JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2024
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IF 5.6
Cong Wu,Qi Jiang,Hui Zhong,Xudong Zhou,Leping Liu,Tong Pan,Chao Liu,Wei Wang,Wenbing Sheng
An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 μM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.
研究领域:
药物化学
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病毒学
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生物信息学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Chendong Yang,Entao Li,Xiaoping Guo,Wenyu Xie,Yuanzhan Wang,Xuefei Huang,Sandra Chiu,Xuanjun Wu
Over the past 3 years, SARS-CoV-2 Omicron has been circulating globally with the emergence of multiple subvariants, including BA.5, BA.5.2, XBB, XBB.1, EG.5.1, HK.3, BA.2.86, JN.1, and KP.2. To combat these Omicron subvariants, several vaccines based on receptor-binding domain (RBD) dimers have been developed; however, RBD dimer vaccines require frequent updates to cope with the emergence of new variants. In contrast, the development of a safe, effective, and broad-spectrum vaccine against multiple Omicron subvariants, including the latest JN.1 and KP.2, would be a one-size-fits-all solution. Here, we designed BA.4/5 RBD-PC7A conjugate micelles by displaying the BA.4/5 RBD in PC7A micelles. Remarkably, the micelles elicited potent neutralizing antibodies (NAbs) in rabbits, effectively neutralizing BA.5.2, XBB.1.18, and HK.3 infections. Moreover, the micelles alone were able to induce NAbs in mice against the BA.5 variant. When a cytosine-phosphate-guanine (CpG) adjuvant was added and electrostatically adsorbed to the micelles, there was a significant increase in the antibody titers of IgG1, IgG2b, and IgG2c. This enhancement facilitated the broad neutralization of various strains, including BA.5.2, XBB.1.18, HK.3, JN.1, and KP.2. Furthermore, the micelles adsorbed with CpG protected golden hamsters from infection with the BA.5.2 strain. This study presents a potent and broadly neutralizing nanovaccine that includes the BA.4/5 RBD antigen and a CpG adjuvant. It demonstrates efficacy against multiple Omicron subvariants, including BA.5, BA.5.2, XBB.1.18, HK.3, JN.1, and KP.2, highlighting its potential for clinical translation.
研究领域:
免疫学
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病毒学
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疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2025
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IF 6
Jiahai Wang,Jianji Zhu,Yunhui Li,Cenlin Gui,Baian Zhu,Zhuobin Zhu,Daqi Chen
Enhancing the signal-to-noise ratio (SNR) has long been a focus of research in the development of nanopore sensors. Herein, a 3D DNA origami cube with adjustable rigidity that exhibits exceptional selectivity and an ultra-high SNR exceeding 100 is designed and optimized. The assembly of this 3D DNA origami cube relies on a single scaffold strand derived from target DNA/RNA, as well as multiple staple strands. This construction process ensures that the cube only forms in the presence of the target DNA/RNA, thereby providing a highly sensitive and specific detection strategy. Without any intermediate steps, DNA amplicons amplified from a plasmid containing the S gene of the Omicron variant of SARS-CoV-2 were successfully transformed into 3D DNA origami cubes in the presence of staple strands in a one-pot reaction process. Nanopore counting of 3D DNA origami cubes, instead of the direct detection of the target gene, significantly ameliorates the interference effect from non-target subjects possessing a similar size and charge. This approach features an ultra-low detection limit of 50 aM, with a broad detection range from 50 aM to 50 pM, even in commercial buffers that contain large amounts of enzymes, stable proteins, and other non-target DNA sequences. Moreover, the DNA origami cube has a thermal stability of up to 70°C, which allows it to be used in a wide range of scenarios, including harsh conditions. We aim to extend this approach to detect many other targets and to integrate it into broader diagnostic toolkits. Nevertheless, given space constraints, not all possible applications could be thoroughly explored within this study.
研究领域:
生物物理学
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纳米技术
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分子诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）