COVID 19: AN OVERVIEW OF PATHOGENESIS, CYTOKINE STORM AND INTERFERONS AS A POTENTIAL DRUG THERAPY

Novel Coronavirus (SARS-CoV-2) causing Coronavirus disease (COVID-19) has become a pandemic and has not been previously identified in humans. Transmission among humans occurs through respiratory droplets of infected individual. Patients infected with SARS-CoV-2 undergo acute respiratory distress because of Cytokine storm which serve as the major cause of morbidity and mortality in affected individuals. Cytokines are defined as non-structural proteins which are small with low molecular weight and have a greater regulatory influence in inflammation and immunity. They are considered as the intercellular messenger in the immune system. Therefore, this article provides a glimpse of advancements made in the area of SARS-CoV-2 infection where Cytokines may be a useful biomarker for both diagnostic and prognostic purpose and also as a therapeutic agent in targeting certain cytokines responsible for Acute Respiratory Distress Syndrome (ARDS) in SARS-CoV-2 infected patients.

Independent origins of neurons and synapses: insights from ctenophores

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses suggest that both electrical and chemical synapses evolved more than once.

Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.

Modulation of swimming in the gastropod Melibe leonina by nitric oxide

SUMMARY Nitric oxide (NO) is a gaseous intercellular messenger produced by the enzyme nitric oxide synthase. It has been implicated as a neuromodulator in several groups of animals, including gastropods, crustaceans and mammals. In this study, we investigated the effects of NO on the swim motor program produced by isolated brains and by semi-intact preparations of the nudibranch Melibe leonina. The NO donors sodium nitroprusside (SNP, 1 mmol l–1) and S-nitroso-N-acetylpenicillamine (SNAP, 1 mmol l–1) both had a marked effect on the swim motor program expressed in isolated brains, causing an increase in the period of the swim cycle and a more erratic swim rhythm. In semi-intact preparations, the effect of NO donors was manifested as a significant decrease in the rate of actual swimming. An NO scavenger, reduced oxyhemoglobin, eliminated the effects of NO donors on isolated brains, supporting the assumption that the changes in swimming induced by donors were actually due to NO. The cGMP analogue 8-bromoguanosine 3′,5′-cyclic monophosphate (1 mmol l–1) produced effects that mimicked those of NO donors, suggesting that NO is working via a cGMP-dependent mechanism. These results, in combination with previous histological studies indicating the endogenous presence of nitric oxide synthase, suggest that NO is used in the central nervous system of Melibe leonina to modulate swimming.

Inducible NO synthase: role in cellular signalling

The discovery of endothelium-derived relaxing factor and its identification as nitric oxide (NO) was one of the most exciting discoveries of biomedical research in the 1980s. Besides its potent vasodilatory effects, NO was found under certain circumstances to be responsible for the killing of microorganisms and tumour cells by activated macrophages and to act as a novel, unconventional type of neurotransmitter. In 1992, Science picked NO as the ‘Molecule of the Year’, and over the past years NO has become established as a universal intercellular messenger that acutely affects important signalling pathways and, on a more long-term scale, modulates gene expression in target cells. These actions will form the focus of the present review.

Stimulation of soluble guanylate cyclase by superoxide dismutase is mediated by NO

Soluble guanylate cyclase (sGC), which is found in many cells and tissues, represents the receptor for the intra- and intercellular messenger molecule NO. Superoxide dismutase (SOD), an enzyme involved in the degradation of toxic superoxide radicals, has been proposed as a non-NO activator of sGC. Here we show that SOD stimulated sGC purified from bovine lung up to 10-fold. Activation by SOD was not influenced by the hydroxyl radical scavengers mannitol and DMSO. In contrast, the presence of the NO scavengers oxyhaemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, as well as the O2--generating system xanthine oxidase/hypoxanthine, led to inhibition of SOD-stimulated cGMP production. NO-insensitive sGC mutants were not influenced either by SOD or by xanthine oxidase. We have previously shown that sGC was stimulated by NO present in the normal atmosphere. Here we show that the SOD effect depended on the NO concentration from the atmosphere, as the stimulation of sGC by defined NO gases (0, 120, 330 and 1000 parts per billion NO) was potentiated by SOD. NO stimulation of sGC and its potentiation by SOD were inhibited by oxyhaemoglobin to identical levels. We conclude that the SOD-mediated stimulation of sGC is due to the elimination of superoxide, thereby preventing its reaction with NO to form peroxynitrite.