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1.
Int J Mol Sci ; 23(5)2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1736947

ABSTRACT

N-(4-((3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)selanyl)phenyl)acetamide (5), C19H15NO3Se, was prepared in two steps from 4,4'-diselanediyldianiline (3) via reduction and subsequent nucleophilic reaction with 2-methyl-3-bromo-1,4-naphthalenedione, followed by acetylation with acetic anhydride. The cytotoxicity was estimated against 158N and 158JP oligodendrocytes and the redox profile was also evaluated using different in vitro assays. The technique of single-crystal X-ray diffraction is used to confirm the structure of compound 5. The enantiopure 5 crystallizes in space group P21 with Flack parameter 0.017 (8), exhibiting a chiral layered absolute structure. Molecular structural studies showed that the crystal structure is foremost stabilized by N-H···O and relatively weak C-H···O contacts between molecules, and additionally stabilized by weak C-H···π and Se···N interactions. Hirshfeld surface analysis is used to quantitatively investigate the noncovalent interactions that stabilize crystal packing. Framework energy diagrams were used to graphically represent the stabilizing interaction energies for crystal packing. The analysis of the energy framework shows that the interactions energies of and C-H···π and C-O···π are primarily dispersive and are the crystal's main important forces. Density functional theory (DFT) calculations were used to determine the compound's stability, chemical reactivity, and other parameters by determining the HOMO-LUMO energy differences. The determination of its optimized surface of the molecular electrostatic potential (MEP) was also carried out. This study was conducted to demonstrate both the electron-rich and electron-poor sites.


Subject(s)
Halogens , Hydrogen , Acetamides , Crystallography, X-Ray , Density Functional Theory , Hydrogen Bonding
2.
Medicine (Baltimore) ; 101(9): e27759, 2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1730756

ABSTRACT

ABSTRACT: A global public health crisis caused by the 2019 novel coronavirus disease (COVID-19) leads to considerable morbidity and mortality, which bring great challenge to respiratory medicine. Hydrogen-oxygen therapy contributes to treat severe respiratory diseases and improve lung functions, yet there is no information to support the clinical use of this therapy in the COVID-19 pneumonia.A retrospective study of medical records was carried out in Shishou Hospital of Traditional Chinese Medicine in Hubei, China. COVID-19 patients (aged ≥ 30 years) admitted to the hospital from January 29 to March 20, 2020 were subjected to control group (n = 12) who received routine therapy and case group (n = 12) who received additional hydrogen-oxygen therapy. The clinical characteristics of COVID-19 patients were analyzed. The physiological and biochemical indexes, including immune inflammation indicators, electrolytes, myocardial enzyme profile, and functions of liver and kidney, were examined and investigated before and after hydrogen-oxygen therapy.The results showed significant decreases in the neutrophil percentage and the concentration and abnormal proportion of C-reactive protein in COVID-19 patients received additional hydrogen-oxygen therapy.This novel therapeutic may alleviate clinical symptoms of COVID-19 patients by suppressing inflammation responses.


Subject(s)
COVID-19/therapy , Hydrogen/therapeutic use , Oxygen/therapeutic use , Adult , China/epidemiology , Female , Humans , Inflammation , Male , Medical Records , Middle Aged , Oxygen Inhalation Therapy , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
3.
Mol Med ; 28(1): 27, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1724403

ABSTRACT

Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.


Subject(s)
Acute Lung Injury/drug therapy , COVID-19/drug therapy , Hydrogen/pharmacology , Protective Agents/pharmacology , Acute Lung Injury/physiopathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Humans , Sepsis/drug therapy , Sepsis/physiopathology
4.
J Zhejiang Univ Sci B ; 23(2): 102-122, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1706587

ABSTRACT

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Hydrogen/therapeutic use , Lung Diseases/therapy , Acute Lung Injury , Aging , Animals , Anti-Inflammatory Agents , Antioxidants/chemistry , Asthma/therapy , Autophagy , COVID-19/drug therapy , Humans , Hypertension, Pulmonary/therapy , Inflammation , Lung Neoplasms/therapy , Mice , Oxidative Stress , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Fibrosis/therapy , Pyroptosis , Reactive Oxygen Species
5.
Int J Environ Res Public Health ; 19(4)2022 02 10.
Article in English | MEDLINE | ID: covidwho-1690248

ABSTRACT

Molecular hydrogen (H2) is potentially a novel therapeutic gas for acute post-coronavirus disease 2019 (COVID-19) patients because it has antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties. The aim of this study was to determine the effect of 14 days of H2 inhalation on the respiratory and physical fitness status of acute post-COVID-19 patients. This randomized, single-blind, placebo-controlled study included 26 males (44 ± 17 years) and 24 females (38 ± 12 years), who performed a 6-min walking test (6 MWT) and pulmonary function test, specifically forced vital capacity (FVC) and expiratory volume in the first second (FEV1). Symptomatic participants were recruited between 21 and 33 days after a positive polymerase chain reaction test. The experiment consisted of H2/placebo inhalation, 2 × 60 min/day for 14 days. Results showed that H2 therapy, compared with placebo, significantly increased 6 MWT distance by 64 ± 39 m, FVC by 0.19 ± 0.24 L, and, in FEV1, by 0.11 ± 0.28 L (all p ≤ 0.025). In conclusion, H2 inhalation had beneficial health effects in terms of improved physical and respiratory function in acute post-COVID-19 patients. Therefore, H2 inhalation may represent a safe, effective approach for accelerating early function restoration in post-COVID-19 patients.


Subject(s)
COVID-19 , Female , Forced Expiratory Volume , Humans , Hydrogen/therapeutic use , Male , Respiratory Function Tests , SARS-CoV-2 , Single-Blind Method
6.
Oxid Med Cell Longev ; 2021: 5513868, 2021.
Article in English | MEDLINE | ID: covidwho-1467753

ABSTRACT

COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.


Subject(s)
COVID-19 , Hydrogen/therapeutic use , Oxidative Stress/drug effects , SARS-CoV-2/metabolism , Signal Transduction/drug effects , COVID-19/drug therapy , COVID-19/metabolism , Humans , Inflammation/drug therapy , Inflammation/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism
7.
Biomol NMR Assign ; 15(1): 219-227, 2021 04.
Article in English | MEDLINE | ID: covidwho-1384623

ABSTRACT

The nucleocapsid protein N from SARS-CoV-2 is one of the most highly expressed proteins by the virus and plays a number of important roles in the transcription and assembly of the virion within the infected host cell. It is expected to be characterized by a highly dynamic and heterogeneous structure as can be inferred by bioinformatics analyses as well as from the data available for the homologous protein from SARS-CoV. The two globular domains of the protein (NTD and CTD) have been investigated while no high-resolution information is available yet for the flexible regions of the protein. We focus here on the 1-248 construct which comprises two disordered fragments (IDR1 and IDR2) in addition to the N-terminal globular domain (NTD) and report the sequence-specific assignment of the two disordered regions, a step forward towards the complete characterization of the whole protein.


Subject(s)
Coronavirus Nucleocapsid Proteins/chemistry , Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Carbon Isotopes , Computational Biology , Hydrogen , Nitrogen Isotopes , Phosphoproteins/chemistry , Protein Binding , Protein Domains , Protein Structure, Secondary
8.
Biomol NMR Assign ; 15(1): 165-171, 2021 04.
Article in English | MEDLINE | ID: covidwho-1384622

ABSTRACT

SARS-CoV-2 RNA, nsP3c (non-structural Protein3c) spans the sequence of the so-called SARS Unique Domains (SUDs), first observed in SARS-CoV. Although the function of this viral protein is not fully elucidated, it is believed that it is crucial for the formation of the replication/transcription viral complex (RTC) and of the interaction of various viral "components" with the host cell; thus, it is essential for the entire viral life cycle. The first two SUDs, the so-called SUD-N (the N-terminal domain) and SUD-M (domain following SUD-N) domains, exhibit topological and conformational features that resemble the nsP3b macro (or "X") domain. Indeed, they are all folded in a three-layer α/ß/α sandwich structure, as revealed through crystallographic structural investigation of SARS-CoV SUDs, and they have been attributed to different substrate selectivity as they selectively bind to oligonucleotides. On the other hand, the C-terminal SUD (SUD-C) exhibit much lower sequence similarities compared to the SUD-N & SUD-M, as reported in previous crystallographic and NMR studies of SARS-CoV. In the absence of the 3D structures of SARS-CoV-2, we report herein the almost complete NMR backbone and side-chain resonance assignment (1H,13C,15N) of SARS-CoV-2 SUD-M and SUD-C proteins, and the NMR chemical shift-based prediction of their secondary structure elements. These NMR data will set the base for further understanding at the atomic-level conformational dynamics of these proteins and will allow the effective screening of a large number of small molecules as binders with potential biological impact on their function.


Subject(s)
Coronavirus Papain-Like Proteases/chemistry , Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Carbon Isotopes , Hydrogen , Nitrogen Isotopes , Protein Binding , Protein Domains , Protein Structure, Secondary
9.
Biomol NMR Assign ; 15(1): 85-89, 2021 04.
Article in English | MEDLINE | ID: covidwho-1384621

ABSTRACT

Among the proteins encoded by the SARS-CoV-2 RNA, nsP3 (non-structural Protein3) is the largest multi-domain protein. Its role is multifaceted and important for the viral life cycle. Nonetheless, regarding the specific role of each domain there are many aspects of their function that have to be investigated. SARS Unique Domains (SUDs), constitute the nsP3c region of the nsP3, and were observed for the first time in SARS-CoV. Two of them, namely SUD-N (the first SUD) and the SUD-M (sequential to SUD-N), exhibit structural homology with nsP3b ("X" or macro domain); indeed all of them are folded in a three-layer α/ß/α sandwich. On the contrary, they do not exhibit functional similarities, like ADP-ribose binding properties and ADP-ribose hydrolase activity. There are reports that suggest that these two SUDs may exhibit a binding selectivity towards G-oligonucleotides, a feature which may contribute to the characterization of their role in the formation of the replication/transcription viral complex (RTC) and of the interaction of various viral "components" with the host cell. While the structures of these domains of SARS-CoV-2 have not been determined yet, SUDs interaction with oligonucleotides and/or RNA molecules may provide a platform for drug discovery. Here, we report the almost complete NMR backbone and side-chain resonance assignment (1H,13C,15N) of SARS-CoV-2 SUD-N protein, and the NMR chemical shift-based prediction of the secondary structure elements. These data may be exploited for its 3D structure determination and the screening of chemical compounds libraries, which may alter SUD-N function.


Subject(s)
Coronavirus Papain-Like Proteases/chemistry , Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Carbon Isotopes , Drug Design , Hydrogen , Nitrogen Isotopes , Oligonucleotides/chemistry , Protein Domains , Protein Structure, Secondary , Virus Replication
10.
Curr Pharm Des ; 27(5): 667-678, 2021.
Article in English | MEDLINE | ID: covidwho-1369589

ABSTRACT

Sepsis is the main cause of death in critically ill patients with no effective treatment. Sepsis is lifethreatening organ dysfunction due to a dysregulated host response to infection. As a novel medical gas, molecular hydrogen (H2) has a therapeutic effect on many diseases, such as sepsis. H2 treatment exerts multiple biological effects, which can effectively improve multiple organ injuries caused by sepsis. However, the underlying molecular mechanisms of hydrogen involved in the treatment of sepsis remain elusive, which are likely related to anti-inflammation, anti-oxidation, anti-apoptosis, regulation of autophagy and multiple signaling pathways. This review can help better understand the progress of hydrogen in the treatment of sepsis, and provide a theoretical basis for the clinical application of hydrogen therapy in sepsis in the future.


Subject(s)
Sepsis , Anti-Inflammatory Agents/therapeutic use , Autophagy , Cell Death , Humans , Hydrogen/therapeutic use , Sepsis/drug therapy
11.
Biomol NMR Assign ; 15(1): 65-71, 2021 04.
Article in English | MEDLINE | ID: covidwho-1184741

ABSTRACT

The international Covid19-NMR consortium aims at the comprehensive spectroscopic characterization of SARS-CoV-2 RNA elements and proteins and will provide NMR chemical shift assignments of the molecular components of this virus. The SARS-CoV-2 genome encodes approximately 30 different proteins. Four of these proteins are involved in forming the viral envelope or in the packaging of the RNA genome and are therefore called structural proteins. The other proteins fulfill a variety of functions during the viral life cycle and comprise the so-called non-structural proteins (nsps). Here, we report the near-complete NMR resonance assignment for the backbone chemical shifts of the non-structural protein 10 (nsp10). Nsp10 is part of the viral replication-transcription complex (RTC). It aids in synthesizing and modifying the genomic and subgenomic RNAs. Via its interaction with nsp14, it ensures transcriptional fidelity of the RNA-dependent RNA polymerase, and through its stimulation of the methyltransferase activity of nsp16, it aids in synthesizing the RNA cap structures which protect the viral RNAs from being recognized by the innate immune system. Both of these functions can be potentially targeted by drugs. Our data will aid in performing additional NMR-based characterizations, and provide a basis for the identification of possible small molecule ligands interfering with nsp10 exerting its essential role in viral replication.


Subject(s)
Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Viral Regulatory and Accessory Proteins/chemistry , Amino Acid Motifs , Carbon Isotopes , Exoribonucleases/chemistry , Hydrogen , Hydrogen Bonding , Ligands , Methyltransferases , Nitrogen Isotopes , Protein Structure, Secondary , RNA, Viral , Viral Envelope , Viral Nonstructural Proteins/chemistry , Virus Replication , Zinc Fingers
12.
Arch Pharm (Weinheim) ; 354(4): e2000378, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1162498

ABSTRACT

Many diseases as well as acute conditions can lead to fatigue, which can be either temporary or chronic in nature. Acute fatigue develops frequently after physical exercise or after alcohol hangover, whereas microbial infections such as influenza or COVID-19 and chronic diseases like Parkinson's disease or multiple sclerosis are often associated with chronic fatigue. Oxidative stress and a resulting disturbance of mitochondrial function are likely to be common denominators for many forms of fatigue, and antioxidant treatments have been shown to be effective in alleviating the symptoms of fatigue. In this study, we review the role of reactive oxygen and nitrogen species in fatigue and the antioxidant effects of the intake of molecular hydrogen. We propose that molecular hydrogen is well suited for the treatment of temporary and chronic forms of oxidative stress-associated fatigue.


Subject(s)
COVID-19 , Fatigue , Hydrogen , Oxidative Stress , Antioxidants/metabolism , Antioxidants/pharmacology , COVID-19/metabolism , COVID-19/physiopathology , Fatigue/etiology , Fatigue/metabolism , Fatigue/therapy , Humans , Hydrogen/metabolism , Hydrogen/pharmacology , Nitrogen , Oxidative Stress/drug effects , Oxidative Stress/physiology , Quantitative Structure-Activity Relationship , Reactive Oxygen Species , SARS-CoV-2
13.
Biomol NMR Assign ; 15(1): 153-157, 2021 04.
Article in English | MEDLINE | ID: covidwho-1141506

ABSTRACT

Coronaviruses have become of great medical and scientific interest because of the Covid-19 pandemic. The hCoV-HKU1 is an endemic betacoronavirus that causes mild respiratory symptoms, although the infection can progress to severe lung disease and death. During viral replication, a discontinuous transcription of the genome takes place, producing the subgenomic messenger RNAs. The nucleocapsid protein (N) plays a pivotal role in the regulation of this process, acting as an RNA chaperone and participating in the nucleocapsid assembly. The isolated N-terminal domain of protein N (N-NTD) specifically binds to the transcriptional regulatory sequences and control the melting of the double-stranded RNA. Here, we report the resonance assignments of the N-NTD of HKU1-CoV.


Subject(s)
Betacoronavirus/chemistry , Coronavirus Nucleocapsid Proteins/chemistry , Magnetic Resonance Spectroscopy , Carbon Isotopes , Escherichia coli/metabolism , Hydrogen , Nitrogen Isotopes , Protein Binding , Protein Domains , Protein Structure, Secondary , Software
14.
Biomol NMR Assign ; 15(1): 129-135, 2021 04.
Article in English | MEDLINE | ID: covidwho-1141504

ABSTRACT

The current outbreak of the highly infectious COVID-19 respiratory disease is caused by the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). To fight the pandemic, the search for promising viral drug targets has become a cross-border common goal of the international biomedical research community. Within the international Covid19-NMR consortium, scientists support drug development against SARS-CoV-2 by providing publicly available NMR data on viral proteins and RNAs. The coronavirus nucleocapsid protein (N protein) is an RNA-binding protein involved in viral transcription and replication. Its primary function is the packaging of the viral RNA genome. The highly conserved architecture of the coronavirus N protein consists of an N-terminal RNA-binding domain (NTD), followed by an intrinsically disordered Serine/Arginine (SR)-rich linker and a C-terminal dimerization domain (CTD). Besides its involvement in oligomerization, the CTD of the N protein (N-CTD) is also able to bind to nucleic acids by itself, independent of the NTD. Here, we report the near-complete NMR backbone chemical shift assignments of the SARS-CoV-2 N-CTD to provide the basis for downstream applications, in particular site-resolved drug binding studies.


Subject(s)
Coronavirus Nucleocapsid Proteins/chemistry , Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Carbon Isotopes , Crystallography, X-Ray , Dimerization , Drug Design , Hydrogen , Hydrogen-Ion Concentration , Nitrogen Isotopes , Phosphoproteins/chemistry , Protein Binding , Protein Domains , Protein Interaction Mapping , Protein Structure, Secondary
15.
Biomol NMR Assign ; 15(1): 73-77, 2021 04.
Article in English | MEDLINE | ID: covidwho-1141500

ABSTRACT

The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project covid19-nmr, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein nsp7. The 83 amino acid nsp7 protein is an essential cofactor in the RNA-dependent RNA polymerase. The polymerase activity and processivity of nsp12 are greatly enhanced by binding 1 copy of nsp7 and 2 copies of nsp8 to form a 160 kD complex. A separate hexadecameric complex of nsp7 and nsp8 (8 copies of each) forms a large ring-like structure. Thus, nsp7 is an important component of several large protein complexes that are required for replication of the large and complex coronavirus genome. We here report the near-complete NMR backbone and sidechain resonance assignment (1H,13C,15N) of isolated nsp7 from SARS-CoV-2 in solution. Further, we derive the secondary structure and compare it to the previously reported assignments and structure of the SARS-CoV nsp7.


Subject(s)
Coronavirus RNA-Dependent RNA Polymerase/chemistry , Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Carbon Isotopes , Genome, Viral , Hydrogen , Hydrogen-Ion Concentration , Nitrogen Isotopes , Protein Binding , Protein Domains , Protein Structure, Secondary
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119388, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1142229

ABSTRACT

Prospective antiviral molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide has been probed using Fourier transform infrared (FTIR), FT-Raman and quantum chemical computations. The geometry equilibrium and natural bond orbital analysis have been carried out with density functional theory employing Becke, 3-parameter, Lee-Yang-Parr method with the 6-311G++(d,p) basis set. The vibrational assignments pertaining to different modes of vibrations have been augmented by normal coordinate analysis, force constant and potential energy distributions. Drug likeness and oral activity have been carried out based on Lipinski's rule of five. The inhibiting potency of 2(2E)-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide has been investigated by docking simulation against SARS-CoV-2 protein. The optimized geometry shows a planar structure between the chromone and the side chain. Differences in the geometries due to the substitution of the electronegative atom and intermolecular contacts due to the chromone and hydrazinecarbothioamide were analyzed. NBO analysis confirms the presence of two strong stable hydrogen bonded NH⋯O intermolecular interactions and two weak hydrogen bonded CH⋯O interactions. The red shift in NH stretching frequency exposed from IR substantiates the formation of NH⋯O intermolecular hydrogen bond and the blue shift in CH stretching frequency substantiates the formation of CH⋯O intermolecular hydrogen bond. Drug likeness, absorption, distribution, metabolism, excretion and toxicity property gives an idea about the pharmacokinetic properties of the title molecule. The binding energy of the nonbonding interaction with Histidine 41 and Cysteine 145, present a clear view that 2(2E)-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide can irreversibly interact with SARS-CoV-2 protease.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Chromones , Coronavirus 3C Proteases/antagonists & inhibitors , Drugs, Investigational , SARS-CoV-2/drug effects , Thiourea , Antiviral Agents/analysis , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Chromones/analysis , Chromones/chemical synthesis , Chromones/chemistry , Chromones/pharmacokinetics , Computational Chemistry , Coronavirus 3C Proteases/metabolism , Crystallography, X-Ray , Drugs, Investigational/analysis , Drugs, Investigational/chemical synthesis , Drugs, Investigational/chemistry , Drugs, Investigational/pharmacokinetics , Humans , Hydrazines/chemistry , Hydrogen/chemistry , Hydrogen Bonding , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Protein Binding , Quantum Theory , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Thioamides/analysis , Thioamides/chemical synthesis , Thioamides/chemistry , Thioamides/pharmacokinetics , Thiourea/analysis , Thiourea/chemical synthesis , Thiourea/chemistry , Thiourea/pharmacokinetics , Vibration
17.
Chem Res Toxicol ; 34(4): 952-958, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1132015

ABSTRACT

Kawasaki disease (KD) is a systemic vasculitis and is the most commonly acquired heart disease among children in many countries, which was first reported 50 years ago in Japan. The 2019 coronavirus disease (COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has been a pandemic in most of the world since 2020, and since late 2019 in China. Kawasaki-like disease caused by COVID-19 shares some symptoms with KD, referred to as multisystem inflammatory syndrome in children, and has been reported in the United States, Italy, France, England, and other areas of Europe, with an almost 6-10 times or more increase compared with previous years of KD prevalence. Hydrogen gas is a stable and efficient antioxidant, which has a positive effect on oxidative damage, inflammation, cell apoptosis, and abnormal blood vessel inflammation. This review reports the chemical and biochemical aspects of hydrogen gas inhalation in treating KD and COVID-19.


Subject(s)
Antioxidants/therapeutic use , COVID-19/drug therapy , Hydrogen/therapeutic use , Mucocutaneous Lymph Node Syndrome/drug therapy , Antioxidants/chemistry , Antioxidants/pharmacology , COVID-19/pathology , COVID-19/virology , Cytokines/metabolism , Humans , Hydrogen/chemistry , Hydrogen/pharmacology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/pathology , Oxidative Stress/drug effects , Prevalence , SARS-CoV-2/isolation & purification
18.
Int J Mol Sci ; 22(5)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1125259

ABSTRACT

Mitochondria are the largest source of reactive oxygen species (ROS) and are intracellular organelles that produce large amounts of the most potent hydroxyl radical (·OH). Molecular hydrogen (H2) can selectively eliminate ·OH generated inside of the mitochondria. Inflammation is induced by the release of proinflammatory cytokines produced by macrophages and neutrophils. However, an uncontrolled or exaggerated response often occurs, resulting in severe inflammation that can lead to acute or chronic inflammatory diseases. Recent studies have reported that ROS activate NLRP3 inflammasomes, and that this stimulation triggers the production of proinflammatory cytokines. It has been shown in literature that H2 can be based on the mechanisms that inhibit mitochondrial ROS. However, the ability for H2 to inhibit NLRP3 inflammasome activation via mitochondrial oxidation is poorly understood. In this review, we hypothesize a possible mechanism by which H2 inhibits mitochondrial oxidation. Medical applications of H2 may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19/therapy , Hydrogen/pharmacology , Hydrogen/therapeutic use , Inflammation/therapy , Mitochondria/physiology , Animals , Chronic Disease , Humans , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism
19.
Biomol NMR Assign ; 15(1): 219-227, 2021 04.
Article in English | MEDLINE | ID: covidwho-1116314

ABSTRACT

The nucleocapsid protein N from SARS-CoV-2 is one of the most highly expressed proteins by the virus and plays a number of important roles in the transcription and assembly of the virion within the infected host cell. It is expected to be characterized by a highly dynamic and heterogeneous structure as can be inferred by bioinformatics analyses as well as from the data available for the homologous protein from SARS-CoV. The two globular domains of the protein (NTD and CTD) have been investigated while no high-resolution information is available yet for the flexible regions of the protein. We focus here on the 1-248 construct which comprises two disordered fragments (IDR1 and IDR2) in addition to the N-terminal globular domain (NTD) and report the sequence-specific assignment of the two disordered regions, a step forward towards the complete characterization of the whole protein.


Subject(s)
Coronavirus Nucleocapsid Proteins/chemistry , Magnetic Resonance Spectroscopy , SARS-CoV-2/chemistry , Carbon Isotopes , Computational Biology , Hydrogen , Nitrogen Isotopes , Phosphoproteins/chemistry , Protein Binding , Protein Domains , Protein Structure, Secondary
20.
Small ; 17(12): e2100139, 2021 03.
Article in English | MEDLINE | ID: covidwho-1114230

ABSTRACT

The novel coronavirus SARS-CoV-2 has prompted a worldwide pandemic and poses a great threat to public safety and global economies. Most present personal protective equipment (PPE) used to intercept pathogenic microorganisms is deficient in biocidal properties. Herein, we present green nanofibers with effective antibacterial and antiviral activities that can provide sustainable bioprotection by continuously producing reactive oxygen species (ROS). The superiority of the design is that the nanofibers can absorb and store visible light energy and maintain the activity under light or dark environment. Moreover, the nanofibers can uninterruptedly release ROS in the absence of an external hydrogen donor, acting as a biocide under all weather conditions. A facile spraying method is proposed to rapidly deploy the functional nanofibers to existing PPE, such as protective suits and masks. The modified PPE exhibit stable ROS production, excellent capacity for storing activity potential, long-term durability, and high bactericidal (>99.9%) and viricidal (>99.999%) efficacies.


Subject(s)
Anti-Infective Agents/pharmacology , Hydrogen/chemistry , Light , Nanofibers/chemistry , Benzophenones/chemistry , Cellulose/pharmacology , Nanofibers/ultrastructure , Riboflavin/pharmacology
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