Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(4), P. 1131 - 1131

Published: April 15, 2020

An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed more than 211 countries or areas. This constant transmission a coronavirus and its ability to spread from human have prompted scientists develop new approaches for treatment COVID-19. A recent study shown remdesivir chloroquine effectively inhibit the replication infection severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) vitro. In United States, one case COVID-19 successfully treated compassionate use January 2020. addition, clinically proven protease inhibitor, camostat mesylate, been demonstrated Calu-3 SARS-CoV-2 prevent SARS-2-spike protein (S protein)-mediated entry into primary lung cells. Here, we systemically discuss pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase S infection. review should shed light on fundamental rationale behind inhibition enzymes RdRp as therapeutic management patients will viability challenges proteinase, application natural product quinoline analog Finally, determining structural-functional relationships provide insights interactions between angiotensin-converting enzyme 2 (ACE2) enable us SARS-CoV-2.

Language: Английский

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Review of the current state of protein aggregation inhibition from a materials chemistry perspective: special focus on polymeric materials

Materials Advances, Journal Year: 2021, Volume and Issue: 2(4), P. 1139 - 1176

Published: Jan. 1, 2021

This review discusses various aspects of protein aggregation and inhibition strategies, emphasizing the use polymers, which is one most promising approaches to combat aggregation-induced complications in neurodegenerative diseases therapeutics.

Language: Английский

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Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein

Life, Journal Year: 2022, Volume and Issue: 12(6), P. 897 - 897

Published: June 15, 2022

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype cancer cells. P-gp protein that regulates ATP-dependent efflux of wide range anticancer medicines and confers resistance. Due to its specificity, several attempts have been made block action restore efficacy drugs. The goal has create molecules either compete with for transport or function as direct inhibitor. Despite significant vitro success, there are presently no drugs available clinic can "block" P-gp-mediated Toxicity, unfavourable pharmacological interactions, variety pharmacokinetic difficulties might all be reason failure. On other hand, effect body. It protects vital organs from entry foreign bodies toxic chemicals. Hence, inhibitors should not hinder normal To develop an effective inhibitor P-gp, thorough background knowledge needed this field. main aim review article was set forth merits demerits on cells well influence drug delivery contribution activating were also mentioned.

Language: Английский

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Mesenchymal stromal cells (MSCs) for neurodegenerative disease: A promising frontier

European Journal of Cell Biology, Journal Year: 2020, Volume and Issue: 99(6), P. 151097 - 151097

Published: June 26, 2020

Language: Английский

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Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 25, 2020

Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane (EMC), comprising eight conserved subunits, has emerged as a central player this process. Yet, we have limited understanding of how EMC enables insertion integrity diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast human cryo-EM structures reveal intricate assemblies human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable activities, an insertase regulating levels broader role biogenesis. These depend on mechanistically coupled yet spatially distinct regions including lipid-accessible cavities which confer client-specific regulation, non-insertase function mediated by lumenal domain. Our illuminate structural mechanistic basis EMC's multifunctionality point its differentially client classes.

Language: Английский

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Aggregation of biologically important peptides and proteins: inhibition or acceleration depending on protein and metal ion concentrations

RSC Advances, Journal Year: 2019, Volume and Issue: 10(1), P. 215 - 227

Published: Dec. 24, 2019

The process of aggregation proteins and peptides is dependent on the concentration proteins, rate can be altered by presence metal ions, but this dependence not always a straightforward relationship. In general, does occur under normal physiological conditions, yet it induced in certain ions. However, extent influence ion interactions protein has been fully comprehended. A consensus thus difficult to reach because acceleration/inhibition ions depends several factors such as pH aggregated involved well level Metal like Cu2+, Zn2+, Pb2+ etc. may either accelerate or inhibit simply experimental conditions affect behavior biomolecules. It clear that understanding relationship between will prove useful for future scientific applications. This review focuses selected important biomolecules (peptides proteins) concentrations. We are prone aggregation, result which cause serious neurodegenerative disorders. Furthering our applications, finding therapies diseases.

Language: Английский

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Directed evolution in mammalian cells

Nature Methods, Journal Year: 2021, Volume and Issue: 18(4), P. 346 - 357

Published: April 1, 2021

Language: Английский

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Lipid Membrane Mimetics in Functional and Structural Studies of Integral Membrane Proteins

Membranes, Journal Year: 2021, Volume and Issue: 11(9), P. 685 - 685

Published: Sept. 3, 2021

Integral membrane proteins (IMPs) fulfill important physiological functions by providing cell-environment, cell-cell and virus-host communication; nutrients intake; export of toxic compounds out cells; more. However, some IMPs have obliterated due to polypeptide mutations, modifications in properties and/or other environmental factors-resulting damaged binding ligands the adoption non-physiological conformations that prevent protein from returning its state. Thus, elucidating IMPs' mechanisms function malfunction at molecular level is for enhancing our understanding cell organism physiology. This also helps pharmaceutical developments restoring or inhibiting activity. To this end, vitro studies provide invaluable information about structure relation between structural dynamics function. Typically, these are conducted on transferred native membranes membrane-mimicking nano-platforms (membrane mimetics) purified IMPs. Here, we review most widely used mimetics functional These detergents, liposomes, bicelles, nanodiscs/Lipodisqs, amphipols, lipidic cubic phases. We discuss protocols reconstitution as well applicability mimetic-IMP complexes via a variety biochemical, biophysical, biology techniques.

Language: Английский

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Targeting SLC transporters: small molecules as modulators and therapeutic opportunities

Trends in Biochemical Sciences, Journal Year: 2023, Volume and Issue: 48(9), P. 801 - 814

Published: June 22, 2023

Language: Английский

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The full spectrum of SLC22 OCT1 mutations illuminates the bridge between drug transporter biophysics and pharmacogenomics

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(10), P. 1932 - 1947.e10

Published: May 1, 2024

Language: Английский

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