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Fatima Amanat Shirin Strohmeier Philip S. Meade Nicholas Dambrauskas Barbara Mühlemann Derek J. Smith Vladimir Vigdorovich D. Noah Sather Lynda Coughlan Florian Krammer 《PLoS biology》2021,19(12)
Vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against Coronavirus Disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild-type SARS-CoV-2 and from variants B.1.1.7, B.1.351, and P.1 for their immunogenicity and protective effect in vivo against challenge with wild-type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7-vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild-type SARS-CoV-2 in a mouse model.This study explores the immune response induced by wild type and variant SARS-CoV-2 spike proteins, and the protection that these immune responses provide against challenge with wild type virus in the mouse model. 相似文献
173.
Sunniya Iftikhar Sardraz Khan Aishah Bilal Safia Manzoor Muhammad Abdullah Abdel-Hamid Emwas Salim Sioud Xin Gao Ghayoor Abbas Chotana Amir Faisal Rahman Shah Zaib Saleem 《Bioorganic & medicinal chemistry letters》2017,27(17):4101-4106
Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death in response to various cellular stresses thereby preventing cancer development. Activation and stabilization of p53 through small organic molecules is, therefore, an attractive approach for the treatment of cancers retaining wild-type p53. In this context, a series of nineteen chalcones with various substitution patterns of functional groups including chloro, fluoro, methoxy, nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt condensation. The compounds were characterized using NMR, HRMS, IR and melting points. Evaluation of synthesized compounds against human colorectal (HCT116) and breast (CAL-51) cancer cell lines revealed potent antiproliferative activities. Nine compounds displayed GI50 values in the low micromolar to submicromolar range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (SSE14108) showed GI50 of 0.473 ± 0.043 µM against HCT116 cells. Further analysis of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused rapid (4 and 8-h post-treatment) accumulation of p53 in HCT116 cells similar to its induction by positive control, Nutlin-3. Such activities were absent in 3-(4-methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of conjugated ketone for antiproliferative and p53 stabilizing activity of the chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX) and the results showed that the p53 stabilization was regulated at post-translational level through blockage of its degradation. These chalcones can, therefore, act as fragment leads for further structure optimization to obtain more potent p53 stabilizing agents with enhanced anti-proliferative activities. 相似文献
174.
Mohammad Fawad Ansari Faisal Hayat Afreen Inam Fatima Kathrada Robyn L. van Zyl Maureen Coetzee Kamal Ahmad Dongyun Shin Amir Azam 《Bioorganic & medicinal chemistry letters》2017,27(3):460-465
In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5–14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC50 values (0.14–1.26 μM) lower than the standard drug metronidazole (IC50 1.80 μM). All nine compounds exhibited antimalarial activity (IC50 range: 1.42–19.62 μM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC50 range: 14.67–81.24 μM) than quinine (IC50: 275.6 ± 16.46 μM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae. 相似文献
175.
Amino acid transporter mutants of Arabidopsis provides evidence that a non‐mycorrhizal plant acquires organic nitrogen from agricultural soil 下载免费PDF全文
Ulrika Ganeteg Iftikhar Ahmad Sandra Jämtgård Camila Aguetoni‐Cambui Erich Inselsbacher Henrik Svennerstam Susanne Schmidt Torgny Näsholm 《Plant, cell & environment》2017,40(3):413-423
Although organic nitrogen (N) compounds are ubiquitous in soil solutions, their potential role in plant N nutrition has been questioned. We performed a range of experiments on Arabidopsis thaliana genetically modified to enhance or reduce root uptake of amino acids. Plants lacking expression of the Lysine Histidine Transporter 1 (LHT1) displayed significantly lower contents of 13C and 15N label and of U‐13C5,15N2 L‐glutamine, as determined by liquid chromatography–mass spectrometry when growing in pots and supplied with dually labelled L‐glutamine compared to wild type plants and LHT1‐overexpressing plants. Slopes of regressions between accumulation of 13C‐labelled carbon and 15N‐labelled N were higher for LHT1‐overexpressing plants than wild type plants, while plants lacking expression of LHT1 did not display a significant regression between the two isotopes. Uptake of labelled organic N from soil tallied with that of labelled ammonium for wild type plants and LHT1‐overexpressing plants but was significantly lower for plants lacking expression of LHT1. When grown on agricultural soil plants lacking expression of LHT1 had the lowest, and plants overexpressing LHT1 the highest C/N ratios and natural δ15N abundance suggesting their dependence on different N pools. Our data show that LHT1 expression is crucial for plant uptake of organic N from soil. 相似文献
176.
A Molecular Docking and Dynamics Approach to Screen Potent Inhibitors Against Fosfomycin Resistant Enzyme in Clinical Klebsiella pneumoniae 下载免费PDF全文
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Georgia Pacheco Rachel Fatima Gagliardi Leonardo Alves Carneiro José Francisco Montenegro Valls Elisabeth Mansur 《In vitro cellular & developmental biology. Plant》2008,44(1):14-17
Seed explants of A. stenosperma were cultured on MS medium supplemented with 6-benzylaminopurine with the aim of rescuing nonviable accessions stored in
seed bank conditions. The regeneration potential of leaf explants from in vitro plants derived from embryonic axes was studied by using whole leaflets and leaflet segments. Explants were cultured on Murashige
and Skoog (MS) medium supplemented with different concentrations of 6-benzylaminopurine and naphthalene acetic acid. Indirect
organogenesis was observed in response to 6-benzylaminopurine, either alone or in association with naphthalene acetic acid,
in both explant types. Media supplemented with naphthalene acetic acid as the sole growth regulator induced rhizogenesis in
whole leaflets and leaflet segments, with subsequent shoot production directly from the roots. 相似文献
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