Abstract：
:The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (Mpro), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for Mpro, we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against Mpro. In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed to subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the Mpro catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.
journal_name
Life Scijournal_title
Life sciencesauthors
Hage-Melim LIDS,Federico LB,de Oliveira NKS,Francisco VCC,Correia LC,de Lima HB,Gomes SQ,Barcelos MP,Francischini IAG,da Silva CHTPdoi
10.1016/j.lfs.2020.117963subject
Has Abstractpub_date
2020-09-01 00:00:00pages
117963eissn
0024-3205issn
1879-0631pii
S0024-3205(20)30713-Xjournal_volume
256pub_type
杂志文章相关文献
LIFE SCIENCES文献大全abstract：:Female white-footed mice (Peromyscus leucopus) were injected twice daily with 5, 10, 50, 100 micrograms melatonin (MEL) or saline. Injections were given for 7 weeks at 2 and 12 hours after lights-on under a long day (LD 16:8) photoperiod. Afternoon administration of MEL induced gonadal regression, although a dose of 5...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(85)90549-1
更新日期：1985-08-26 00:00:00
abstract：:Methodological shortcomings present in elicitation of male sexual reflexes in anesthetized animals. The present study has demonstrated, however, that intraperitoneal (i.p.) injection of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, elicited simultaneously both penile erection and ejaculation in anes...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(00)00895-x
更新日期：2000-11-10 00:00:00
abstract：:Although intraepithelial T lymphocytes of the large intestine (LI) are known to differ from those of the small intestine (SI) in phenotype and function, differences in LI and SI lamina propria (LP) lymphocyte populations have not been clearly established. In this work we found striking phenotypic differences between S...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2004.08.042
更新日期：2005-04-29 00:00:00
abstract：:Normal mammary gland growth and reproduction were examined in C3H/HeMei mice given caffeine as drinking water (500 mg/l tap water) after weaning on day 20 of age. Caffeine ingestion had little effects on any of the day of vaginal opening, body growth, pattern of estrous cycles, mammary gland growth and reproduction ex...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(86)90653-3
更新日期：1986-07-28 00:00:00
abstract：:Plants are potentially important for novel therapeutic drug leads, but the slowness of conventional methods for investigation of plants limits enthusiasm in the pharmaceutical industry. To overcome some of the drawbacks, we have applied high throughput pharmacological screening (HTPS) to crude plant extracts. Using a ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2005.09.013
更新日期：2005-12-22 00:00:00
abstract：:Previous studies indicated that exogenous dopamine and its agonists directly regulated mitogen-induced immune cell proliferation. In this study, we further investigated role of endogenous dopamine in immune cell growth. Haloperidol, a general antagonist for dopamine receptors, could reduce the cell growth rate of T ce...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(98)00170-2
更新日期：1998-01-01 00:00:00
abstract：:Increased oxidative stress plays a role in the pathogenesis of beta-cell dysfunction and death. We studied isoforms of NADPH oxidase components in islets of Langerhans isolated from rat pancreas and tumoral rat beta-cell line RINm5F cells by RT-PCR and sequencing of its products. RT-PCR revealed that isolated islets c...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2006.08.031
更新日期：2006-12-14 00:00:00
abstract：:Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attribute...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/j.lfs.2019.117032
更新日期：2019-12-15 00:00:00
abstract：:Muscarinic receptors are expressed in smooth muscle throughout the body. In most instances, the muscarinic receptor population in smooth muscle is composed of mainly the M2 and M3 subtypes in an 80% to 20% mixture. The M3 subtype mediates phosphoinositide hydrolysis and calcium mobilization, whereas the M2 subtype med...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/s0024-3205(97)00433-5
更新日期：1997-01-01 00:00:00
abstract：AIMS:To explore the carcinostatic effects of platinum nanocolloid (Pt-nc) combined with gamma rays on human esophageal squamous cell carcinoma (ESCC). MAIN METHODS:ESCC-derived KYSE-70 cells were treated with various concentrations of Pt-nc and/or gamma irradiation, and subsequently cultured in phenol red free DMEM wi...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2015.01.028
更新日期：2015-04-15 00:00:00
abstract：:Cerebroventricular perfusate (CVP) from rats subjected to endotoxic shock was infused into the lateral ventricle of the naive rat. This procedure produced a hypotensive response in the recipient rat which could be reversed by the intravenous injection of the opioid antagonist naltrexone. The degree of endotoxemic hypo...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(92)90053-r
更新日期：1992-01-01 00:00:00
abstract：AIMS:Serotonergic neurons and amino acid neurons are involved in the central nervous control of lower urinary tract function. We investigated the role of the serotonergic system in the central regulation of micturition, as well as the relationship between serotonergic neurons and amino acid neurons in the lumbosacral c...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2009.08.013
更新日期：2009-10-07 00:00:00
abstract：:Intestinal mucosa, bone marrow hematopoietic cells and brain have limited capacity for the de novo synthesis of nucleosides (NSs) and nucleotides (NTs). Whereas the role of dietary NS and NT in the former two tissues is known, it is not known in the brain. Therefore we studied the effect of dietary NS and NT mixture o...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(96)00526-7
更新日期：1996-01-01 00:00:00
abstract：BACKGROUND:Most hepatocellular carcinoma cases are diagnosed at late stages of the disease, which makes it the second cause of cancer mortality worldwide. For advanced-stage patients, chemotherapeutic drugs are the best treatment option; however, their adverse effects and high cost are still major obstacles for effecti...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2020.118827
更新日期：2021-01-15 00:00:00
abstract：:Osteoarthritis (OA) is a complex joint disorder with a number of underlying physical, biochemical, biomechanical and genetic causes. Obesity is considered to be one of the major risk factors for the development and progression of OA. It actively contributes to the inflammatory status and to cartilage degradation in th...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/j.lfs.2015.05.025
更新日期：2015-11-01 00:00:00
abstract：:Using a two-lever drug discrimination procedure, six rats were trained to discriminate 0.5 mg/kg of racemic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) from saline. Once trained, the animals demonstrated a dose-related decrease in discriminative performance upon administration of lower doses of DOI (ED50 = 0.1...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(86)90461-3
更新日期：1986-09-01 00:00:00
abstract：BACKGROUND:Quercetin is a major flavonoid in various plants. It possesses the multiple pharmacological actions like vascular integrity and regulatory action of the blood-brain barrier. AIMS:The present study is focused on evaluating the role of solid lipid nanoparticle of quercetin in pentylenetetrazole (PTZ) induced ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2018.03.010
更新日期：2018-04-15 00:00:00
abstract：:Previous studies with N-terminal fragments of substance P (SP) have suggested the existence of two separate SP receptor populations. SP1 receptors are found in guinea pig ilea and rat colons. SP2 receptors are found in mouse spinal cords and rat salivary glands. We have now found that substitution of Gly9 in substance...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(85)90198-5
更新日期：1985-02-25 00:00:00
abstract：:Muscarinic agonists elicit contraction in the standard guinea pig ileum bioassay through activation of M3 muscarinic receptors that are also linked to phosphoinositide hydrolysis. Surprisingly, the most abundant muscarinic receptor in the ileum is the M2 which causes a specific inhibition of cyclic AMP accumulation el...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/0024-3205(94)00035-q
更新日期：1995-01-01 00:00:00
abstract：:The role of alpha 1-adrenoceptors in the mediation of autonomic functions, particularly in the control of the cardiovascular system, is widely known. It has been shown that alpha 1-adrenoceptors localized in human prostate mediate the contraction of prostatic smooth muscles which produces an increase in the intraureth...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/0024-3205(94)90141-4
更新日期：1994-01-01 00:00:00
abstract：:The influence of prior incubation on [3H]tryptamine binding was investigated in rat brain synaptic plasma membranes. A 55 min preincubation of the membranes at 37 degrees C induced an approx. 2.4-fold increase in the specific binding of [3H]ligand to the subsequently washed preparations and this phenomenon was quite t...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(86)90428-5
更新日期：1986-04-07 00:00:00
abstract：:We have used the antibiotic gradient-plate technique to generate antifungal producing Actinomadura strains that synthesize enhanced quantities of component 3A of a macrocyclic lactam antifungal compound Sch 38516. Seventy-nine colonies were selected from a mixture of rifampicin and spectinomycin gradient plates. The t...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(92)90336-n
更新日期：1992-01-01 00:00:00
abstract：:Positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to sympathomimetic amines were examined at bath temperatures of 38, 30 or 25 degrees C. The concentration-response curves to isoproterenol and orciprenaline were displaced to the left by cooling, indicating hypothermia-induced su...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(84)90074-2
更新日期：1984-09-03 00:00:00
abstract：:The hyperphagia and rapid body weight gain normally observed in young obese (ob/ob) mice were abolished by removal of their adrenal glands, whereas food intake and weight gain of lean mice were not significantly affected by adrenalectomy. Adrenalectomy lowered body energy density (kcal/g carcass) in obese mice more th...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(84)90056-0
更新日期：1984-04-09 00:00:00
abstract：AIMS:TsTX-I scorpion toxin, also known as γ-toxin, is a β-toxin which binds to site 4 of the sodium channel, shifting its activation potential. There are few studies about its pharmacological action in the central nervous system. The objective of this work was to determine the electroencephalographic, behavioral and hi...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2010.09.007
更新日期：2010-10-09 00:00:00
abstract：:Previous investigations showed that chronic metabolic acidosis (CMA) increased the paracellular permeability of ion and neutral hydrophilic molecules in the duodenum of rats and small intestinal-like cell lines. Since proteins of the claudin family have been known to regulate the paracellular transport in several epit...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2007.01.063
更新日期：2007-04-17 00:00:00
abstract：:Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF impr...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2016.02.028
更新日期：2016-03-01 00:00:00
abstract：:During the myocardial protection induced by ischemic preconditioning a reduction in myocardial metabolism occurs due to activation of the A1 adenosine receptors. This study investigates whether preconditioning changes both resting coronary flow and the magnitude of coronary reactive hyperemia and whether A1 adenosine ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(99)00034-x
更新日期：1999-01-01 00:00:00
abstract：AIM:The aim of the present study was to assess and compare the effect of 17β-estradiol and two different selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, as well as a selective estrogen receptor alpha agonist, propyl-pyrazole-triol (PPT) and a selective estrogen receptor beta agonist, diarylpro...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2011.03.010
更新日期：2011-05-09 00:00:00
abstract：:Trichosanthin (TCS) is a type 1 ribosome-inactivating protein (RIP) effective against HIV-1 and HSV-1 replication. The mechanism of its antiviral activity is not clear. Many believe that it is related to ribosome inactivation. Some RIPs and viral infection affect the phosphorylation of MAPK and Bcl-2 and these protein...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2006.03.047
更新日期：2006-08-22 00:00:00
