Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
Molecules ; 27(12)2022 Jun 12.
Article in English | MEDLINE | ID: covidwho-1917634

ABSTRACT

Inflammation is a severe topic in the immune system and play a role as pro-inflammatory mediators. In response to such inflammatory substances, immune cells release cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Lipopolysaccharide (LPS) is known as an endotoxin in the outer membrane of Gram-negative bacteria, and it catalyzes inflammation by stimulating the secretion of inflammatory-mediated cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by stimulated immune cells. Among the pathways involved in inflammation, nuclear factor kappa (NF-кB) and mitogen-activated protein kinases (MAPKs) are important. NF-kB is a diploid composed of p65 and IkBα and stimulates the pro- gene. MAPKs is a family consisting of the extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, JNK and p38 play a role as proinflammatory mediators. Thus, we aim to determine the scutellarein (SCU) effect on LPS stimulated RAW264.7 cells. Furthermore, since scutellarein has been shown to inhibit the SARS coronavirus helicase and has been used in Chinese medicine to treat inflammatory disorders like COVID-19, it would be required to examine scutellarein's anti-inflammatory mechanism. We identified inflammation-inducing substances using western blot with RAW264.7 cells and SCU. And we discovered that was reduced by treatment with SCU in p-p65 and p-IκBα. Also, we found that p-JNK and p-ERK were also decreased but there was no effect in p-p38. In addition, we have confirmed that the iNOS was also decreased after treatment but there is no change in the expression of COX-2. Therefore, this study shows that SCU can be used as a compound to treat inflammation.


Subject(s)
COVID-19 , NF-kappa B , Animals , Apigenin , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides/adverse effects , Mice , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Signal Transduction
2.
Molecules ; 27(11)2022 May 29.
Article in English | MEDLINE | ID: covidwho-1892925

ABSTRACT

Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars (2-3) and ribonucleoside analogs (4-8) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2, 7, and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6.


Subject(s)
Antineoplastic Agents , Nucleosides , Analgesics/chemistry , Animals , Antineoplastic Agents/chemistry , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , HeLa Cells , Humans , Mice , Molecular Docking Simulation , Molecular Structure , Nucleosides/pharmacology , Structure-Activity Relationship , Sugars
3.
Molecules ; 27(9)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1847380

ABSTRACT

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9-17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and bioactive disubstituted compound encompasses one electron-withdrawing methyl and one electron-donating fluoro groups in one arene. COX-2 is selective but not COX-2 to bioactive compounds that contain both two electron-withdrawing groups; disubstituted analogs with both resonance-formable electron-donating dihydroxy groups display high COX-2 activity but inferior COX-2 selectivity. In silico simulation and modeling for three COX-2 active-p-fluoro, p-hydroxy and p-amino-fenbufens show a preferable docking to COX-2 than COX-1. The most stabilization by the p-hydroxy fenbufen with COX-2 predicted by theoretical simulation is consistent with its prominent COX-2 inhibition resulting from experiments.


Subject(s)
Cyclooxygenase 2 Inhibitors , Drug Design , Anti-Inflammatory Agents/pharmacology , Biological Assay , Cyclooxygenase 1 , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/pharmacology , Molecular Docking Simulation , Molecular Structure , Phenylbutyrates , Structure-Activity Relationship
4.
Int J Mol Sci ; 23(4)2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1715398

ABSTRACT

The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.


Subject(s)
Anhedonia/physiology , Cyclooxygenase 2/metabolism , Hippocampus/metabolism , Stress, Psychological/metabolism , Anhedonia/drug effects , Animals , Antidepressive Agents/pharmacology , Celecoxib/pharmacology , Citalopram/pharmacology , Depression/drug therapy , Depression/metabolism , Hindlimb Suspension/physiology , Hippocampus/drug effects , Male , Mice , Mice, Inbred C57BL , Rats , Rats, Wistar , Serotonin Uptake Inhibitors/pharmacology , Stress, Psychological/drug therapy , Swimming/physiology
5.
Int Immunopharmacol ; 104: 108502, 2022 03.
Article in English | MEDLINE | ID: covidwho-1641351

ABSTRACT

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.


Subject(s)
COVID-19/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Child , Cyclooxygenase 2/blood , Cyclooxygenase 2/metabolism , Female , Glial Fibrillary Acidic Protein/blood , Glial Fibrillary Acidic Protein/metabolism , HMGB1 Protein/blood , HMGB1 Protein/metabolism , Healthy Volunteers , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation/immunology , Inflammation/virology , Male , Middle Aged , Oxidative Stress/immunology , Receptor for Advanced Glycation End Products/blood , Receptor for Advanced Glycation End Products/metabolism , SARS-CoV-2/immunology , Severity of Illness Index , Up-Regulation/immunology , Young Adult
6.
Bioorg Chem ; 117: 105466, 2021 12.
Article in English | MEDLINE | ID: covidwho-1499653

ABSTRACT

Series of piperidone-salicylate conjugates were synthesized through the reaction of 3E,5E-bis(arylidene)-4-piperidones with the appropriate acid chloride of acetylsalicylate in the presence of triethylamine. All the synthesized conjugates reveal antiproliferative properties against A431 (squamous skin) cancer cell line with potency higher than that of 5-fluorouracil. Many of the synthesized agents also exhibit promising antiproliferative properties against HCT116 (colon) cancer cell line, of which 5o and 5c are the most effective with 12.9, 9.8 folds potency compared with Sunitinib. Promising activity is also shown against MCF7 (breast) cancer cell line with 1.19, 1.12 folds relative to 5-fluorouracil. PI-flow cytometry of compound 5c supports the arrest of cell cycle at G1-phase. However, compound 5o and Sunitinib arrest the cell cycle at S-phase. The synthesized conjugates can be considered as multi-targeted tyrosine kinase inhibitors due to the promising properties against VEGFR-2 and EGFR in MCF7 and HCT116. CDOCKER studies support the EGFR inhibitory properties. Compounds 5p and 5i possessing thienylidene heterocycle are anti-SARS-CoV-2 with high therapeutic indices. Many of the synthesized agents show enhanced COX-1/2 properties than aspirin with better selectivity index towards COX-2 relative to COX-1. The possible applicability of the potent candidates discovered as antitumor and anti-SARS-CoV-2 is supported by the safe profile against normal (non-cancer, RPE1 and VERO-E6) cells.


Subject(s)
Antineoplastic Agents/chemistry , Antiviral Agents/chemistry , Aspirin/chemistry , Curcumin/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , COVID-19/pathology , COVID-19/virology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cyclooxygenase 1/chemistry , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/chemistry , Cyclooxygenase 2/metabolism , Drug Design , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Protein Binding , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/metabolism
7.
Sci Rep ; 11(1): 19752, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454813

ABSTRACT

Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.


Subject(s)
COVID-19/pathology , Disease Susceptibility , Metabolic Syndrome/pathology , Animals , Blood Coagulation Factors/genetics , Blood Coagulation Factors/metabolism , COVID-19/complications , COVID-19/virology , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Diet, High-Fat/veterinary , Disease Models, Animal , Humans , Immunity, Innate/genetics , Metabolic Syndrome/complications , Metabolic Syndrome/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Myocardium/metabolism , Oxidative Stress/genetics , Platelet Aggregation , Receptors, Purinergic P2Y1/genetics , Receptors, Purinergic P2Y1/metabolism , Renin-Angiotensin System , Risk Factors , SARS-CoV-2/isolation & purification , Swine , Urokinase-Type Plasminogen Activator/genetics , Urokinase-Type Plasminogen Activator/metabolism
8.
Cells ; 10(9)2021 08 25.
Article in English | MEDLINE | ID: covidwho-1374305

ABSTRACT

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.


Subject(s)
COVID-19/genetics , COVID-19/virology , Cellular Senescence/genetics , Gene Expression Profiling , Neurons/pathology , Oxidative Stress/genetics , SARS-CoV-2/physiology , Caspase 3/metabolism , Cell Death , Cell Line , Cyclooxygenase 2/metabolism , Humans , Superoxide Dismutase/metabolism , Virus Replication/physiology
9.
Int J Mol Sci ; 21(22)2020 Nov 10.
Article in English | MEDLINE | ID: covidwho-917002

ABSTRACT

Pro-inflammatory cytokines like interleukin-1ß (IL-1ß) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1ß on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1ß and used Atomic Force Microscopy to unveil that IL-1ß significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1ß stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1ß may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1ß-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1ß provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.


Subject(s)
Interleukin-1beta/physiology , Lung/physiology , Actins/metabolism , Adolescent , Adult , Biomechanical Phenomena , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cells, Cultured , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type III/genetics , Collagen Type III/metabolism , Cyclooxygenase 2/metabolism , Elasticity/drug effects , Elasticity/physiology , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/physiology , Humans , Interleukin-1beta/pharmacology , Lung/cytology , Lung/drug effects , Male , Microscopy, Atomic Force , RNA, Messenger/genetics , RNA, Messenger/metabolism , Regeneration/genetics , Regeneration/physiology , Wound Healing/drug effects , Wound Healing/genetics , Wound Healing/physiology , Young Adult
10.
J Immunol ; 206(2): 329-334, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-961742

ABSTRACT

The COVID-19 pandemic has affected more than 20 million people worldwide, with mortality exceeding 800,000 patients. Risk factors associated with severe disease and mortality include advanced age, hypertension, diabetes, and obesity. Each of these risk factors pathologically disrupts the lipidome, including immunomodulatory eicosanoid and docosanoid lipid mediators (LMs). We hypothesized that dysregulation of LMs may be a defining feature of the severity of COVID-19. By examining LMs and polyunsaturated fatty acid precursor lipids in serum from hospitalized COVID-19 patients, we demonstrate that moderate and severe disease are separated by specific differences in abundance of immune-regulatory and proinflammatory LMs. This difference in LM balance corresponded with decreased LM products of ALOX12 and COX2 and an increase LMs products of ALOX5 and cytochrome p450. Given the important immune-regulatory role of LMs, these data provide mechanistic insight into an immuno-lipidomic imbalance in severe COVID-19.


Subject(s)
COVID-19 , Eicosanoids , Lipidomics , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Arachidonate 12-Lipoxygenase/immunology , Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 5-Lipoxygenase/immunology , Arachidonate 5-Lipoxygenase/metabolism , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , Cyclooxygenase 2/immunology , Cyclooxygenase 2/metabolism , Eicosanoids/blood , Eicosanoids/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
11.
Sci Immunol ; 5(51)2020 09 17.
Article in English | MEDLINE | ID: covidwho-781081

ABSTRACT

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunity, Innate , Monocytes/immunology , Pneumonia, Viral/immunology , Adult , Aged , Biomarkers/blood , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Cyclooxygenase 2/immunology , Cyclooxygenase 2/metabolism , Disease Progression , Female , Host Microbial Interactions/immunology , Humans , Inflammation Mediators/blood , Inflammation Mediators/immunology , Ki-67 Antigen/immunology , Ki-67 Antigen/metabolism , Longitudinal Studies , Male , Middle Aged , Monocytes/metabolism , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , United Kingdom/epidemiology
12.
Sci Rep ; 10(1): 10187, 2020 06 23.
Article in English | MEDLINE | ID: covidwho-613136

ABSTRACT

Microsomal prostaglandin E2 synthase-1 (mPGES-1) is known as an ideal target for next generation of anti-inflammatory drugs without the side effects of currently available anti-inflammatory drugs. However, there has been no clinically promising mPGES-1 inhibitor identified through traditional drug discovery and development route. Here we report a new approach, called DREAM-in-CDM (Drug Repurposing Effort Applying Integrated Modeling-in vitro/vivo-Clinical Data Mining), to identify an FDA-approved drug suitable for use as an effective analgesic targeting mPGES-1. The DREAM-in-CDM approach consists of three steps: computational screening of FDA-approved drugs; in vitro and/or in vivo assays; and clinical data mining. By using the DREAM-in-CDM approach, lapatinib has been identified as a promising mPGES-1 inhibitor which may have significant anti-inflammatory effects to relieve various forms of pain and possibly treat various inflammation conditions involved in other inflammation-related diseases such as the lung inflammation caused by the newly identified COVID-19. We anticipate that the DREAM-in-CDM approach will be used to repurpose FDA-approved drugs for various new therapeutic indications associated with new targets.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Coronavirus Infections/drug therapy , Drug Repositioning , Lapatinib/pharmacology , Pneumonia, Viral/drug therapy , Prostaglandin-E Synthases/antagonists & inhibitors , Betacoronavirus , COVID-19 , Computational Chemistry/methods , Coronavirus Infections/pathology , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase Inhibitors/pharmacology , Humans , Inflammation/drug therapy , Molecular Dynamics Simulation , Pandemics , Pneumonia, Viral/pathology , Prostaglandin-E Synthases/metabolism , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL