scholarly journals Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1977
Author(s):  
Eleanor L. Atkinson ◽  
Jessica Iegre ◽  
Paul D. Brear ◽  
Elizabeth A. Zhabina ◽  
Marko Hyvönen ◽  
...  

Protein kinases are a large class of enzymes with numerous biological roles and many have been implicated in a vast array of diseases, including cancer and the novel coronavirus infection COVID-19. Thus, the development of chemical probes to selectively target each kinase is of great interest. Inhibition of protein kinases with ATP-competitive inhibitors has historically been the most widely used method. However, due to the highly conserved structures of ATP-sites, the identification of truly selective chemical probes is challenging. In this review, we use the Ser/Thr kinase CK2 as an example to highlight the historical challenges in effective and selective chemical probe development, alongside recent advances in the field and alternative strategies aiming to overcome these problems. The methods utilised for CK2 can be applied to an array of protein kinases to aid in the discovery of chemical probes to further understand each kinase’s biology, with wide-reaching implications for drug development.

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1198-1201
Author(s):  
Syed Yasir Afaque

In December 2019, a unique coronavirus infection, SARS-CoV-2, was first identified in the province of Wuhan in China. Since then, it spread rapidly all over the world and has been responsible for a large number of morbidity and mortality among humans. According to a latest study, Diabetes mellitus, heart diseases, Hypertension etc. are being considered important risk factors for the development of this infection and is also associated with unfavorable outcomes in these patients. There is little evidence concerning the trail back of these patients possibly because of a small number of participants and people who experienced primary composite outcomes (such as admission in the ICU, usage of machine-driven ventilation or even fatality of these patients). Until now, there are no academic findings that have proven independent prognostic value of diabetes on death in the novel Coronavirus patients. However, there are several conjectures linking Diabetes with the impact as well as progression of COVID-19 in these patients. The aim of this review is to acknowledge about the association amongst Diabetes and the novel Coronavirus and the result of the infection in such patients.


2020 ◽  
Vol 35 (9) ◽  
pp. 2675-2679 ◽  
Author(s):  
Katharine Lawrence ◽  
Kathleen Hanley ◽  
Jennifer Adams ◽  
Daniel J Sartori ◽  
Richard Greene ◽  
...  

Author(s):  
Maksim Leonidovich Maksimov ◽  
Albina Ayratovna Zvegintseva ◽  
Lyudmila Yurievna Kulagina ◽  
Albina Zainutdinovna Nigmedzyanova ◽  
Elvina Ramisovna Kadyseva

A review article is based on current foreign sources. The level of cytokines in the peripheral blood can be increased in many diseases, but in some cases there may be an excess of their normal concentration in tens, hundreds or more times with the development of a peculiar clinical picture, which is based on a systemic inflammatory reaction. In the literature this condition has received the figurative name «cytokine storm», which highlights an extremely violent reaction of the immune system with an unknown (often unfavorable) outcome. Close attention of the scientific world and the public to the problem of extremely high levels of cytokines in the peripheral blood (hypercytokinemia) was drawn due to the high frequency of the cytokine storm in the novel coronavirus infection.


2021 ◽  
Vol 100 (4) ◽  
pp. 74-79
Author(s):  
I.M. Kagantsov ◽  
◽  
V.V. Sizonov ◽  
V.G. Svarich ◽  
K.P. Piskunov ◽  
...  

The novel coronavirus infection (SARS-CoV-2), which first appeared in Wuhan, China in December 2019, has been declared a global pandemic by WHO. COVID-19 affects people of all age groups. The disease in children is usually asymptomatic or mild compared to adults, and with a significantly lower death rates. Data on kidney damage in children with COVID-19, as well as the effect of coronavirus infection on the course of diseases of the genitourinary system, are limited, the risks of contracting a new coronavirus infection in children with significant health problems, including those with chronic kidney disease, remain uncertain. The pandemic has affected the activities of surgeons treating diseases of the urinary system in children. Since the prospects for the end of the pandemic are vague, it is necessary to formulate criteria for selecting patients who can and should be provided with routine care in the pandemic. The purpose of this review is to highlight the features of the clinical manifestations and treatment of children with COVID-19, occurring against the background of previous renal pathology or complicating its course.


2021 ◽  
Vol 9_2021 ◽  
pp. 232-236
Author(s):  
Shklyaev A.E. Shklyaev A ◽  
Bessonov A.G. Bessonov A ◽  
Chushyalova D.A. Chushyalova D ◽  
Mikhailova M.D. Mikhailova M ◽  
Meleshkina M.V. Meleshkina M ◽  
...  

2021 ◽  
Vol 25 (1) ◽  
pp. 16-24
Author(s):  
O. B. Tamrazova ◽  
A. S. Stadnikova ◽  
E. V. Rudikova

In late 2019, a new viral infection appeared in China, which spread around the world, causing a pandemic. The causative agent of the new coronavirus infection COVID-19 is the SARS-CoV-2 coronavirus. The review presents modern data on the epidemiology, pathogenesis and course of the novel coronavirus infection COVID-19 in children. Chinese, American and European scientists have described a variety of cutaneous manifestations in children with COVID-19. The article provides a literature review of the cutaneous manifestations of COVID-19 coronavirus infection in children. During our own observation of 301 patients with coronavirus infection COVID-19 caused by SARS-CoV-2 at the Bashlyaevs Children Hospital in Moscow from May 17 to November 16, 2020, it was revealed that 39 (13 %) patients had skin manifestations. The article presents a classification of skin manifestations characteristic of COVID-19. A brief description of each group is given.


Author(s):  
И.Б. Симарова ◽  
С.Н. Переходов ◽  
А.Ю. Буланов

Гиперкоагуляционный характер коагулопатии, ассоциированной с новой коронавирусной инфекцией COVID-19, и высокий риск связанных с этим тромботических осложнений — хорошо известный факт на сегодняшний день. Тем не менее в литературе имеются описания и геморрагических событий у больных COVID. В обзоре приведен анализ публикаций, описывающих кровотечения при коронавирусной инфекции; общая частота их в среднем составляет 4–8%. Превалируют желудочно-кишечные кровотечения, существенную часть составляют межмышечные гематомы и кровоизлияния в кожу и слизистые. Показана предиктивная роль применения антикоагулянтов в терапевтических дозах и гипофибриногенемии. Отмечено отсутствие четкого понимания патофизиологических механизмов. Hypercoagulable character of coagulopathy associated with the novel coronavirus infection COVID-19, and the high risk of associated thrombotic complications is a well-known fact. However, there are also case reports of hemorrhagic events in COVID patients in the literature. The review summarizes the publications describing bleedings in coronavirus infection; their overall frequency is on average 4–8%. Gastrointestinal bleeding are prevalent, intermuscular hematomas and hemorrhages in the skin and mucous membranes are frequent. The predictive role of anticoagulants use in therapeutic doses and hypofibrinogenemia is shown. The absence of clear understanding of the pathophysiological mechanisms is noted.


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