Biological & pharmaceutical bulletin最新文献_第9页

Evaluating Signal Peptide Efficiency for Extracellular Protein Secretion for mRNA Vaccine Design. mRNA疫苗设计中细胞外蛋白分泌的信号肽效率评价

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00155

Shinya Sato, Naoki Minagawa, Yuro Hirata, Masanori Sasaki, Takumi Okamoto, Mariko Kamiya, Koji Matsuhisa, Shigeru Kawakami, Masayuki Kaneko

{"title":"Evaluating Signal Peptide Efficiency for Extracellular Protein Secretion for mRNA Vaccine Design.","authors":"Shinya Sato, Naoki Minagawa, Yuro Hirata, Masanori Sasaki, Takumi Okamoto, Mariko Kamiya, Koji Matsuhisa, Shigeru Kawakami, Masayuki Kaneko","doi":"10.1248/bpb.b25-00155","DOIUrl":"https://doi.org/10.1248/bpb.b25-00155","url":null,"abstract":"mRNA vaccines have emerged as promising platforms for the prevention of infectious diseases and cancer treatment. The antigenic protein has a signal peptide added to the N-terminus for extracellular secretion. However, it remains unclear whether the optimization of signal peptides has been sufficiently compared and examined for antigen protein secretion and immunogenicity. This study investigated the effects of various signal peptides on the extracellular secretion of a model protein, NanoLuc luciferase (Nluc), in different cell lines. We compared the secretion efficiency of Nluc fused to artificial (#38 and #34) and natural signal peptides (cystatin S, lactotransferrin, and tissue plasminogen activator) in human embryonic kidney 293, C2C12, and HepG2 cells. Luciferase assays and Western blot analysis revealed that the cystatin S signal peptide consistently induced the highest secretion of Nluc among all cell types tested. Notably, the cystatin S signal peptide outperformed previously reported tissue plasminogen activator signal peptides in terms of secretion efficiency. Furthermore, we observed no correlation between Nluc secretion and mRNA expression levels for each signal peptide, suggesting that enhanced secretion was not attributable to increased transcription. Our findings highlight the potential of the cystatin S signal peptide in enhancing the extracellular secretion of antigenic proteins in mRNA vaccines by improving the efficiency of protein translation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"706-712"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vaseline Coating on Paw Soles Alters the Spontaneous Gait of Rats. 脚掌涂敷凡士林改变大鼠自发步态。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00116

Yuga Kimura, Kotaro Yamashiro, Yuji Ikegaya, Nobuyoshi Matsumoto

引用次数: 0

Research Progress in Drug Development Based on Functional Molecules Involved in Pathogenesis and Analysis of Their Mechanisms. 基于功能分子参与发病机制的药物开发研究进展。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00069

Hideaki Hara

{"title":"Research Progress in Drug Development Based on Functional Molecules Involved in Pathogenesis and Analysis of Their Mechanisms.","authors":"Hideaki Hara","doi":"10.1248/bpb.b25-00069","DOIUrl":"https://doi.org/10.1248/bpb.b25-00069","url":null,"abstract":"Ocular diseases that result in blindness impair the QOL of patients as well as cause significant socioeconomic losses. Glaucoma is the leading cause of blindness, followed by retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration (AMD). Although the pathogeneses of these ocular diseases differ, they are all retinal diseases that lead to blindness owing to progressive retinal damage. However, the mechanisms underlying the pathogenesis and progression of these diseases have not yet been fully elucidated. In addition, treatment methods for these diseases have not yet been fully established, and their pathophysiology should be elucidated to establish novel treatment methods and drugs. Rodent pathological models, particularly mice and rats, have been established to elucidate the pathogenesis of these diseases. However, anatomical differences between the eyes of humans and rodents suggest that differences in pathogenic mechanisms may exist. In addition, species differences in drug responsiveness have become an issue in various respects, making it increasingly difficult to directly extrapolate the results obtained in rodents to humans. Therefore, evaluations using non-human primates, which are physiologically similar to humans, are required. This review outlines the basic research of AMD and glaucoma models using mice and non-human primates and their therapeutic strategies, focusing on the research findings.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"744-758"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer's Disease Model App^NL-P-F Mice. 补骨脂精提取物对老年痴呆症模型AppNL-P-F小鼠认知功能障碍的预防作用

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00773

Genki Hiramatsu, Reina Mizutani, Kazufumi Toume, Yosuke Inada, Masahito Sawahata, Daisuke Uta, Katsuko Komatsu, Toshiaki Kume

{"title":"Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer's Disease Model AppNL-P-F Mice.","authors":"Genki Hiramatsu, Reina Mizutani, Kazufumi Toume, Yosuke Inada, Masahito Sawahata, Daisuke Uta, Katsuko Komatsu, Toshiaki Kume","doi":"10.1248/bpb.b24-00773","DOIUrl":"10.1248/bpb.b24-00773","url":null,"abstract":"Oxidative stress and neuroinflammation accompanied by microglial activation are increased in Alzheimer's disease (AD) and contribute to the pathogenesis of AD. Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a master transcription factor that acts as an endogenous defense mechanism against oxidative stress and inflammation and is a potential target for preventing AD. Psoraleae Semen (PS) reportedly has antioxidant and anti-inflammatory effects. This study aimed to examine the effects of PS extract (PSE) on Nrf2 activation and prevention of cognitive dysfunction in AppNL-P-F AD model mice. The effects of PSE on antioxidant response element (ARE) activity and cytoprotection in PC12 cells and on microglial activation in BV-2 cells were evaluated. PSE showed high ARE activity and prevented 6-hydroxydopamine-induced cytotoxicity in PC12 cells. Moreover, PSE suppressed lipopolysaccharide-induced nitric oxide production in BV-2 cells. Oral administration of PSE prevented cognitive dysfunction in AppNL-P-F mice without affecting motor function. Our results support that PSE can contribute to the development of new preventive and therapeutic agents for AD focusing on Nrf2 activation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"75-79"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Involvement of the Na⁺/Ca²⁺ Exchanger in the Automaticity of the Cardiomyocytes from the Guinea Pig Pulmonary Vein but Not the Sinus Node. Na+/Ca2+交换参与豚鼠肺静脉而非窦结心肌细胞的自动性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00725

Ryosuke Odaka, Kana Sekiguchi, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka

{"title":"Involvement of the Na+/Ca2+ Exchanger in the Automaticity of the Cardiomyocytes from the Guinea Pig Pulmonary Vein but Not the Sinus Node.","authors":"Ryosuke Odaka, Kana Sekiguchi, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka","doi":"10.1248/bpb.b24-00725","DOIUrl":"10.1248/bpb.b24-00725","url":null,"abstract":"Fluorescence imaging analysis was performed in cardiomyocytes from the sinus node, the orthotopic pacemaker, and the pulmonary vein, a potential ectopic pacemaker that may cause atrial fibrillation, focusing on the role of the Na+/Ca2+ exchanger (NCX). Isolated cardiomyocytes from the guinea pig pulmonary vein and sinus node showing automaticity were loaded with fluorescence probes for analysis. Inhibition of NCX by SEA0400 decreased the Ca2+ transient frequency in the pulmonary vein cardiomyocytes but not in the sinus node. The basal intracellular Ca2+ concentration, as well as the number of Ca2+ sparks in the subsarcolemmal region, was higher in the pulmonary vein cardiomyocytes than in the sinus node. By contrast, the intracellular Na+ concentration was not different between the pulmonary vein and sinus node cardiomyocytes. The equilibrium potential for NCX (ENCX) was estimated to be less negative in the pulmonary vein cardiomyocytes than in the sinus node. In conclusion, the forward mode NCX is involved in spontaneous activity in the pulmonary vein cardiomyocytes but not in the sinus node; this is probably because the Ca2+ supply and the driving force for the forward mode NCX are both larger in the pulmonary vein cardiomyocytes than in the sinus node.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"151-161"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Piperacillin Exacerbates Vancomycin-Induced Toxicity in Renal Proximal Tubular Cells. 哌拉西林加重万古霉素诱导的肾近端小管细胞毒性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00726

Shingo Takada, Yuya Takashima, Riku Shinozaki, Mizuki Nishisato, Natsuko Takahashi-Suzuki, Akira Takaguri, Takehiro Yamada

{"title":"Piperacillin Exacerbates Vancomycin-Induced Toxicity in Renal Proximal Tubular Cells.","authors":"Shingo Takada, Yuya Takashima, Riku Shinozaki, Mizuki Nishisato, Natsuko Takahashi-Suzuki, Akira Takaguri, Takehiro Yamada","doi":"10.1248/bpb.b24-00726","DOIUrl":"https://doi.org/10.1248/bpb.b24-00726","url":null,"abstract":"Vancomycin (VCM) combined with piperacillin/tazobactam (PIPC/TAZ) is used as an empiric therapy in patients with severe infections, including sepsis. Recent research has found an increased incidence of acute kidney injury (AKI) in patients receiving combination therapy with these antibiotics. However, the pharmacological mechanism by which this combination worsens kidney function remains unclear. In this study, we investigated the direct cytotoxicity of VCM, PIPC, and TAZ on HK-2 cells and human renal proximal tubular epithelial cells (RPTEC). VCM, PIPC/TAZ, or PIPC significantly reduced cell viability in a concentration-dependent manner; the potency was in the order of VCM, PIPC/TAZ, and PIPC (IC50 values were 1717, 2491, and 3020 μg/mL, respectively). The combined treatment with PIPC/TAZ or PIPC significantly enhanced the VCM-induced decrease in cell viability. Furthermore, PIPC/TAZ or PIPC increased lactate dehydrogenase leakage, indicating membrane cytotoxicity, whereas no such effect was observed with VCM or TAZ. VCM increased caspase-3/-7 activity, whereas PIPC did not. The VCM-induced increase in neutrophil gelatinase-associated lipocalin (NGAL) production was amplified by concomitant PIPC treatment. Synergistic effects were detected for both the cell viability and NGAL production, suggesting that the direct toxicity of PIPC to RPTEC was responsible for the increased AKI incidence in patients treated with VCM. Our results may contribute to a better understanding of how AKI is exacerbated, as well as provide tips for preventing AKI after VCM and PIPC/TAZ combined therapy.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"363-371"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy of Enhanced Antimicrobial Stewardship Team Interventions for Patients Receiving Meropenem and Tazobactam/Piperacillin. 加强抗菌药物管理团队干预对接受美罗培南和他唑巴坦/哌拉西林治疗的患者的疗效。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00862

Kengo Ohashi, Yasutaka Shinoda, Tomoko Matsuoka, Kaori Arai, Nao Hotta, Takamasa Takahashi, Hiroaki Shikano, Michiko Kagajo, Tetsuya Yagi, Eiseki Usami

{"title":"Efficacy of Enhanced Antimicrobial Stewardship Team Interventions for Patients Receiving Meropenem and Tazobactam/Piperacillin.","authors":"Kengo Ohashi, Yasutaka Shinoda, Tomoko Matsuoka, Kaori Arai, Nao Hotta, Takamasa Takahashi, Hiroaki Shikano, Michiko Kagajo, Tetsuya Yagi, Eiseki Usami","doi":"10.1248/bpb.b24-00862","DOIUrl":"https://doi.org/10.1248/bpb.b24-00862","url":null,"abstract":"Multidrug-resistant bacteria pose a major challenge in healthcare, and antimicrobial stewardship teams (ASTs) play a crucial role in optimizing antimicrobial use, particularly for last-resort drugs like meropenem (MEPM) and tazobactam/piperacillin (TAZ/PIPC). This study evaluated the impact of enhanced interventions, which included a hospital-wide policy restricting MEPM and TAZ/PIPC use to 5 d and mandating pre-treatment culture testing. A before-and-after study was conducted at a public hospital in Japan, comparing the pre- (June 2021-May 2022) and post-enhanced intervention (June 2022-May 2023) periods. The primary outcome was days of therapy (DOT) per 1000 patient days for MEPM and TAZ/PIPC. Secondary outcomes included antimicrobial use density (AUD), monthly number of patients receiving MEPM and TAZ/PIPC, 30-d mortality, and AST intervention proposals. Overall, 1896 patients received MEPM (pre: 591; post: 527) or TAZ/PIPC (pre: 411; post: 367). As a result, MEPM DOT decreased from 19.4 to 17.2 per 1000 patient days (p = 0.019), and AUD from 14.4 to 11.7 defined daily doses per 1000 patient days (p = 0.017). TAZ/PIPC DOT remained unchanged (p = 0.219), while AUD decreased from 8.7 to 7.6 (p = 0.046). Furthermore, the monthly number of patients receiving MEPM and TAZ/PIPC and their 30-d mortality showed no significant change. AST proposals increased from 209 to 359 for MEPM and from 116 to 238 for TAZ/PIPC (both p < 0.001). In conclusion, enhanced interventions effectively reduced MEPM use without increasing TAZ/PIPC use or worsening 30-d mortality, suggesting that structured guidelines may enhance antimicrobial stewardship in resource-limited settings.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"571-576"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of Human Colorectal Cancer Cells in Tumor Spheroids by Sodium Butyrate. 丁酸钠调节人结直肠癌细胞在肿瘤球体中的作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00043

Yuzuki Takahama, An Kadoi, Yuno Tauchi, Satsuki Kasahara, Kyota Ishii, Tomohiro Yano

{"title":"Regulation of Human Colorectal Cancer Cells in Tumor Spheroids by Sodium Butyrate.","authors":"Yuzuki Takahama, An Kadoi, Yuno Tauchi, Satsuki Kasahara, Kyota Ishii, Tomohiro Yano","doi":"10.1248/bpb.b25-00043","DOIUrl":"10.1248/bpb.b25-00043","url":null,"abstract":"Butyrate exerts strong anti-colorectal cancer effects via epigenetic regulation. However, whether butyrate has a negative impact on colorectal cancer in vivo remains unclear. Therefore, this study aimed to investigate whether butyric acid can regulate the growth of colorectal cancer cells using spheroids as an in vivo model. A three-dimensional (3D) culture system was used to form spheroids from the human colorectal cancer cell line HT-29. Spheroids formed in the 3D culture system exhibited some malignant cancer phenotypes (increased cancer stem cell marker levels, anticancer drug resistance, and G0/G1 phase accumulation in the cell cycle) compared with cells in the two-dimensional cell culture system. Sodium butyrate (SB) treatment suppressed cancer stem cell marker levels in spheroids and induced differentiation by increasing the alkaline phosphatase activity. Additionally, SB-induced changes in genes related to cell cycle control indicated that SB reactivated the cell cycle in spheroids, regulating the transition from the G0 to G1 phase. Furthermore, SB treatment induced cell death via apoptosis, which might be due to G1 arrest in the cell cycle. In conclusion, SB induced the differentiation and subsequent cell death of HT-29-derived cancer cells in spheroids, highlighting its potential as a novel anticancer agent for colorectal cancer.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"872-877"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatic GSTP1/2 Exhibits High Sensitivity to Testosterone-Mediated Regulation in Mice. 小鼠肝脏GSTP1/2对睾酮介导的调节具有高度敏感性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00082

Youngseo Park, Ki-Hoan Nam, Herin Hwang, Se-Yeong Jeon, Doug-Young Ryu

{"title":"Hepatic GSTP1/2 Exhibits High Sensitivity to Testosterone-Mediated Regulation in Mice.","authors":"Youngseo Park, Ki-Hoan Nam, Herin Hwang, Se-Yeong Jeon, Doug-Young Ryu","doi":"10.1248/bpb.b25-00082","DOIUrl":"https://doi.org/10.1248/bpb.b25-00082","url":null,"abstract":"Glutathione S-transferases (GSTs) are essential phase II detoxification enzymes encoded by a diverse gene superfamily. Among them, the pi class (GSTP) includes 2 isozymes, GSTP1 and GSTP2, which share a high degree of sequence similarity. In mice, hepatic GSTP1/2 expression is higher in males than in females. To investigate the regulatory mechanisms underlying this sex difference, we examined orchiectomized mice treated with testosterone. Orchiectomy reduced hepatic GSTP1/2 expression and associated enzyme activity, both of which were restored following testosterone administration. To assess the sensitivity of GSTP1/2 to testosterone fluctuations, we compared mice experiencing a serum testosterone surge with those maintaining baseline levels. Mice with elevated testosterone exhibited increased hepatic GSTP1/2 protein expression and enzyme activity, demonstrating the high responsiveness of GSTP1/2 to testosterone. To our knowledge, this is the first study to demonstrate that testosterone surges regulate both the expression and enzymatic function of a specific protein. These findings underscore testosterone's critical role in the male-dominant expression of GSTP1/2 and highlight its sensitivity to physiological fluctuations in testosterone levels. Further studies are warranted to elucidate the molecular mechanisms by which testosterone surges influence gene expression.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"830-834"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of FDA-Approved Drugs That Inhibit SARS-CoV-2 and Human Norovirus Replication. fda批准的抑制SARS-CoV-2和人类诺如病毒复制的药物鉴定

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00236

Tsuyoshi Hayashi, Junki Hirano, Kosuke Murakami, Yoshiki Fujii, Sakura Kobayashi, Takashi Tanikawa, Masashi Kitamura, Yuichi Someya

{"title":"Identification of FDA-Approved Drugs That Inhibit SARS-CoV-2 and Human Norovirus Replication.","authors":"Tsuyoshi Hayashi, Junki Hirano, Kosuke Murakami, Yoshiki Fujii, Sakura Kobayashi, Takashi Tanikawa, Masashi Kitamura, Yuichi Someya","doi":"10.1248/bpb.b25-00236","DOIUrl":"https://doi.org/10.1248/bpb.b25-00236","url":null,"abstract":"In this study, to identify novel compounds that inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication by targeting its protease, we screened an U.S. Food and Drug Administration (FDA)-approved drug library to determine their effects on SARS-CoV-2 3CL protease (3CLpro) activity using a cellular- and green fluorescent protein (GFP) reporter-based 3CLpro assay, called the FlipGFP-3CLpro assay. Among the hit compounds, 5 compounds (auranofin, endoxifen, netupitant, pimozide, and regorafenib) were selected for further analysis. We found that 3 compounds (auranofin, endoxifen, and pimozide) showed dose-dependent inhibition of 3CLpro activity using both the FlipGFP-3CLpro assay and fluorescence-based in vitro 3CLpro assays. We then tested the effect of these compounds on SARS-CoV-2 replication in cultured cells and found that all 5 compounds inhibited viral replication in a dose-dependent manner. Interestingly, 4 of them, except for auranofin, significantly suppressed human norovirus (HuNoV) replication in human intestinal organoids. In brief, we identified several FDA-approved drugs that inhibit SARS-CoV-2 and HuNoV replication, which warrant further investigation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"994-1000"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0