Molecular and Cellular Probes最新文献

{"title":"Role of microRNAs in neutrophil extracellular trap formation and prevention: Systematic narrative review.","authors":"Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Goran Sedeeq Hama Faraj, Snur Rasool Abdullah, Seerwan Hamadameen Sulaiman, Hasan Pourmoshtagh, Mohammad Taheri","doi":"10.1016/j.mcp.2024.101986","DOIUrl":"10.1016/j.mcp.2024.101986","url":null,"abstract":"<p><p>Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included \"NETs,\" \"neutrophil extracellular traps,\" \"NETosis,\" \"miRNA,\" \"miR,\" and \"micro-RNA.\" The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans.</p>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":" ","pages":"101986"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy","authors":"Jian Wu ,&nbsp;Wenqiang Xu ,&nbsp;Jingchi Li ,&nbsp;Cheng Luo ,&nbsp;Bo Chen ,&nbsp;Luo Lin ,&nbsp;Tianyu Huang ,&nbsp;Tao Luo ,&nbsp;Lin Yang ,&nbsp;Jiexiang Yang","doi":"10.1016/j.mcp.2024.101988","DOIUrl":"10.1016/j.mcp.2024.101988","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6.</div></div><div><h3>Methods</h3><div>Firstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot.</div></div><div><h3>Results</h3><div>HKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6.</div></div><div><h3>Conclusions</h3><div>HKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101988"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFRSF11B promotes the progression of bladder cancer through PI3K/AKT signaling pathway","authors":"Hao Deng ,&nbsp;Jinzhuo Ning ,&nbsp;Yuan Ruan ,&nbsp;Weimin Yu ,&nbsp;Fan Cheng","doi":"10.1016/j.mcp.2024.101989","DOIUrl":"10.1016/j.mcp.2024.101989","url":null,"abstract":"<div><div>TNFRSF11B contributes to tumorigenesis in many malignancies. Nevertheless, its function and underlying tumorigenic mechanism in bladder cancer (BC) has been rare.</div><div>The clinical significance and relevant signaling pathway of TNFRSF11B in BC were assessed using bioinformatic analysis. The determination of TNFRSF11B expression was conducted in bladder tissues and BC cells. BC cells were subjected to functional experiments to evaluate their ability to proliferate, migrate, and invade. Cell apoptosis experiments were conducted. The protein levels of markers associated with epithelial-mesenchymal transition (EMT) and molecules linked to the PI3K/AKT pathway were assessed. To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized. TNFRSF11B exhibited significant upregulation in both BC tissues and various cell lines. Inhibited TNFRSF11B expression impeded the growth, movement, infiltration of BC cells. Conversely, the ultimate outcome varied when TNFRSF11B was overexpressed. In vivo assay further confirmed the above results. Furthermore, TNFRSF11B promoted malignant traits by controlling the PI3K/AKT pathway. In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101989"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The activation of SYNJ2/GRB2 axis accelerates the malignant metastasis and angiogenesis of gastric cancer cells","authors":"Weiwei Ning,&nbsp;Qingxu Yang,&nbsp;Zhengbiao Li,&nbsp;Ming Xie","doi":"10.1016/j.mcp.2024.101990","DOIUrl":"10.1016/j.mcp.2024.101990","url":null,"abstract":"<div><div>In gastric cancer (GC), tumor cell metastasis to lymph node may occur, and can be impacted by synaptojanin 2 (SYNJ2). Herein, we explored the mechanism of SYNJ2 in the progress of GC. SYNJ2 level in GC tissues was predicted by GEPIA database. After GC cells were transfected with short hairpin RNA against SYNJ2 (shSYNJ2), shGRB2, SYNJ2 overexpression plasmid and growth factor receptor-bound protein 2 (GRB2) overexpression plasmid, the mRNA levels of SYNJ2 and GRB2 in GC cells were quantified by qRT-PCR. CCK-8, flow cytometry, wound healing, transwell and tube formation assays were performed for detecting viability, apoptosis, migration, invasion and angiogenesis of GC cells. Protein levels of GRB2, vascular endothelial growth factor (VEGF), E-Cadherin, N-Cadherin and Vimentin in GC cells were measured by Western blot. The relationship between SYNJ2 and GRB2 was assessed by Co-immunoprecipitation (CO-IP) assay. SYNJ2 was highly expressed in GC tissues and cells. SYNJ2 overexpression promoted viability, migration, invasion, angiogenesis and GRB2 level, and inhibited apoptosis of GC cells, while shSYNJ2 exhibited opposite effects. GRB2 overexpression boosted yet shGRB2 suppressed cell migration, invasion and angiogenesis. Notably, SYNJ2 could interact with GRB2. GRB2 overexpression and shGRB2 reversed the effects of shSYNJ2 and overexpressed SYNJ2 on cell migration, invasion and angiogenesis and levels of metastasis-related proteins, respectively. In conclusion, SYNJ2 promotes GC cell metastasis and angiogenesis by up-regulating GRB2.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101990"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway","authors":"Ming Zhou ,&nbsp;Yaqi Zhang ,&nbsp;Qiong Zhang ,&nbsp;Yanchu Tong","doi":"10.1016/j.mcp.2024.101987","DOIUrl":"10.1016/j.mcp.2024.101987","url":null,"abstract":"<div><div>Thyroid cancer (TC) is the most common malignant tumor of the head and neck. As a common epigenetic modification in mRNAs, N6-methyladenosine (m6A) modification plays critical roles in biological process of cancers. However, m6A methyltransferase methyltransferase-like 14 (METTL14)-mediated m6A modification and its potential regulatory mechanisms in TC are not fully elucidated. In our study, we observed that METTL14 was decreased in TC tissues and cells. And upregulation of METTL14 induced apoptotic cell death and hampered cell proliferation, epithelial mesenchymal transition (EMT) and tumor growth <em>in vitro</em> and <em>in vivo</em>. Mechanistically, METTL14 increased the expression of suppressor of cytokine signaling 3 (SOCS3) through m6A methylation modification, and knockdown of SOCS3 reversed the inhibitory effect of overexpressing METTL14 on TC tumorigenesis. In addition, METTL14-mediated m6A modification of SOCS3 inactivated the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway, and in the METTL14-overexpressing TC cells, silencing SOCS3-induced upregulation of cell proliferation, EMT and suppression of apoptosis was reversed by JAK2/STAT3 inhibitor AG490 and WP1066. Together, we indicated that METTL14/m6A/SOCS3/JAK2/STAT3 axis play an important role in the progression of TC.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101987"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prospective role of lapatinib as an adjuvant therapy in prevalent cancers: Insights from in silico analysis targeting EGFR and HER2","authors":"Behnaz Dolatabadi ,&nbsp;Maryam Peymani ,&nbsp;Leila Rouhi ,&nbsp;Ali Salehzadeh ,&nbsp;Kiavash Hushmandi ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.mcp.2024.101985","DOIUrl":"10.1016/j.mcp.2024.101985","url":null,"abstract":"<div><h3>Introduction</h3><div>Various pieces of evidence suggest an elevation in the levels of EGFR and HER2 in different cancers leading to the proliferation, invasion, and metastasis of cancer cells. In this study, we conducted a comprehensive investigation into the expression alterations of these two receptors in various cancers using in silico data. In addition, we investigated the therapeutic potential of lapatinib as an inhibitor of these receptors in various cancer types.</div></div><div><h3>Methods</h3><div>RNAseq data for prevalent cancers were downloaded from The Cancer Genome Atlas (TCGA). After initial preprocessing, expression changes of HER2, EGFR, and candidate genes—identified based on their association with EGFR and HER2 signaling pathways—were examined. Human protein atlas data were utilized to assess the protein expression of HER2 and EGFR. GSE129254 was employed to identify molecular pathways and candidate genes associated with lapatinib. The protein-protein interaction network was used to identify lapatinib-influenced hub genes. Clinical data for common cancers were used to investigate the correlation between the expression of candidate genes and patients' mortality rates by Cox regression test.</div></div><div><h3>Results</h3><div>The findings clearly indicated a significant increase in the expression levels of HER2 and EGFR in cancers such as kidney, lung, breast, bladder, pancreas, head and neck, stomach, and endometrial, both at the mRNA and protein levels (p-value &lt;0.01). Additionally, more than 30 % of samples in some cancers showed a twofold increase in HER2 or EGFR expression. The analysis of GSE129254 data revealed that lapatinib reduces the expression of numerous genes associated with cell proliferation. METTL1, LYAR, LTV1, CCND1, NOP2, and DDX21 were identified as hub genes related to the effect of lapatinib. Our results demonstrated that many hub genes exhibited elevated expression in candidate cancers, and the upregulation of some of them was correlated with poor prognosis.</div></div><div><h3>Conclusion</h3><div>Our results indicate an upregulation in the expression levels of HER2 and EGFR in certain common cancers, suggesting that lapatinib, in addition to breast cancer, could be considered for the treatment of these cancers. Furthermore, we demonstrated that some genes with increased expression in prevalent cancers and associated with poor prognosis have the potential to be modulated by lapatinib.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101985"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into the potential of algorithms using AI technology as in vitro diagnostics utilizing microbial extracellular vesicles","authors":"Jinho Yang","doi":"10.1016/j.mcp.2024.101992","DOIUrl":"10.1016/j.mcp.2024.101992","url":null,"abstract":"<div><div>Recently, the microbiome has been gaining significant attention in the healthcare sector as a next-generation factor. However, there remains a substantial gap in our understanding of the fundamental mechanisms of microbes, particularly regarding the effector microbial products exchanged between the microbiota and the host. Consequently, research on microbial extracellular vesicles (MEVs) has increased. MEVs, which are nano-sized, can circulate throughout the body and penetrate the bloodstream, carrying diverse information. Consequently, they are increasingly being utilized in medical applications. Additionally, AI technologies are being utilized in medicine. The combination of MEVs and AI technology is being explored for the development of algorithm-based in vitro diagnostics (IVD). Therefore, this study aims to review the integration of MEVs and AI technology as diagnostic tools for personalized medicine. This paper reviewed the MEV-based algorithms developed by a variety of human samples and AI technology. Additionally, most of MEV-based diagnostic models showed higher clinical performance. Several important factors are crucial for accurate diagnosis. First, optimizing sample types according to specific diseases is essential. Second, AI technology with higher diagnostic power yields more accurate results. Finally, incorporating additional markers can enhance diagnostic power. However, applying this tool <em>in situ</em> faces several limitations, including method standardization, sample size, and analysis techniques. In the future, we anticipate that research on MEVs will advance our understanding of their role in disease and establish the foundation for precision medicine strategies.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101992"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer","authors":"Shaosheng Lou ,&nbsp;Wang Yang ,&nbsp;Qian Zhao ,&nbsp;Yunshan Ouyang ,&nbsp;Lingling Cao ,&nbsp;Chen Lin","doi":"10.1016/j.mcp.2024.101984","DOIUrl":"10.1016/j.mcp.2024.101984","url":null,"abstract":"<div><h3>Background</h3><div>The abnormal expression of circRNA may contribute to the progression of cervical cancer by influencing the biological processes.</div></div><div><h3>Aim</h3><div>This study aimed to identify the differentially expressed circRNAs in cervical cancer and validate the circ_0008193 ceRNA network in cervical cancer cells.</div></div><div><h3>Methods</h3><div>Using the absolute log2 value of fold change &gt;1 and <em>p</em>-value of &lt;0.05, the differentially expressed circRNAs were obtained from GSE102686 and GSE113696 from cervical cancer tissues and cervical cancer cells with the help of the GEO2R tool. Downstream miRNAs and mRNAs were predicted using relevant informatics databases. The circRNA-miRNA-mRNA interaction network was conducted with the assistance of Cytoscape. Circ_0008193-miR-182-5p-PTEN axis was validated with expression level and cell function using RT-qPCR, a dual-luciferase reporter assay, and cellular experiments.</div></div><div><h3>Results</h3><div>GSE102686 and GSE113696 databases overlapped 7 differentially expressed circRNAs and five circRNAs have the same expression pattern. Based on the literature and expression pattern, a circRNA-miRNA-mRNA network was conducted. The circ_0008193, miR-182-5p, and PTEN expression patterns were downregulation, upregulation, and downregulation, respectively. Overexpressed circ_0008193 suppressed proliferation, migration, and invasion of cervical cancer cells. MiR-182-5p diminished the inhibitory influence of circ_0008193 on cellular behaviors, while PTEN counteracted the effect of miR-182-5p.</div></div><div><h3>Conclusion</h3><div>This investigation revealed the existence of a circRNA-miRNA-mRNA network in cervical cancer, and preliminary verified the function of circ_0008193-miR-182-5p-PTEN axis in cervical cancer cells, which offers additional guidance on investigating the molecular mechanisms of cervical cancer.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101984"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA PCIF1 promotes aerobic glycolysis in A549/DDP cells by competitively binding miR-326 to regulate PKM expression","authors":"Wan Zhong ,&nbsp;Chun Wang ,&nbsp;Ye Sun","doi":"10.1016/j.mcp.2024.101977","DOIUrl":"10.1016/j.mcp.2024.101977","url":null,"abstract":"<div><h3>Objective</h3><p>Utilizing transcriptome analysis to investigate the mechanisms and therapeutic approaches for cisplatin resistance in non-small cell lung cancer (NSCLC).</p></div><div><h3>Methods</h3><p>Firstly, the biological characters of A549 cells and A549/DDP cells were detected by RNA sequencing, CCK-8 and hippocampal energy analyzer. Then, the differential Genes were functionally enriched by GO and KEGG and the competitive endogenous RNA network map was constructed. Finally, the effects of the predicted biogenesis pathway on the biological functions of A549/DDP cells were verified by in vitro and in vivo experiments.</p></div><div><h3>Result</h3><p>The differentially transcribed genes of A549 and A549/DDP cells were analyzed by enrichment analysis and cell biological characteristics detection. The results showed that A549/DDP cells showed significantly increased resistance to cisplatin, glucose metabolism signaling pathway and glycolysis levels compared with A549 cells. Among glycolysis-related transcription genes, PKM had the most significant difference Fold Change is 8. LncRNA PCIF1 is a new marker of A549/DDP cells and can be used as a molecular sponge to regulate the expression of PKM. LncRNA PCIF1 targets miR-326 to induce PKM expression, promote glycolysis level, and enhance the resistance of A549/DDP cells to cisplatin.</p></div><div><h3>Conclusion</h3><p>LncRNA PCIF1 as biomarkers of A549/DDP cells, higher expression can induce the PKM, promote cell glycolysis, lead to the occurrence of cisplatin resistance. LncRNA PCIF1 can be considered as a potential target for treating cisplatin-resistant NSCLC.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101977"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089085082400029X/pdfft?md5=f5d1e132c9ded44bf4ac17a2e707db00&pid=1-s2.0-S089085082400029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 replication and drug discovery","authors":"Farah Nazir ,&nbsp;Arnaud John Kombe Kombe ,&nbsp;Zunera Khalid ,&nbsp;Shaheen Bibi ,&nbsp;Hongliang Zhang ,&nbsp;Songquan Wu ,&nbsp;Tengchuan Jin","doi":"10.1016/j.mcp.2024.101973","DOIUrl":"10.1016/j.mcp.2024.101973","url":null,"abstract":"<div><p>The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people and continues to wreak havoc across the globe. This sudden and deadly pandemic emphasizes the necessity for anti-viral drug development that can be rapidly administered to reduce morbidity, mortality, and virus propagation. Thus, lacking efficient anti-COVID-19 treatment, and especially given the lengthy drug development process as well as the critical death tool that has been associated with SARS-CoV-2 since its outbreak, drug repurposing (or repositioning) constitutes so far, the ideal and ready-to-go best approach in mitigating viral spread, containing the infection, and reducing the COVID-19-associated death rate. Indeed, based on the molecular similarity approach of SARS-CoV-2 with previous coronaviruses (CoVs), repurposed drugs have been reported to hamper SARS-CoV-2 replication. Therefore, understanding the inhibition mechanisms of viral replication by repurposed anti-viral drugs and chemicals known to block CoV and SARS-CoV-2 multiplication is crucial, and it opens the way for particular treatment options and COVID-19 therapeutics. In this review, we highlighted molecular basics underlying drug-repurposing strategies against SARS-CoV-2. Notably, we discussed inhibition mechanisms of viral replication, involving and including inhibition of SARS-CoV-2 proteases (3C-like protease, 3CL^pro or Papain-like protease, PL^pro) by protease inhibitors such as Carmofur, Ebselen, and GRL017, polymerases (RNA-dependent RNA-polymerase, RdRp) by drugs like Suramin, Remdesivir, or Favipiravir, and proteins/peptides inhibiting virus-cell fusion and host cell replication pathways, such as Disulfiram, GC376, and Molnupiravir. When applicable, comparisons with SARS-CoV inhibitors approved for clinical use were made to provide further insights to understand molecular basics in inhibiting SARS-CoV-2 replication and draw conclusions for future drug discovery research.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101973"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000252/pdfft?md5=ce4435cfc161a5a1c58308335aa8f8a2&pid=1-s2.0-S0890850824000252-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}