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About 48,278 results

A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry ...
https://doi.org/10.1073/pnas.2108728118
Proceedings of the National Academy of Sciences of the Un... Mahoney M, Damalanka VC et. al.

Oct 13th, 2021 - The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we ha...

Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models.
https://doi.org/10.1038/s41467-021-26084-3 10.1172/JCI78167 10.1038/s41583-018-0006-3 10.1038/13810 10.1016/0092-8674(92)90610-O 10.1016/j.molcel.2010.01.030 10.1126/science.abd5581 10.1038/85906 10.1038/85899 10.1038/nn.3434 10.1038/nature14319 10.1016/j.molcel.2019.10.032 10.1126/science.1153252 10.1038/nrm3525 10.1016/j.molcel.2019.09.017 10.1073/pnas.0507856102 10.1371/journal.pgen.1006129 10.1038/ng.841 10.1016/j.neuron.2018.09.026 10.1101/gad.182477.111 10.7554/eLife.45418 10.1016/j.neuron.2018.01.020 10.1093/emboj/cdg089 10.1074/jbc.M511556200 10.1101/gad.1703108 10.1038/nsmb.1545 10.1016/j.cell.2016.03.040 10.1016/j.cell.2017.06.022 10.1016/j.jmb.2018.05.014 10.1016/j.celrep.2014.02.005 10.1016/j.molcel.2007.12.028 10.1172/JCI90967 10.1016/j.cell.2017.10.024 10.1038/nrm3920 10.1074/jbc.M700855200 10.1038/nm.4406 10.1007/s10038-004-0145-4 10.1126/science.1138659 10.1371/journal.pgen.1005226 10.1371/journal.pone.0073323 10.1038/nature10110 10.1038/nn.4536 10.1016/j.neuron.2019.03.032 10.1038/nrm.2017.7 10.1126/science.aaf4382 10.1007/s11427-020-1702-x 10.1038/s41422-020-0288-7 10.1038/s41421-020-0172-0 10.1038/s41586-020-2574-4 10.1146/annurev-biochem-060614-034242 10.1038/cr.2013.110 10.1038/ncomms15134 10.1016/j.cell.2017.06.037 10.1093/bioinformatics/btu170 10.1093/nar/gky955 10.1038/nmeth.3317 10.1093/bioinformatics/btu638 10.1073/pnas.1419161111 10.1016/j.ajhg.2020.07.005 10.1016/j.ymeth.2019.10.003 10.1016/j.ymeth.2019.11.008 10.1093/bioinformatics/btx330 10.1093/bioinformatics/bts635 10.1101/gr.209601.116 10.1002/0471250953.bi1112s47 10.1186/s13059-017-1364-2 10.1016/j.cell.2012.12.023 10.1038/nmeth.1923 10.1093/bioinformatics/btp352 10.1186/gb-2008-9-9-r137 10.1093/bioinformatics/btv145
Nature Communications; Jiang Y, Fu X et. al.

Oct 3rd, 2021 - Rett syndrome (RTT) is a severe neurological disorder and a leading cause of intellectual disability in young females. RTT is mainly caused by mutations found in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Despite extensive studies, the molecular mechanism underlying RTT pathogenesis is still poorly understood. Here, we report MeCP2 as a key subunit of a higher-order multiu...

Local topology and bifurcation hot-spots in proteins with SARS-CoV-2 spike protein as a...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483365
PloS One; Peng X, Niemi AJ

Oct 1st, 2021 - Novel topological methods are introduced to protein research. The aim is to identify hot-spot sites where a bifurcation can alter the local topology of the protein backbone. Since the shape of a protein is intimately related to its biological function, a substitution that causes a bifurcation should have an enhanced capacity to change the protein's function. The methodology applies to any prote...

Network Pharmacology Reveals That Resveratrol Can Alleviate COVID-19-Related Hyperinfla...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463930
Disease Markers; Xiao Z, Ye Q et. al.

Sep 29th, 2021 - Hyperinflammation is related to the development of COVID-19. Resveratrol is considered an anti-inflammatory and antiviral agent. Herein, we used a network pharmacological approach and bioinformatic gene analysis to explore the pharmacological mechanism of Resveratrol in COVID-19 therapy. Potential targets of Resveratrol were obtained from public databases. SARS-CoV-2 differentially expressed ge...

Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordic...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474883
Journal of Ovarian Research; Singh SK, Singh S et. al.

Sep 29th, 2021 - Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica ch...

Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475993
PloS One; Schrörs B, Riesgo-Ferreiro P et. al.

Sep 28th, 2021 - Due to the widespread of the COVID-19 pandemic, the SARS-CoV-2 genome is evolving in diverse human populations. Several studies already reported different strains and an increase in the mutation rate. Particularly, mutations in SARS-CoV-2 spike-glycoprotein are of great interest as it mediates infection in human and recently approved mRNA vaccines are designed to induce immune responses against...

IFITM1, CD10, SMA, and h-caldesmon as a helpful combination in differential diagnosis b...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461929
BMC Cancer; Zhao W, Cui M et. al.

Sep 25th, 2021 - The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldes...

Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell...
https://doi.org/10.1073/pnas.2106947118
Proceedings of the National Academy of Sciences of the Un... Aggarwal RK, Luchtel RA et. al.

Sep 24th, 2021 - Reduced succinate dehydrogenase (SDH) activity resulting in adverse succinate accumulation was previously considered relevant only in 0.05 to 0.5% of kidney cancers associated with germline SDH mutations. Here, we sought to examine a broader role for SDH loss in kidney cancer pathogenesis/progression. We report that underexpression of SDH subunits resulting in accumulation of oncogenic succinat...

A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian gold...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458290
Nature Communications; Huo J, Mikolajek H et. al.

Sep 24th, 2021 - SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered...

Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody co...
https://doi.org/10.1038/s41564-021-00972-2 10.1016/j.cell.2020.02.052 10.1038/s41564-020-0688-y 10.1128/mSphere.00160-20 10.1073/pnas.1708727114 10.1038/s41598-020-73491-5 10.1038/s41591-020-0897-1 10.1016/j.cell.2020.09.037 10.1126/science.abc5902 10.1016/j.cell.2020.05.025 10.1126/science.abd0827 10.1038/s41586-020-2380-z 10.1038/s41586-020-2571-7 10.1038/s41586-020-2456-9 10.1126/science.abc7520 10.1038/s41586-020-2381-y 10.4049/jimmunol.171.9.4680 10.1038/s41586-020-2548-6 10.1038/s41586-020-2772-0 10.1126/science.abb2507 10.1038/s41594-020-0468-7 10.1038/s41591-020-0998-x 10.1038/s41467-021-24435-8 10.1126/science.abe3354 10.1016/j.cell.2020.06.044 10.1093/nar/gki385 10.1016/j.cell.2021.02.032 10.1038/s41586-019-0934-8 10.1016/j.chom.2020.11.007 10.1016/j.cell.2020.08.012 10.1016/j.chom.2020.06.021 10.1099/jgv.0.001481 10.1073/pnas.2025601118 10.1126/science.abe2402 10.1016/j.cell.2020.07.012 10.15585/mmwr.mm7003e2 10.2807/1560-7917.ES.2020.26.1.2002106 10.1038/s41586-021-03402-9 10.1128/JVI.00119-21 10.1038/s41586-021-03693-y 10.1016/j.cell.2021.04.025 10.1038/s41591-021-01294-w 10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.02.003 10.1038/s41591-021-01285-x 10.1073/pnas.2103154118 10.1038/s41586-021-03471-w 10.1016/j.chom.2021.04.007 10.1038/s41586-021-03398-2 10.1038/s41586-021-03324-6 10.1038/s41586-020-2012-7 10.4049/jimmunol.180.5.3279 10.1126/science.1207532 10.1016/j.cell.2015.05.007 10.1073/pnas.0308527100 10.1126/science.aab1253 10.1016/j.cell.2016.06.043 10.1038/nature13764 10.1038/nsmb.1566 10.4049/jimmunol.1402835 10.1172/jci.insight.92872 10.1073/pnas.1114927109 10.1126/science.abd2321 10.1016/j.chom.2020.09.002 10.1084/jem.20151960 10.1016/j.cell.2021.01.037 10.1107/S0907444909047337 10.1107/S0907444910045749 10.1107/S0021889807021206 10.1107/S0907444909052925 10.1107/S0907444904019158 10.1126/science.abf9302 10.1073/pnas.1804015115 10.1126/science.abd0826 10.1038/s41586-020-2895-3 10.1016/j.chom.2020.04.004 10.1038/msb.2011.75 10.1186/1471-2105-5-113 10.1101/gr.849004
Nature Microbiology; Dong J, Zost SJ et. al.

Sep 23rd, 2021 - Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies-AZD8895 and AZD1061-which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor-binding domain (RBD) of SARS-CoV-2 to define the gene...

Ttc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polyc...
https://doi.org/10.1073/pnas.2106770118
Proceedings of the National Academy of Sciences of the Un... Getwan M, Hoppmann A et. al.

Sep 23rd, 2021 - Skeletal ciliopathies (e.g., Jeune syndrome, short rib polydactyly syndrome, and Sensenbrenner syndrome) are frequently associated with nephronophthisis-like cystic kidney disease and other organ manifestations. Despite recent progress in genetic mapping of causative loci, a common molecular mechanism of cartilage defects and cystic kidneys has remained elusive. Targeting two ciliary chondrodys...

Isonicotinylation is a histone mark induced by the anti-tuberculosis first-line drug is...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452692
Nature Communications; Jiang Y, Li Y et. al.

Sep 22nd, 2021 - Isoniazid (INH) is a first-line anti-tuberculosis drug used for nearly 70 years. However, the mechanism underlying the side effects of INH has remained elusive. Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (Kinic), also called 4-picolinylation, in cells and mice. INH promotes the biosynthesis of isonicotinyl-Co...

A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nan...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448731
Nature Communications; Chen X, Gentili M et. al.

Sep 19th, 2021 - Antibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of 1011 randomized sequences. We apply CeVICA to engineer nanobodies against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and identify >800 binder f...

Structure of SARS-CoV-2 spike protein.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423807
Current Opinion in Virology; Zhang J, Xiao T et. al.

Sep 18th, 2021 - The COVID-19 (coronavirus disease 2019) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to loss of human life in millions and devastating socio-economic consequences worldwide. The disease has created urgent needs for intervention strategies to control the crisis and meeting these needs requires a deep understanding of the structure-function relationshi...

Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic t...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440555
Nature Communications; Alvarez-Benayas J, Trasanidis N et. al.

Sep 16th, 2021 - Multiple myeloma is a genetically heterogeneous cancer of the bone marrow plasma cells (PC). Distinct myeloma transcriptome profiles are primarily driven by myeloma initiating events (MIE) and converge into a mutually exclusive overexpression of the CCND1 and CCND2 oncogenes. Here, with reference to their normal counterparts, we find that myeloma PC enhanced chromatin accessibility combined wit...

Development of in-house, indirect ELISAs for the detection of SARS-CoV-2 spike protein-...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439474
PloS One; de la Guardia C, Rangel G et. al.

Sep 15th, 2021 - COVID-19 is the name of the acute respiratory disease caused by the new coronavirus SARS-CoV-2, a close relative of those that caused the severe outbreaks of SARS and MERS several years ago. Since first appearance on December of 2019, the COVID-19 pandemic has cause extremely high levels of mortality, morbidity, global economic breakdown, and the consequent human suffering. The main diagnostic ...

The SARS-CoV-2 spike protein is vulnerable to moderate electric fields.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437970
Nature Communications; Arbeitman CR, Rojas P et. al.

Sep 15th, 2021 - Most of the ongoing projects aimed at the development of specific therapies and vaccines against COVID-19 use the SARS-CoV-2 spike (S) protein as the main target. The binding of the spike protein with the ACE2 receptor (ACE2) of the host cell constitutes the first and key step for virus entry. During this process, the receptor binding domain (RBD) of the S protein plays an essential role, since...

Theaflavin-3'-O-gallate a Black-tea Constituent Blocked SARS CoV-2 RNA dependant RNA Po...
https://doi.org/10.1055/a-1467-5828
Drug Research; Banerjee A, Kanwar M et. al.

Sep 14th, 2021 - Replication of SARS-CoV-2 depends on viral RNA-dependent RNA-polymerase (RdRp). Remdesivir, the broad-spectrum RdRp inhibitor acts as nucleoside-analogues (NAs). Remdesivir has initially been repurposed as a promising drug against SARS-CoV-2 infection with some health hazards like liver damage, allergic reaction, low blood-pressure, and breathing-shortness, throat-swelling. In comparison, theaf...

Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 prop...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431879
International Journal of Biological Macromolecules; Ali N, Prasad K et. al.

Sep 14th, 2021 - SARS-CoV-2 nucleocapsid (N) protein undergoes RNA-induced phase separation (LLPS) and sequesters the host key stress granule (SG) proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and 2 (G3BP1 and G3BP2) to inhibit SG formation. This will allow viral packaging and propagation in host cells. Based on a genomic-guided meta-analysis, here we identify upstream regulatory elements...

Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426591
Molecular Medicine (Cambridge, Mass.); Duarte RRR, Copertino DC et. al.

Sep 11th, 2021 - Vaccination programs have been launched worldwide to halt the spread of COVID-19. However, the identification of existing, safe compounds with combined treatment and prophylactic properties would be beneficial to individuals who are waiting to be vaccinated, particularly in less economically developed countries, where vaccine availability may be initially limited. We used a data-driven approach...