Algal Research-Biomass Biofuels and Bioproducts
·
2025
·
IF 4.5
Qiao-Hui Zeng,Zhi-En Yao,Xian-Min Zhou,Ping Qi,Xin-An Zeng
Inhibition of the biological activity of SARS-CoV-2 main protease (Mpro) effectively prevents viral replication, thereby presenting a promising therapeutic target for Corona Virus Disease 2019 (COVID-19) intervention. This study aims to screen the Mpro inhibitory peptides from the natural nutritional supplement Spirulina platensis ( S. platensis ). Firstly, Mpro was successfully prepared by heterologous expression in E. coli and Mpro's activity was detected. Meanwhile, four distinct peptides derived from S. platensis were obtained through enzymatic hydrolysis of protein. Subsequently, highly active peptides were synthesized and their inhibition effects on Mpro were verified by in vitro experiment and computer simulations. Results showed that the extraction rate of the protein from S. platensis was 96.11 %, the activity of Mpro was 845.90 U mg −1 , the peptide MQGPNY could inhibit the activity of Mpro at the inhibition rate of 20.21 % ± 3.8 % at the concentration of 2 mmol L −1 . Furthermore, results from computer Simulation showed that the peptide MQGPNY forms four pairs of hydrogen bonds with Mpro, which are Gln189, Ser46, Thr26 and Glu166. In addition, there were ten free residues involved in hydrophobic contacts, including His164, His41, Thr24, Met49, Thr45, Thr25, Gly143, Asn142, Cys145 and Met165. The foundings could provide theoretical support for the use of protein and its hydrolysates from S. platensis in functional food and supplement formulations in the post-epidemic era.
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Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 32
·6107-6117
·
IF 7.571
Siying Xie,Cheng Qin,Furong Zhao,Zhaoyang Shang,Pei Wang,Muhammad Sohail,Xing Zhang,Bingzhi Li
CRISPR-driven biosensing is developing rapidly, but current studies mostly adopt dye-labeled ssDNA as the signal reporter, which is costly and unstable. Herein, we developed a label-free and low-background reporter for CRISPR/Cas12a signaling by integrating DNA-templated copper nanoclusters (DNA–CuNCs) and exonuclease I (EXO I). The template of the DNA–CuNCs was rationally designed as a ds-/ss-DNA hybrid, ensuring that after a quick and nonpersistent cut of Cas12a, a majority of the template can be digested by EXO I. Based on this novel reporter, a biosensor termed CRISPR-CNS (cost-effective, nimble, and sensitive copper nanocluster sensor integrating CRISPR) was developed. Due to the high signal-to-background ratio of our proposed reporter, CRISPR-CNS shows excellent performances for nucleic acid detection, yielding a detection limit of 20 copies for SARS-CoV-2 RNA. Considering its facile synthesis, robust fluorescence, effective cost, and good sensitivity, this combination shall serve as a highly potential output for CRISPR-based point-of-care testing.
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MOLECULES
·
2023
·Vol. 28
·期 15
·5634
·
IF 4.6
Chen Sun,Bo Liu,Fengzhi Zhou,Qianqian Zheng,Chunmei Dai,Wei Wei,Guochao Liao,Yuqi Sun
SARS-CoV-2 is a highly contagious and pathogenic virus that first appeared in late December 2019 and caused a global pandemic in a short period. The virus is a single-stranded RNA virus belonging to the Coronaviridae family. Numerous treatments have been developed and tested in response to the pandemic, particularly antiviral drugs. Among them, GS441524 (GS441), a nucleoside antiviral drug, has demonstrated promising results in inhibiting SARS-CoV-2. Nevertheless, the limited oral bioavailability of GS441 restricts its application to patients with the virus. In this study, a novel prodrug of GS441 (NGP-1) with an isobutyl ester and cyclic carbonate structure was designed and synthesized. Its purity and the stability in different artificial digestive juices of NGP-1 was determined with HPLC-DAD methods. The pharmacokinetics of NGP-1 and GS441 were studied in rats via gavage administration. A new LC-MS/MS method was developed to quantitatively analyze GS441 in plasma samples. The results showed that the ka, Cmax, and MRT of converted GS441 from NGP-1 were 5.9, 3, and 2.5 times greater than those of GS441 alone. The Frelof NGP-1 was approximately four-fold that of GS441, with an AUC0–∞of 9716.3 h·ng mL−1. As a prodrug of GS441, NGP-1 increased its lipophilicity, absorption, and bioavailability, indicating that it holds promise in improving the clinical efficacy of anti-SARS-CoV-2 medications.Keywords:anti-SARS-CoV-2;prodrug of GS441524;purity;stability and pharmacokinetics;oral bioavailability;LC-MS/MS
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Biomolecules
·
2024
·Vol. 14
·期 12
·1568
·
IF 4.8
Rui Wang,Junping Xue,Guo Wei,Yimeng Zhang,Chuanliang Wang,Jinhua Li,Xuhui Geng,Abbas Ostovan,Lingxin Chen,Zhihua Song
The development of a novel strategy for the measurement of SARS-CoV-2 IgG antibodies is of vital significance forCOVID-19diagnosis and effect of vaccination evaluation. In this investigation, an SiO2@Au@CDs nanoparticle (NP)-based lateral flow immunoassay (LFIA) strip was fabricated and coupled with a miniaturized fluorimeter. The morphology features and particle sizes of the SiO2@Au@CDs NPs were characterized carefully, and the results indicated that the materials possess monodisperse, uniform, and spherical structures. Finally, this system was employed for SARS-CoV-2 IgG antibody test. In this work, the strategy for the SARS-CoV-2 IgG antibody test possesses several merits, such as speed (less than 15 min), high sensitivity (1.2 × 10−7mg/mL), broad linearity range (7.4 × 10−7~7.4 × 10−4mg/mL), accurate results, high selectivity, good stability, and low cost. Additionally, future trends in LFAs using quantum dot-based diagnostics are envisioned.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 5.9
Yan-Yun Liu,Zheng-Ao Li,Yu-Zheng Zhou,Sen-Lin Wang,Zong-Peng Chen,Si-Xu Liu,Peng Zhan,Ying-Jun Zhou,Zan-Xian Xia,Xu Deng
The global COVID-19 pandemic caused by SARS-CoV-2 has underscored the urgent need for the development of new broad-spectrum antivirals to combat its high mutation rate and the emerging variants. Host ER α-glucosidases I/II are promising host-targeted therapeutic targets for the development of broad-spectrum antivirals against viral strains that depend on ERQC for infectivity. Herein, we designed and synthesized a series of TCM theory-inspired DNJ-flavonoid conjugates as novel α-glucosidase inhibitors, which were screened against their in vitro antiviral activities in non-replicative SARS-CoV-2 pseudovirus (PsV) assay. Remarkably, DNJ-20 not only demonstrated remarkable inhibition activity against α-glucosidase and viral entry process, but also exerted potent and broad-spectrum anti-coronaviral activity against SARS-CoV-2 pseudovirus (PsV), several SARS-CoV-2 variants, as well as HCoV-229E and HCoV-OC43, with EC 50 values up to 1.49 μM, which is more potent than the benchmark α-glucosidase inhibitor UV-4 ( DNJ-3 ). Besides, it had no observable cytotoxicity in HeLa-ACE2, HEK-293T and Beas-2B cells. Therefore, TCM theory-inspired DNJ-flavonoid conjugates can be served as promising drug leads for pan-coronavirus therapeutic development to combat current and future coronavirus pandemics.
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MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Hongyu Zhu,Sen Yang,Jingyang Zhao,Liuyang Wang,Chenghao Gao,Yanan Sheng,Xuan Lin,Zhiguo Su,Kiichi Sato,Zhongyu Hu,Songping Zhang
All-trans retinoic acid (Ra) has been demonstrated to enhance the establishment of systemic and intestinal immunity for codelivered antigens; however, the extremely poor water solubility of Ra significantly limits its application in vaccines. Herein, leveraging the advantages of ionic liquids in modifying the physicochemical properties of small-molecule drugs, we synthesized a novel ionic liquid composed of choline and retinoic acid ([Cho][Ra]). Compared to Ra, [Cho][Ra] exhibited an 18165-fold increase in solubility at pH 7.4 and an acid-responsive Ra release behavior. The [Cho][Ra] was then formulated with the SARS-CoV-2 RBD antigen, and its adjuvant effects were comprehensively evaluated. The in vitro cellular studies indicated that at 50 μg Ra equivalent dose, the [Cho][Ra]@RBD showed significantly higher than RBD along in activation of BMDC and the expression of gut homing molecules, including C–C motif chemokine receptor 9 (CCR9, 10.55 folds), α4β7 integrin (13.29 folds), and lymph node migration molecule CCR7 (82.68 folds). Animal experiments showed that compared to RBD alone, [Cho][Ra]@RBD promoted the establishment of mucosal immunity in the intestines in mice at the early stage following subcutaneous immunization and elicited higher serum antibody levels. Furthermore, compared to RBD and Alum@RBD, [Cho][Ra]@RBD enhanced the formation of CD4+ TCM and CD8+ TCM cells, indicating stronger cellular immune responses. In summary, [Cho][Ra] showed potential adjuvant effects in enhancing the humoral and cellular immune responses, as well as in the establishment of intestinal mucosal immunity for RBD antigen without the need for delivery system, thereby offering promising prospects for applying Ra in vaccines.
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ACS Nano
·
2025
·
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.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lei huang,Siyuan Tang,Jiachen Guo,Yixing Tu,Sian Li,Xianchao Dai,Taihua Yang,Dong Zhao,Chao Wang
The development of tumor-retained and minimally invasive mRNA and photothermal therapies for superficial malignant tumors, such as breast cancer, remains a significant challenge. In this study, we present a novel tumor-retained lipid nanoparticle-microneedle (LNP-MN) patch for localized co-delivery of mRNA and the photothermal agent indocyanine green (ICG). By optimizing LNP formulations, ICG loading methodology, mRNA-to-ICG ratio, and MN matrix composition, we achieved a balanced platform ensuring high mRNA transfection efficiency and robust ICG photothermal performance. This LNP-MN platform enabled efficient intratumoral deposition, demonstrating a 15.6-fold increase in tumor accumulation compared to intravenous administration. For the first time, SARS-CoV-2 spike mRNA was combined with ICG-mediated photothermal therapy (PTT) within a single system for superficial tumor treatment. In a 4 T1 breast cancer model, this combinatorial strategy achieved significant tumor growth inhibition (75.1 %), enhanced CD8+ T-cell infiltration, and minimized systemic toxicity, outperforming monotherapies. This study pioneers the integration of PTT and mRNA-based tumor-labeling immunotherapy in a minimally invasive MN platform, offering a promising strategy for enhanced superficial cancer therapy.
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Signal Transduction and Targeted Therapy
·
2022
·Vol. 7
·期 1
·1-10
·
IF 38.104
Wu Jiajing,Nie Jianhui,Zhang Li,Song Hao,An Yimeng,Liang Ziteng,Yang Jing,Ding Ruxia,Liu Shuo,Li Qianqian,Li Tao,Cui Zhimin,Zhang Mengyi,He Peng,Wang Youchun,Qu Xiaowang,Hu Zhongyu,Wang Qihui,Huang Weijin
Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.
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ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 48
·2209743
·
IF 19.924
Yi-Xuan Li,Jing Li,Dunru Zhu,Ju-Zheng Wang,Guo-Fang Shu,Junji Li,Sheng-Li Zhang,Xue-Ji Zhang,Serge Cosnier,Hai-Bo Zeng,Dan Shan
High electrocatalytic activity with tunable luminescence is crucial for the development of electrochemiluminescence (ECL) luminophores. In this study, a porphyrin-based heterobimetallic 2D metal organic framework (MOF), [(ZnTCPP)Co 2 (MeIm)] (1), is successfully self-assembled from the zinc(II) tetrakis(4-carboxyphenyl)porphine (ZnTCPP) linker and cobalt(II) ions in the presence of 2-methylimidazole (MeIm) by a facile one-pot reaction in methanol at room temperature. On the basis of the experimental results and the theoretical calculations, the MOF 1 contains paddle–wheel [Co 2 (-CO 2 ) 4 ] secondary building units (SBUs) axially coordinated by a MeIm ligand, which is very beneficial to the electron transfer between the Co(II) ions and oxygen. Combining the photosensitizers ZnTCPP and the electroactive [Co 2 (-CO 2 ) 4 ] SBUs, the 2D MOF 1 possesses an excellent ECL performance, and can be used as a novel ECL probe for rapid nonamplified detection of the RdRp gene of SARS-CoV-2 with an extremely low limit of detection (≈30 aM).
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TALANTA
·
2021
·
IF 6.057
Kai Zhang,Zhenqiang Fan,Yue Huang,Yuedi Ding,Minhao Xie
Early diagnosis and timely management of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are the keys to preventing the spread of the epidemic and controlling new infection clues. Therefore, strengthening the surveillance of the epidemic and timely screening and confirming SARS-CoV-2 infection is the primary task. In this work, we first proposed the idea of activating CRISPR-Cas12a activity using double-stranded DNA amplified by a three-dimensional (3D) DNA walker. We applied it to the design of an electrochemiluminescent (ECL) biosensor to detect the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) gene. We first activated the cleavage activity of CRISPR-Cas12a by amplifying the target DNA into a segment of double-stranded DNA through the amplification effect of a 3D DNA walker. At the same time, we designed an MXene based ECL material: [email protected] 3 C 2 @AuNPs, and constructed an ECL biosensor to detect the RdRp gene based on this ECL material as a framework. Activated CRISPR-Cas12a cleaves the single-stranded DNA on the surface of this sensor and causes the ferrocene modified at one end of the DNA to move away from the electrode surface, increasing the ECL signal. The extent of the change in electrochemiluminescence reflects the concentration of the gene to be measured. Using this system, we detected the SARS-CoV-2 RdRp gene with a detection limit of 12.8 aM. This strategy contributes to the rapid and convenient detection of SARS-CoV-2-associated nucleic acids and promotes the clinical application of ECL biosensors based on CRISPR-Cas12a and novel composite materials.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Yaqin Zhang,Minyan Chen,Chengrong Liu,Jiaqi Chen,Xinyi Luo,Yingying Xue,Qiming Liang,Li Zhou,Yu Tao,Mingqiang Li,Di Wang,Jianhua Zhou,Jiasi Wang
The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called C as12a-assisted RT- LA MP/AuN P (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/μL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.
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