Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system.


: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.


Pharmacol Res


Pharmacological research


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 KY




Has Abstract


2020-09-01 00:00:00












  • Nerve growth factor enhances cough via a central mechanism of action.

    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


    authors: El-Hashim AZ,Jaffal SM,Al-Rashidi FT,Luqmani YA,Akhtar S

    更新日期:2013-08-01 00:00:00

  • NGF and heart: Is there a role in heart disease?

    abstract::The review emphasizes the role of NGF, the most representative member of the neurotrophins family, in cardiac physiopathology with a particular focus on healing and sprouting processes occurring after tissue damage. Cardiac and circulating NGF levels dramatically increase following myocardial injury (MI). A very early...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Govoni S,Pascale A,Amadio M,Calvillo L,D'Elia E,Cereda C,Fantucci P,Ceroni M,Vanoli E

    更新日期:2011-04-01 00:00:00

  • Differential in vivo and in vitro effect of gentamicin on glutamate synthesis and glutamate deamination in rabbit kidney-cortex tubules and mitochondria.

    abstract::The effect of gentamicin on both glutamate synthesis and glutamate deamination was studied in kidney-cortex mitochondria and tubules isolated from both control and gentamicin-treated animals. In kidney-cortex mitochondria which were permeabilized in order to make a free access of substrates and antibiotic to the gluta...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Bryła J,Lietz T,Jarzyna R,Michalik M,Pietkiewicz J

    更新日期:1992-12-01 00:00:00

  • Assessment of resveratrol, apocynin and taurine on mechanical-metabolic uncoupling and oxidative stress in a mouse model of duchenne muscular dystrophy: A comparison with the gold standard, α-methyl prednisolone.

    abstract::Antioxidants have a great potential as adjuvant therapeutics in patients with Duchenne muscular dystrophy, although systematic comparisons at pre-clinical level are limited. The present study is a head-to-head assessment, in the exercised mdx mouse model of DMD, of natural compounds, resveratrol and apocynin, and of t...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Capogrosso RF,Cozzoli A,Mantuano P,Camerino GM,Massari AM,Sblendorio VT,De Bellis M,Tamma R,Giustino A,Nico B,Montagnani M,De Luca A

    更新日期:2016-04-01 00:00:00

  • The effects of doxazosin on plasma lipid and lipoprotein levels in hypertensive patients.

    abstract::Plasma lipid and lipoprotein levels were evaluated in 27 adults with essential hypertension at four different periods during a 12-month treatment with doxazosin. Mean plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDLC), triglyceride (TG), very low density lipoprotein-cholesterol (VLDLC) and the L...

    journal_title:Pharmacological research

    pub_type: 临床试验,杂志文章


    authors: Ahaneku JE,Taylor GO,Agbedana EO,Walker O,Salako LA

    更新日期:1994-10-01 00:00:00

  • Candidate drugs against SARS-CoV-2 and COVID-19.

    abstract::Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infect...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: McKee DL,Sternberg A,Stange U,Laufer S,Naujokat C

    更新日期:2020-07-01 00:00:00

  • Pharmacological, non-pharmacological and stem cell therapies for the management of autism spectrum disorders: A focus on human studies.

    abstract::In the last decade, the prevalence of autism spectrum disorders (ASD) has dramatically escalated worldwide. Currently available drugs mainly target some co-occurring symptoms of ASD, but are not effective on the core symptoms, namely impairments in communication and social interaction, and the presence of restricted a...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Pistollato F,Forbes-Hernández TY,Calderón Iglesias R,Ruiz R,Elexpuru Zabaleta M,Cianciosi D,Giampieri F,Battino M

    更新日期:2020-02-01 00:00:00

  • Therapeutics in pediatric diabetes: insulin and non-insulin approaches. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

    abstract::Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analog...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Kim J,Kim SM,Nguyen HC,Redondo MJ

    更新日期:2012-01-01 00:00:00

  • Evaluation of beta-endorphin/beta-lipotropin immunoreactivity content in the CSF of patients affected by deafferentation pain syndromes.

    abstract::Beta-endorphin/beta-lipotropin immunoreactivity (BE/BLPH-IR) content was evaluated in the CSF of patients suffering by deafferentation pain syndromes. BE/BLPH-IR CSF concentrations of these patients were compared with those obtained in a group of patients affected by low back pain and in a control group without pain p...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Salar G,Alessio L,Govoni S,Battaini F,Iob I,Goss I,Trabucchi M

    更新日期:1991-02-01 00:00:00

  • Lipocalin-2 and iron trafficking in the tumor microenvironment.

    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


    authors: Jung M,Mertens C,Bauer R,Rehwald C,Brüne B

    更新日期:2017-06-01 00:00:00

  • Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway.

    abstract::Echinomycin, in typical DNA minor groove binder, had comparable efficacy compared to 5-FU in the phase II trail of colon cancer treatment. To improve echinomycin's drawback (hydrophobicity, toxicity), we synthesized the YK-2000 series (echinomycin analogues). Among these, YK-2000 had the best in vitro cytotoxicity on ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Park JY,Park SJ,Shim KY,Lee KJ,Kim YB,Kim YH,Kim SK

    更新日期:2004-08-01 00:00:00

  • Peripheral FAAH inhibition causes profound antinociception and protects against indomethacin-induced gastric lesions.

    abstract::Fatty-acid amide hydrolase (FAAH) catalyzes the intracellular hydrolysis of the endocannabinoid anandamide and other bioactive lipid amides. In the present study, we conducted a comparative characterization of the effects of the newly identified brain-impermeant FAAH inhibitor, URB937 ([3-(3-carbamoylphenyl)-4-hydroxy...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Sasso O,Bertorelli R,Bandiera T,Scarpelli R,Colombano G,Armirotti A,Moreno-Sanz G,Reggiani A,Piomelli D

    更新日期:2012-05-01 00:00:00

  • A preliminary evaluation of antifertility activity of a triterpenoid glycoside (DSS) from Dalbergia saxatilis in female Wistar rats.

    abstract::Antifertility activity of a triterpenoid glycoside, DSS, isolated from the root of Dalbergia saxatilis was investigated in female Wistar rats of breeding age. When administered by gastric intubation at a dose rate of 200 mg kg(-1)body weight at the premating period, conception was inhibited in 71.4% of the treated ani...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Uchendu CN,Kamalu TN,Asuzu IU

    更新日期:2000-05-01 00:00:00

  • Blockade of the p38 mitogen-activated protein kinase pathway inhibits inducible nitric oxide synthase and interleukin-6 expression in MC3T3E-1 osteoblasts.

    abstract::Treatment of MC3T3E-1 osteoblast cultures with combined interferon- gamma(IFN- gamma), lipopolysaccharide (LPS) and tumor necrosis factor- alpha(TNF- alpha) induces expressions of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), resulting in sustained releases of large amounts of nitric oxide and IL-6....

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Chae HJ,Kim SC,Chae SW,An NH,Kim HH,Lee ZH,Kim HR

    更新日期:2001-03-01 00:00:00

  • Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy.

    abstract::Most solid tumor cells adapt to their heterogeneous microenvironment by depending largely on aerobic glycolysis for energy production, a phenomenon called the Warburg effect, which is a hallmark of cancer. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generate essen...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Abdel-Wahab AF,Mahmoud W,Al-Harizy RM

    更新日期:2019-12-01 00:00:00

  • Exogenous insulin-like growth factor (IGF)-1 improves the impaired healing of gastric mucosal lesions in diabetic rats.

    abstract:BACKGROUND:We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. METHODS:Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Korolkiewicz RP,Tashima K,Fujita A,Kato S,Takeuchi K

    更新日期:2000-02-01 00:00:00

  • Advances into Understanding the Vital Role of the Mitochondrial Citrate Carrier (CIC) in Metabolic Diseases.

    abstract::The mitochondrial citrate carrier (CIC) is a nuclear-encoded protein located in the inner mitochondrial membrane. By mediating efflux of citrate from the mitochondria to the cytosol, CIC links mitochondrial central carbon metabolism and cytosolic lipogenesis together. Abnormal activity or expression of CIC was found i...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Peng R,Zhang M,Wang H,Lin J,Wang H,Wang F,Liu L,Zhao Q,Liu J

    更新日期:2020-11-01 00:00:00

  • Pharmacokinetic and chemoprevention studies on tea in humans.

    abstract::Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolit...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Chow HH,Hakim IA

    更新日期:2011-08-01 00:00:00

  • The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endotheli

    abstract::Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. inc...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Martelli A,Testai L,Anzini M,Cappelli A,Di Capua A,Biava M,Poce G,Consalvi S,Giordani A,Caselli G,Rovati L,Ghelardini C,Patrignani P,Sautebin L,Breschi MC,Calderone V

    更新日期:2013-12-01 00:00:00

  • Role of heterogeneous regulatory T cells in the tumor microenvironment.

    abstract::Regulatory T cells (Tregs) modulate ongoing immune responses to prevent autoimmunity in healthy bodies and inhibit effective anti-tumor immunity responses in tumor patients, leading to tumor progression. The function of Tregs in tumor immunity suggests that elimination of Tregs in the host may enhance the anti-tumor i...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Wei T,Zhong W,Li Q

    更新日期:2020-03-01 00:00:00

  • Mechanisms underlying the losartan treatment-induced improvement in the endothelial dysfunction seen in mesenteric arteries from type 2 diabetic rats.

    abstract::It is well known that type 2 diabetes mellitus is frequently associated with vascular dysfunction and an elevated systemic blood pressure, yet the underlying mechanisms are not completely understood. We previously reported that in mesenteric arteries from established type 2 diabetic Otsuka Long-Evans Tokushima fatty (...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Matsumoto T,Ishida K,Nakayama N,Taguchi K,Kobayashi T,Kamata K

    更新日期:2010-09-01 00:00:00

  • A pharmacological assessment of agonists and modulators at α4β2γ2 and α4β2δ GABAA receptors: The challenge in comparing apples with oranges.

    abstract::Extrasynaptically located γ-aminobutyric acid (GABA) receptors type A are often characterized by the presence of a δ subunit in the receptor complex. δ-Containing receptors respond to low ambient concentrations of GABA, or respond to spillover of GABA from the synapse, and give rise to tonic inhibitory currents. In ce...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Ahring PK,Bang LH,Jensen ML,Strøbæk D,Hartiadi LY,Chebib M,Absalom N

    更新日期:2016-09-01 00:00:00

  • MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1.

    abstract::As one classic anticancer drug, clinical application of Doxorubicin (Dox) is limited due to its side effects. In our previous work, we have investigated the drug targets to treat Dox-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. In this paper, the mechanisms and new drug-target associated with Dox-induced...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Zhao X,Jin Y,Li L,Xu L,Tang Z,Qi Y,Yin L,Peng J

    更新日期:2019-08-01 00:00:00

  • DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.

    abstract::We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, an...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Oana F,Homma T,Takeda H,Matsuzawa A,Akahane S,Isaji M,Akahane M

    更新日期:2005-11-01 00:00:00

  • The role of small molecule Flt3 receptor protein-tyrosine kinase inhibitors in the treatment of Flt3-positive acute myelogenous leukemias.

    abstract::Flt3 is expressed by early myeloid and lymphoid progenitor cells and it regulates the proliferation and differentiation of hematopoietic cells. Flt3 is activated by the Flt3 ligand, the monomeric form of which is a polypeptide of about 200 amino acid residues. Both membrane-associated and soluble Flt3 ligands, which a...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Roskoski R Jr

    更新日期:2020-05-01 00:00:00

  • Cost-effective pharmacological prevention of acute coronary syndromes.

    abstract::The growing size of trials on primary and secondary prevention of acute coronary syndromes characterised by very broad inclusion criteria may seem logical to 'trialists', who reason that the the broader the inclusion criteria, the easier it is to recruit large numbers of patients in a short period of time and the more...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Monaco C,Cianflone D,Summaria F,Maseri A,Crea F

    更新日期:1998-06-01 00:00:00

  • Back to the heart: the protective role of adiponectin.

    abstract::Cardiovascular disease (CVD) is the leading cause of death worldwide and the prevalence of obesity and diabetes are increasing. In obesity, adipose tissue increases the secretion of bioactive mediators (adipokines) that may represent a key mechanism linking obesity to CVD. Adiponectin, extensively studied in metabolic...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Caselli C,D'Amico A,Cabiati M,Prescimone T,Del Ry S,Giannessi D

    更新日期:2014-04-01 00:00:00

  • Lipid-regulating properties of butyric acid and 4-phenylbutyric acid: Molecular mechanisms and therapeutic applications.

    abstract::In the past two decades, significant advances have been made in the etiology of lipid disorders. Concomitantly, the discovery of liporegulatory functions of certain short-chain fatty acids has generated interest in their clinical applications. In particular, butyric acid (BA) and its derivative, 4-phenylbutyric acid (...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: He B,Moreau R

    更新日期:2019-06-01 00:00:00

  • Antitumor activities and pharmacokinetics of silatecans DB-67 and DB-91.

    abstract::DB-67 and its lactone homolog DB-91 are derivatives of topoisomerase I inhibitor camptothecin (CPT) with silyl moiety, which may exhibit a slower inactivation process by changed kinetics of protein binding and/or hydrolysis of its lactone ring and result in increased antitumor activity and decreased toxicity. Pharmaco...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Yeh TK,Li CM,Chen CP,Chuu JJ,Huang CL,Wang HS,Shen CC,Lee TY,Chang CY,Chang CM,Chao YS,Lin CT,Chang JY,Chen CT

    更新日期:2010-02-01 00:00:00

  • Lipocortin and vasocortin: two species of anti-inflammatory proteins mimicking the effects of glucocorticoids.

    abstract::The anti-inflammatory effect of glucocorticoids depends, at least in part, on the induction of two regulatory proteins, lipocortin and vasocortin, both preventing the release of inflammatory mediators. Lipocortin inhibits phospholipase A2 (PLA2) and therefore reduces arachidonic acid metabolites formation. Vasocortin ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Sautebin L,Carnuccio R,Ialenti A,Di Rosa M

    更新日期:1992-01-01 00:00:00