Inherited/Genetically-Associated Pheochromocytoma/ Paraganglioma Syndromes and COVID-19

In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1α-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1α vis-à-vis COVID-19 could open ways of therapeutic interventions.

Genetic changes involving the coral gastrovascular system support the transition between colonies and bailed-out polyps: evidence from a Pocillopora acuta transcriptome

Background A coral colony is composed of physiologically integrated polyps. In stony corals, coloniality adopts a wide diversity of forms and involves complex ontogenetic dynamics. However, molecular mechanisms underlying coloniality have been little studied. To understand the genetic basis of coloniality and its contribution to coral ecology, we induced polyp bail-out in a colonial coral, Pocillopora acuta, and compared transcription profiles of bailed-out polyps and polyps in normal colonies, and their responses to heat shock and hyposalinity. Results Consistent with morphological formation of a gastrovascular system and its neural transmission and molecular transport functions, we found genetic activation of neurogenesis and development of tube-like structures in normal colonies that is absent in bailed-out polyps. Moreover, relative to bailed-out polyps, colonies showed significant overexpression of genes for angiotensin-converting enzymes and endothelin-converting enzymes. In response to hyperthermal and hyposaline treatments, a high proportion of genetic regulation proved specific to either bailed-out polyps or colonies. Elevated temperatures even activated NF-κB signaling in colonies. On the other hand, colonies showed no discernible advantage over bailed-out polyps in regard to hyposalinity. Conclusions The present study provides a first look at the genetic basis of coloniality and documents different responses to environmental stimuli in P. acuta colonies versus those in bailed-out polyps. Overexpression of angiotensin-converting enzymes and endothelin-converting enzymes in colonies suggests possible involvement of these genes in development of the gastrovascular system in P. acuta. Functional characterization of these coral genes and further investigation of other forms of the transition to coloniality in stony corals should be fruitful areas for future research.

Seaweed-Based Interventions for Diabetic Complications: An Analytical Discourse

Modern sedentary lifestyle has given rise to a number of health issues; diabetes mellitus is one of them, another worldwide emergency, which is usually attributed either by deficiency or by insensitivity of insulin hormone; the master-regulator of blood glucose level. Seaweeds are rich reservoirs of a plethora of bioactive compounds with a great assortment of therapeutic potential. The goal of this communication is to represent the state-of-the-art about what is known for the anti-hyperglycemic properties recognized in seaweeds, emphasizing about their assets of several bioactive principles, their modes of action over targets of pharmacological interest, in addition to their precise extraction procedures. Various bioactive molecules from seaweed origin, mainly polyphenols, can inhibit several drug targets like α-glucosidase, α-amylase, aldose reductase, protein tyrosine phosphatase 1B, angiotensin-converting enzymes and dipeptidyl peptidase-4 to achieve good glycemic control.

Angiotensin-(3-4) modulates the overweight- and undernutrition-induced ACE2 downregulation in renal proximal tubule cells: implications for COVID-19?

Aim: The renal lesions–including severe acute kidney injury–are severe outcomes in severe acute respiratory syndrome coronavirus 2 infections. There are no reports regarding the influence of the nutritional status on the severity and progress of these lesions. Ageing is also an important risk factor. Methods: In the present study we compared the influence of overweight and undernutrition on the levels of renal angiotensin converting enzymes 1 and 2 (ACE and ACE2), which were evaluated by Western blotting. Since the renin-angiotensin-aldosterone system (RAAS) has been implicated in the progress of kidney failure during coronavirus disease 2019, the influence of Angiotensin-(3-4) [Ang-(3-4)] was investigated. Ang-(3-4) is the shortest angiotensin-derived peptide, which is considered the physiological antagonist of several Ang II effects. Results: Both overweight and undernutrition downregulate the levels of ACE2 without influence on the levels of ACE in proximal tubules from kidney rats. Administration of Ang-(3-4) upregulates ACE2 to levels above the control in overweight but not in undernourished rats. Conclusions: Chronic undernourishment and overnourishment conditions play a central role in the renal ACE/ACE2 balance, and that the role of RAAS is also different in overweight and undernutrition.

AIDrugApp: Artificial Intelligence-based Web-App for Virtual Screening of Inhibitors against SARS-COV-2

<p>Currently, there is no effective cure for SARS-COVID-19 diseases. The identification of novel therapeutic targets and drug-like compounds is required for the development of anti-COVID-19 drugs. Virtual screening is currently the most significant component for identifying drug-like molecules from large datasets for drug design and development. But there are no effective easily available and user-friendly applications for virtual screening of drug leads against SARS-COV-2. Therefore, we have developed a user-friendly web-app named “AIDrugApp” for the virtual screening of inhibitor molecules against SARS-CoV-2. AIDrugApp is a novel open-access, deep learning AI-based inhibitory activity prediction and data statistics visualization platform. Users can predict the inhibitory activities (Active/ Inactive) and pIC-50 values of new compounds against SARS-CoV-2 replicase polyprotein, 3CLpro and human angiotensin-converting enzymes. It is also useful for virtual screening of chemical features of molecules towards SARS-COVID-19 clinical trial bioactivities. This paper presents the development and architecture of AIDrugApp. We also present two case studies where large sets of molecules were screened by our app. Screened molecules were analyzed further by molecular docking and ADME analysis to identify the potential drug candidates. </p> <p><b>Web-App URL:</b> <a href="https://sars-covid-app.herokuapp.com/">https://sars-covid-app.herokuapp.com/</a></p>

AIDrugApp: Artificial Intelligence-based Web-App for Virtual Screening of Inhibitors against SARS-COV-2

<p>Currently, there is no effective cure for SARS-COVID-19 diseases. The identification of novel therapeutic targets and drug-like compounds is required for the development of anti-COVID-19 drugs. Virtual screening is currently the most significant component for identifying drug-like molecules from large datasets for drug design and development. But there are no effective easily available and user-friendly applications for virtual screening of drug leads against SARS-COV-2. Therefore, we have developed a user-friendly web-app named “AIDrugApp” for the virtual screening of inhibitor molecules against SARS-CoV-2. AIDrugApp is a novel open-access, deep learning AI-based inhibitory activity prediction and data statistics visualization platform. Users can predict the inhibitory activities (Active/ Inactive) and pIC-50 values of new compounds against SARS-CoV-2 replicase polyprotein, 3CLpro and human angiotensin-converting enzymes. It is also useful for virtual screening of chemical features of molecules towards SARS-COVID-19 clinical trial bioactivities. This paper presents the development and architecture of AIDrugApp. We also present two case studies where large sets of molecules were screened by our app. Screened molecules were analyzed further by molecular docking and ADME analysis to identify the potential drug candidates. </p> <p><b>Web-App URL:</b> <a href="https://sars-covid-app.herokuapp.com/">https://sars-covid-app.herokuapp.com/</a></p>