome, a term used to collectively refer to the diverse and dynamic repertoire of S-nitrosylated proteins, is relatively less explored in the field of redox biochemistry, in contrast to other covalently modified versions of the same set of proteins. Advancing research is gradually unveiling the enormous clinical importance of S-nitrosylation in the etiology of diseases and is opening up new avenues of prompt diagnosis that harness this phenomenon. Ever since the discovery of the two robust and highly conserved S-nitrosoglutathione reductase and thioredoxin systems as candidate denitrosylases, years of rampant speculation centered around the identification of specific substrates and other candidate denitrosylases, subcellular localization of both substrates and denitrosylases, the position of susceptible thiols, mechanisms of S-denitrosylation under basal and stimulus-dependent conditions, impact on protein conformation and function, and extrapolating these findings towards the understanding of diseases, aging and the development of novel therapeutic strategies. However, newer insights in the ever-expanding field of redox biology reveal distinct gaps in exploring the crucial crosstalk between the redoxins/major denitrosylase systems. Clarifying the importance of the functional overlap of the glutaredoxin, glutathione, and thioredoxin systems and examining their complementary functions as denitrosylases and antioxidant enzymatic defense systems are essential prerequisites for devising a rationale that could aid in predicting the extent of cell survival under high oxidative/nitrosative stress while taking into account the existence of the alternative and compensatory regulatory mechanisms. This review thus attempts to highlight major gaps in our understanding of the robust cellular redox regulation system, which is upheld by the concerted efforts of various denitrosylases and antioxidants.

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COVID-19 disease extended to different parts of the globe developing variations in the SARS-CoV-2 viral sequence since its emergence. Some of those variations had functional implications with major concerns, which the WHO termed as ‘Variant of Concern’ during the second wave of infection. The signatures of VOCs are specific to countries where they are observed and are popularly recognized with the country names. It is noteworthy to mention that some new mutations are always evolving and it is expected that some of these new mutations could play a havoc role in hitting the upcoming wave of the pandemic. This work aimed to list all the mutations of the Spike protein that evolved with time and how they have increased their presence in a given course of time (three-time point analysis) and stabilized in the SARS-COV-2 infected population. The mutations that will play predominant role in the upcoming pandemic wave are mentioned here:T19I, V213G, D405N, R408S,G142D, G339D, K417N, N440K, D614G, Q954H, N969K mutations in India; G142D, G339D, S373P, S375F, K417N, N440K, S477N, T478K, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K in South Africa; T95I, G339D, S373P, S375F, N501Y, D614G, H655Y in Brazil; G339D, S373P, S375F, K417N, N440K, N501Y, D614G, P681H in the UK.

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