Abstract：
:Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 μM). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Yuan S,Chan JFW,Chik KKH,Chan CCY,Tsang JOL,Liang R,Cao J,Tang K,Chen LL,Wen K,Cai JP,Ye ZW,Lu G,Chu H,Jin DY,Yuen KYdoi
10.1016/j.phrs.2020.104960subject
Has Abstractpub_date
2020-09-01 00:00:00pages
104960eissn
1043-6618issn
1096-1186pii
S1043-6618(20)31268-8journal_volume
159pub_type
杂志文章abstract：:The pharmacological physiological effects of the endogenous cannabinomimetic (endocannabinoid) anandamide have been well characterized. Another endocannabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2-AG occurs in vertebrate and invertebrate tissues and binds to both cannabinoid receptors (CB1 ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0702
更新日期：2000-10-01 00:00:00
abstract：:We compared the protective abilities of Mangifera indica L. stem bark extract (Vimang) 50-250 mgkg(-1), mangiferin 50 mgkg(-1), vitamin C 100 mgkg(-1), vitamin E 100 mgkg(-1)and beta -carotene 50 mgkg(-1)against the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative damage in serum, liver, brain as well as i...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0727
更新日期：2000-12-01 00:00:00
abstract：:Cardiovascular baroreflex mechanisms and sympathetic tone could be involved in the arterial hypertension by coarctation of abdominal aorta artery (CoA). The present work analyzes the effect on the arterial pressure and heart rate (HR) of the clonidine, an alpha(2)-adrenergic central acting antihypertensive agent, afte...
journal_title：Pharmacological research
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doi：
更新日期：2003-07-01 00:00:00
abstract：:Radiotherapy plays a critical role in the treatment of non-small cell lung cancer (NSCLC). However, radioresistance is a major barrier against increasing the efficiency of radiotherapy for NSCLC. To understand the mechanisms underlying NSCLC radioresistance, we previously focused on the potential involvement of PIM1, ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.01.005
更新日期：2013-04-01 00:00:00
abstract：:The possible involvement of adenosine 5'-triphosphate (ATP) receptors in the function of the hippocampus is reviewed. The involvement of these receptors in the hippocampus is suggested by data that ATP is released from hippocampal slices [1] and that it also induces fast synaptic currents in cultured hippocampal neuro...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1998.0382
更新日期：1998-11-01 00:00:00
abstract：:Local microcirculatory dysfunction within the pancreatic gland might be an important factor in the conversion of oedematous to necrotizing pancreatitis. Therapeutic agents, improving the pancreatic blood flow, might be valuable in acute pancreatitis treatment. An influence of nitric oxide, heparin and procaine treatme...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0200
更新日期：1997-08-01 00:00:00
abstract：:In spite of continuous research in the field of bronchial asthma, still no satisfactory drug is available. Recently a new class of oligopeptide exhibited antiallergic activity by inhibiting the synthesis of IgE antibody. The analogue of ADSDGK (94-335) has shown antiallergic activity in experimental models. The 94-335...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1998.0302
更新日期：1998-05-01 00:00:00
abstract：:Male weanling Wistar rats were fed a 4% cholestyramine diet and used as a model to demonstrate that a reduction in serum low density lipoproteins stimulates de novo cholesterogenesis leading to DNA synthesis and cell proliferation. Feeding this diet resulted in a decrease in serum very low density lipoproteins and low...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(89)90195-3
更新日期：1989-09-01 00:00:00
abstract：:Biotechnologicals are an invaluable resource in the treatment of patients with inflammatory rheumatic diseases (IRD) non-responsive or intolerant to conventional therapies. However, they are the main driver for increase in direct costs and represent a significant economic burden to healthcare systems worldwide. Since ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104467
更新日期：2019-11-01 00:00:00
abstract：:Idiopathic pulmonary fibrosis (IPF) is a debilitating condition where excess collagen deposition occurs in the extracellular matrix. At first sight, it is expected that the level of different kinds of matrix metalloproteinases might be downregulated in IPF as it is a matrix degrading collagenase. However, the role of ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104591
更新日期：2020-02-01 00:00:00
abstract：:Iron is an essential element for virtually all organisms. It facilitates cell proliferation and growth but also contributes to major hallmarks of cancer such as tumor initiation, growth, and metastasis. Often, iron handling of tumor cells is disturbed, with altered iron acquisition, efflux, and storage. Targeting pert...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.03.018
更新日期：2017-06-01 00:00:00
abstract：:Our preliminary data suggested that 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene [Viale M, Ottone M, Chiavarina B, Mariggiò MA, Prevosto C, Dell'Erba C, et al. Preliminary evaluation in vitro of the inhibition of cell proliferation, cytotoxicity and induction of apoptosis by 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadi...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2005.03.011
更新日期：2005-09-01 00:00:00
abstract：:TNF-related apoptosis-inducing ligand (TRAIL) selectively induces the apoptosis pathway in tumor cells leading to tumor cell death. Because TRAIL induction can kill tumor cells, cancer researchers have developed many agents to target TRAIL and some of these agents have entered clinical trials in oncology. Unfortunatel...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104716
更新日期：2020-05-01 00:00:00
abstract：:The DNA microarrays have proven to be a state of the art technique for high throughput comprehensive analysis of thousand of genes in parallel. The application of a DNA microarray to compare normal and pathological cells, tissues or organs may allow, along with classical positional cloning techniques, to speed up the ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2003.06.001
更新日期：2004-04-01 00:00:00
abstract：:The insulinotropic action of several new esters of succinic acid was assessed in isolated rat islets incubated in the presence of 7 mM D-glucose. An efficient secretory response was observed with the monobenzyl, monoisopropyl, monoallyl, monopropyl, monoethyl, monobutyl, dibutyl, dipropyl and diallyl esters of succini...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0038
更新日期：1996-04-01 00:00:00
abstract：:ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax) are under intensive preclinical and clinical investigation as treatments for hematologic and other malignancies. These small molecules mimic pro-death B-cell lymphoma-2 (Bcl-2) Homology 3 (BH3) domain-only proteins. They also bear a structural resemblance to certa...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.01.040
更新日期：2019-04-01 00:00:00
abstract：:It is a consensus view that a strategy to increase heart resistance to ischaemia-reperfusion is a warranted. Here, based on our previous study, we have hypothesized that a nicotinamide-rich diet could increase myocardial resistance to ischaemia-reperfusion. Therefore, the purpose of this study was to determine whether...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2010.01.008
更新日期：2010-06-01 00:00:00
abstract：:The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by re...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.05.003
更新日期：2013-08-01 00:00:00
abstract：:HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2014.06.011
更新日期：2014-10-01 00:00:00
abstract：:The insulinotropic action of the meglitinide analogues KAD-1229, A-4166 and repaglinide was examined in rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of nutrient secretagogues such as D-glucose and the methyl esters of pyruvic acid, succinic acid and glutamic acid. The meglitinide a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0026
更新日期：1996-03-01 00:00:00
abstract：:The effect of chloroquine and other antimalarial drugs on glutamate dehydrogenase activity was studied in liver and renal mitochondria as well as in kidney-cortex tubules of rabbit. In permeabilized mitochondria, with free access of substrates and drugs to glutamate dehydrogenase, 100 microns chloroquine decreased bot...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0108
更新日期：1997-01-01 00:00:00
abstract：:Oxaceprol, an established therapeutic agent for osteoarthritis, had no effect on macrophage prostaglandin E2 release in vitro and inhibited carrageenan paw oedema at high doses (18-150 mg/kg p.o.). In the same dose range, oxaceprol was comparable to indomethacin (3 mg/kg p.o.) as an inhibitor of yeast hyperalgaesia an...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0051
更新日期：1996-06-01 00:00:00
abstract：:We have studied the effect of acute trazodone (3--20 mg kg(-1)) and quipazine (1--3 mg kg(-1)) treatment on the apomorphine-induced (1 mg kg(-1), once daily over 2 weeks) aggressive behaviour in male Wistar rats. All doses of trazodone and quipazine tested attenuated the aggressiveness as evidenced by the abolished in...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0790
更新日期：2001-04-01 00:00:00
abstract：:The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibite...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1998.0398
更新日期：1998-12-01 00:00:00
abstract：:In this study, we have addressed the pharmacogenomic basis of the response of gastrointestinal tumors to six anticancer drugs using a panel of fifteen cell lines derived from pancreatic, stomach and biliary tract cancers. We determined the constitutive expression levels of 96 genes, whose encoded proteins contribute t...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.09.007
更新日期：2016-11-01 00:00:00
abstract：:Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2006.09.009
更新日期：2007-01-01 00:00:00
abstract：:Green tea (Camellia sinensis, Theaceace) is the second most popular beverage in the world and has been extensively studied for its putative disease preventive effects. Green tea is characterized by the presence of a high concentrations of polyphenolic compounds known as catechins, with (-)-epigallocatechin-3-gallate (...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2010.12.013
更新日期：2011-08-01 00:00:00
abstract：:Extensive studies have reported the significant roles of numerous cellular features and processes in properly maintaining neuronal morphology and function throughout the lifespan of an animal. Any alterations in their homeostasis appear to be strongly associated with neuronal aging and the pathogenesis of various neur...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.02.003
更新日期：2017-05-01 00:00:00
abstract：:Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-p...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104954
更新日期：2020-09-01 00:00:00
abstract：:In hypothermic rats with acute hypertension induced by intravenous injection of adrenalin, regional changes in blood-brain barrier permeability to macromolecules were investigated using Evans blue as indication. Evans blue albumin extravasation was determined as a macroscopic finding and a quantitative estimation with...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
