Abstract:
:The COVID-19 pandemic caused by the SARS-CoV-2 requires a fast development of antiviral drugs. SARS-CoV-2 viral main protease (Mpro, also called 3C-like protease, 3CLpro) is a potential target for drug design. Crystal and co-crystal structures of the SARS-CoV-2 Mpro have been solved, enabling the rational design of inhibitory compounds. In this study we analyzed the available SARS-CoV-2 and the highly similar SARS-CoV-1 crystal structures. We identified within the active site of the Mpro, in addition to the inhibitory ligands' interaction with the catalytic C145, two key H-bond interactions with the conserved H163 and E166 residues. Both H-bond interactions are present in almost all co-crystals and are likely to occur also during the viral polypeptide cleavage process as suggested from docking of the Mpro cleavage recognition sequence. We screened in silico a library of 6900 FDA-approved drugs (ChEMBL) and filtered using these key interactions and selected 29 non-covalent compounds predicted to bind to the protease. Additional screen, using DOCKovalent was carried out on DrugBank library (11,414 experimental and approved drugs) and resulted in 6 covalent compounds. The selected compounds from both screens were tested in vitro by a protease activity inhibition assay. Two compounds showed activity at the 50 µM concentration range. Our analysis and findings can facilitate and focus the development of highly potent inhibitors against SARS-CoV-2 infection.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Shitrit A,Zaidman D,Kalid O,Bloch I,Doron D,Yarnizky T,Buch I,Segev I,Ben-Zeev E,Segev E,Kobiler Odoi
10.1038/s41598-020-77794-5subject
Has Abstractpub_date
2020-11-30 00:00:00pages
20808issue
1issn
2045-2322pii
10.1038/s41598-020-77794-5journal_volume
10pub_type
杂志文章abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-019-54834-3
更新日期:2019-12-04 00:00:00
abstract::This corrects the article DOI: 10.1038/srep34617. ...
journal_title:Scientific reports
pub_type: 杂志文章,已发布勘误
doi:10.1038/srep42267
更新日期:2017-09-27 00:00:00
abstract::Bed bugs are pests of public health importance due to their relentless biting habits that can lead to allergies, secondary infections and mental health issues. When not feeding on human blood bed bugs aggregate in refuges close to human hosts. This aggregation behaviour could be exploited to lure bed bugs into traps f...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-61368-6
更新日期:2020-03-12 00:00:00
abstract::A major challenge in current exome sequencing in autosomal recessive (AR) families is the lack of an effective method to prioritize single-nucleotide variants (SNVs). AR families are generally too small for linkage analysis, and length of homozygous regions is unreliable for identification of causative variants. Vario...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12028
更新日期:2015-07-06 00:00:00
abstract::During development, cell division often generates two daughters with different developmental fates. Distinct daughter identities can result from the physical polarity and size asymmetry itself, as well as the subsequent activation of distinct fate programmes in each daughter. Asymmetric divisions are a feature of the ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-01675-7
更新日期:2017-06-14 00:00:00
abstract::Local drug delivery systems (DDS) have become a favourable approach for the treatment of numerous diseases. Biomedical imaging techniques such as ultrahigh field magnetic resonance imaging (UHF-MRI) offer unique insight into DDS biodegradation in vivo. We describe the establishment of a 7 Tesla MRI routine for longitu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-15954-w
更新日期:2017-11-17 00:00:00
abstract::The formation of proper sensory afferent connections during development is essential for brain function. Activity-based competition is believed to drive ocular dominance columns (ODC) in mammals and in experimentally-generated three-eyed frogs. ODC formation is thus a compromise of activity differences between two eye...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08338
更新日期:2015-02-09 00:00:00
abstract::There is a demand for ultra low-loss metal films with high-quality single crystals and perfect surface for nanophotonics and quantum information processing. Many researches are devoted to alternative materials, but silver is by far theoretically the most preferred low-loss material at optical and near-IR frequencies. ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-48508-3
更新日期:2019-08-22 00:00:00
abstract::Atomic Fermi gases have been an ideal platform for simulating conventional and engineering exotic physical systems owing to their multiple tunable control parameters. Here we investigate the effects of mixed dimensionality on the superfluid and pairing phenomena of a two-component ultracold atomic Fermi gas with a sho...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-13321-3
更新日期:2017-10-11 00:00:00
abstract::Methicillin-resistant Staphylococcus aureus (MRSA), are the most frequent cause of sepsis, which urgently demanding new drugs for treating infection. Two homologous insect CSαβ peptides-DLP2 and DLP4 from Hermetia illucens were firstly expressed in Pichia pastoris, with the yields of 873.5 and 801.3 mg/l, respectively...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10839-4
更新日期:2017-09-21 00:00:00
abstract::Knowledge about a tool's dynamics can be acquired from the visual configuration of the tool and through physical interaction. Here, we examine how visual information affects the generalization of dynamic learning during tool use. Subjects rotated a virtual hammer-like object while we varied the object dynamics separat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39507-5
更新日期:2019-02-25 00:00:00
abstract::The GacS/GacA two-component system (also called GrrS/GrrA) is a global regulatory system which is highly conserved among gamma-proteobacteria. This system positively regulates non-coding small regulatory RNA csrB, which in turn binds to the RNA-binding protein CsrA. However, how GacS/GacA-Csr system regulates virulenc...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37195
更新日期:2016-11-15 00:00:00
abstract::Dysregulation of dopaminergic system induced by HIV-1 Tat protein-mediated direct inhibition of the dopamine transporter (DAT) has been implicated as a mediating factor of HIV-1 associated neurocognitive disorders. We have reported that single point mutations on human DAT (hDAT) at tyrosine88 (Y88F), lysine92 (K92M), ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39872-1
更新日期:2019-03-07 00:00:00
abstract::The effects of sea salt aerosols (SSA) on cloud microphysical processes, precipitation, and upper troposphere/lower stratosphere water vapour in tropical cyclones were studied with the Weather Research and Forecasting with Chemistry model. Two numerical experiments were conducted: a control experiment (CTL) and an exp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-51757-x
更新日期:2019-10-22 00:00:00
abstract::It is frequently assumed that in the limit of vanishing cooling rate, the glass transition phenomenon becomes a thermodynamic transition at a temperature TK. However, with any finite cooling rate, the system falls out of equilibrium at temperatures near Tg(>TK), implying that the very existence of the putative thermod...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12577
更新日期:2015-07-24 00:00:00
abstract::Plumbagin, an anti-cancer agent, is toxic to cells of multiple species. We investigated if plumbagin targets conserved biochemical processes. Plumbagin induced DNA damage and apoptosis in cells of diverse mutational background with comparable potency. A 3-5 fold increase in intracellular oxygen radicals occurred in re...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-19261-w
更新日期:2018-01-18 00:00:00
abstract::Living organisms employ various mechanisms to escape harm. At the cellular level, mobile cells employ movement to avoid harmful chemicals or repellents. The present study is the first to report that cells move away from the site of injury in response to local wounding. When a migrating Dictyostelium cell was locally w...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39678-1
更新日期:2019-03-12 00:00:00
abstract::The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbin...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03740-7
更新日期:2017-06-12 00:00:00
abstract::To obtain high performance CH3NH3PbI3 perovskite solar cells, it is highly important to realise a high open-circuit voltage. Calculation results based on a modified diode model have indicated that a low bare ratio ϕ of the perovskite film is the most important factor determining the open-circuit voltage, where ϕ is de...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep46141
更新日期:2017-04-12 00:00:00
abstract::The dramatic loss of honey bees is a major concern worldwide. Previous studies have indicated that neonicotinoid insecticides cause behavioural abnormalities and have proven that exposure to sublethal doses of imidacloprid during the larval stage decreases the olfactory learning ability of adults. The present study sh...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19298
更新日期:2016-01-13 00:00:00
abstract::For scanning x-ray microscopy, many attempts have been made to image the phase contrast based on a concept of the beam being deflected by a specimen, the so-called differential phase contrast imaging (DPC). Despite the successful demonstration in a number of representative cases at moderate spatial resolutions, these ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01307
更新日期:2013-01-01 00:00:00
abstract::Principal research on energy from thermonuclear fusion uses Deuterium-Tritium plasmas magnetically trapped in toroidal devices. As major scientific problem for an economic (i.e., really feasible) reactor, we must understand how to lead strongly heated plasmas to sustain a high fusion gain while large fraction of curre...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-27996-9
更新日期:2018-07-09 00:00:00
abstract::No study to date has prospectively evaluated the association between pre-diagnostic cruciferous vegetables intake and lung cancer survival among women. This analysis included 547 incident lung cancer cases identified from the Shanghai Women's Health Study (SWHS) during the follow-up period of 1997-2011. Dietary intake...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10306
更新日期:2015-05-19 00:00:00
abstract::A series of three remarkable complexes [PMo12O40]@[Cu6O(TZI)3(H2O)9]4·OH·31H2O (H3TZI = 5-tetrazolylisophthalic acid; denoted as HLJU-1, HLJU = Heilongjiang University), [SiMo12O40]@[Cu6O(TZI)3(H2O)9]4·32H2O (denoted as HLJU-2), and [PW12O40]@[Cu6O(TZI)3(H2O)6]4·OH·31H2O (denoted as HLJU-3) have been isolated by using...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25595
更新日期:2016-05-09 00:00:00
abstract::Insulin resistance is a major risk factor for metabolic diseases such as Type 2 diabetes. Although the underlying mechanisms of insulin resistance remain elusive, oxidative stress is a unifying driver by which numerous extrinsic signals and cellular stresses trigger insulin resistance. Consequently, we sought to under...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-20104-x
更新日期:2018-01-29 00:00:00
abstract::Breast cancer is the most frequently diagnosed malignancy among women, and triple-negative breast cancer (TNBC) is a highly aggressive subtype. Increasing evidence has shown that lncRNAs are involved in tumor growth, cell-cycle, and apoptosis through interactions with miRNAs or mRNAs. However, there is still limited d...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-51626-7
更新日期:2019-10-22 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-64447-w
更新日期:2020-05-05 00:00:00
abstract::In the present study rice straw (R, control) was mixed with Cowdung (C), Azolla (A) and cellulolytic fungus Aspergillus terreus (F) in different combinations viz. RC, RA, RF, RCF, RCA, RFA and RCFA and subjected to aerobic composting (Acom) and vermicomposting (Vcom - with Eisenia fetida). It was found that addition o...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-37880-1
更新日期:2019-02-04 00:00:00
abstract::Regret results from comparing non-optimal outcomes containing both gain and loss parts to better alternatives during decision-making. The present fMRI study aimed to explore whether levels of regret could change when gain or loss part of a non-optimal outcome was focused during a sequential risk taking task, i.e. the ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41374
更新日期:2017-02-01 00:00:00
abstract::Medication-related osteonecrosis of the jaw (MRONJ) represents a complication of bisphosphonate treatment that responds poorly to standard treatment. In a retrospective cohort study we investigated a possible role of Actinomyces spp. in the pathogenesis of MRONJ. Deep biopsies of necrotic bone were collected during su...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep31604
更新日期:2016-08-17 00:00:00