{"title":"Exploring Niclosamide as a Multi-target Drug Against SARS-CoV-2: Molecular Dynamics Simulation Studies on Host and Viral Proteins.","authors":"Prachi Jagtap, Virendra Kumar Meena, Susmit Sambhare, Atanu Basu, Priya Abraham, Sarah Cherian","doi":"10.1007/s12033-024-01296-2","DOIUrl":"10.1007/s12033-024-01296-2","url":null,"abstract":"<p><p>Niclosamide has emerged as a promising repurposed drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In vitro studies suggested that niclosamide inhibits the host transmembrane protein 16F (hTMEM16F), crucial for lipid scramblase activity, which consequently reduces syncytia formation that aids viral spread. Based on other in vitro reports, niclosamide may also target viral proteases such as papain-like protease (PLpro) and main protease (Mpro), essential for viral replication and maturation. However, the precise interactions by which niclosamide interacts with these multiple targets remain largely unclear. Docking and molecular dynamics (MD) simulation studies were undertaken based on a homology model of the hTMEM16F and available crystal structures of SARS-CoV-2 PLpro and Mpro. Niclosamide was observed to bind stably throughout a 400 ns MD simulation at the extracellular exit gate of the hTMEM16F tunnel, forming crucial interactions with residues spanning the TM1-TM2 loop (Gln350), TM3 (Phe481), and TM5-TM6 loop (Lys573, Glu594, and Asp596). Among the SARS-CoV-2 proteases, niclosamide was found to interact effectively with conserved active site residues of PLpro (Tyr268), exhibiting better stability in comparison to the control inhibitor, GRL0617. In conclusion, our in silico analyses support niclosamide as a multi-targeted drug inhibiting viral and host proteins involved in SARS-CoV-2 infections.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3858-3873"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Bhoomika, Shubham Rajaram Salunkhe, A R Sakthi, T Saraswathi, S Manonmani, M Raveendran, M Sudha
{"title":"Correction: CRISPR-Cas9: Unraveling Genetic Secrets to Enhance Floral and Fruit Traits in Tomato.","authors":"S Bhoomika, Shubham Rajaram Salunkhe, A R Sakthi, T Saraswathi, S Manonmani, M Raveendran, M Sudha","doi":"10.1007/s12033-024-01336-x","DOIUrl":"10.1007/s12033-024-01336-x","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"4011"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Shi, Lei Cao, Daxiong Ding, Wenxing Yu, Ping Lv, Ning Yu
{"title":"Correction: Effects of Noise Damage on the Purinergic Signal of Cochlear Spiral Ganglion Cells in Guinea Pigs.","authors":"Min Shi, Lei Cao, Daxiong Ding, Wenxing Yu, Ping Lv, Ning Yu","doi":"10.1007/s12033-025-01432-6","DOIUrl":"10.1007/s12033-025-01432-6","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"4017-4019"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R Thirumalaisamy, S Vasuki, S M Sindhu, T M Mothilal, V Srimathi, B Poornima, M Bhuvaneswari, Mohan Hariharan
{"title":"Correction: FDA-Approved Chimeric Antigen Receptor (CAR)-T Cell Therapy for Different Cancers-A Recent Perspective.","authors":"R Thirumalaisamy, S Vasuki, S M Sindhu, T M Mothilal, V Srimathi, B Poornima, M Bhuvaneswari, Mohan Hariharan","doi":"10.1007/s12033-025-01495-5","DOIUrl":"10.1007/s12033-025-01495-5","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"4020"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanotechnology and CRISPR/Cas-Mediated Gene Therapy Strategies: Potential Role for Treating Genetic Disorders.","authors":"Guneet Kaur, Jasnoor Arora, Abhinashi Singh Sodhi, Sonu Bhatia, Navneet Batra","doi":"10.1007/s12033-024-01301-8","DOIUrl":"10.1007/s12033-024-01301-8","url":null,"abstract":"<p><p>Gene therapy has made substantial progress in the treatment of the genetic diseases, focussing on the reduction of characteristics of recessive/dominant disorders, as well as various cancers. Extensive research has been conducted in the past few decades to investigate the application of nanotechnology and CRISPR/Cas technology in gene therapy. Nanotechnology due to attributes such has targeted drug delivery, controlled release, scalability and low toxicity has gained attention of the medical world. CRISPR/Cas9 system is considered as an impactful genome editing tool in the area of next-generation therapeutics and molecular diagnostics. CRISPR technology emphasises on gene editing, gene regulation modulation, and formulation of defined genetic changes. Its applications in treatment of the genetic disorders are extended beyond traditional therapies. These techniques are being explored as treatment of several genetic disorders including Duchenne muscular dystrophy, cystic fibrosis, Alzheimer's disease, Parkinson's disease, and Huntington disease. Despite considerable therapeutic potential of gene therapy, several obstacles must be addressed before it can be widely adopted in clinical practice, particularly in terms of ensuring safety and effectiveness. As research advances in this captivating field, these therapies will become the primary treatments and will have significant beneficial effects on the lives of patients with genetic disorders.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3800-3822"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-10-01Epub Date: 2024-10-14DOI: 10.1007/s12033-024-01298-0
Yihong Guo, Lujing Chen, Qiulin Ma, Peiyu Liu
{"title":"Exosomal miR-494 Regulates the Biological Behavior of Trophoblasts by Targeting mTOR in Unexplained Recurrent Spontaneous Abortion.","authors":"Yihong Guo, Lujing Chen, Qiulin Ma, Peiyu Liu","doi":"10.1007/s12033-024-01298-0","DOIUrl":"10.1007/s12033-024-01298-0","url":null,"abstract":"<p><p>Recurrent spontaneous abortion (RSA) is a pregnancy disorder, and trophoblasts are involved in its complex pathogenesis. This study aimed to identify the functional role of exosomal miR-494 in promoting the development of unexplained RSA (uRSA). 15 uRSA tissues and 15 healthy controls were collected to compare the exosomal miR-494 expression. The ultracentrifugation method was used for serum exosome isolation, and exosome characteristics were examined using transmission electron microscopy (TEM). The affection of exosomal miR-494 on HTR-8/SVneo cells were determined by CCK-8, EdU, Wound healing, and Transwell assays. Our findings demonstrated that miR-494 levels were markedly lower in placental tissue and plasma exosomes from patients with uRSA than in normal pregnant women. Furthermore, treatment with miR-494-overexpressing exosomes reduced the viability, invasion, and migration of HTR-8/SVneo cells. In terms of regulation, exosomal miR-494 downregulated mTOR levels in HTR-8/SVneo cells. Mechanism research suggested that exosomal miR-494 reduces the viability, invasion, and migration of trophoblasts by targeting mTOR. Exosomal miR-494 and mTOR are potential predicative biomarkers and therapeutic targets for uRSA patients.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3898-3905"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment the Efficacy of the CRISPR System for Inducing Mutations in the AIMP2 Gene to Create a Cell Line Model of HLD17 Disease.","authors":"Shima Farrokhi, Atieh Eslahi, Farzaneh Alizadeh, Mohammad Amin Kerachian, Majid Mojarrad","doi":"10.1007/s12033-024-01257-9","DOIUrl":"10.1007/s12033-024-01257-9","url":null,"abstract":"<p><p>Hypomyelinating leukodystrophy-17 is a neurodevelopmental disorder caused by autosomal recessive mutations in the AIMP2 gene, resulting in a lack of myelin deposition during brain development, leading to variable neurological symptoms. Research on brain function in these disorders is challenging due to the lack of access to brain tissue. To overcome this problem, researchers have utilized different cell and animal models. The CRISPR-Cas9 system is considered the most optimal and effective method for genetic modification and developing cell models. We studied the efficacy of the CRISPR-Cas9 technology in inducing mutations in the AIMP2 gene in HEK293 cell lines. The study involved transfecting HEK293 cells with recombinant PX458 plasmids targeting spCas-9 and AIMP2 sgRNA. The cells were evaluated using fluorescent microscopy and enriched using serial dilution. The CRISPR/Cas9 plasmids were validated through PCR and Sanger sequencing. After serial dilution, AS-PCR, Sanger sequencing, and TIDE program analysis showed the construct successfully induces an indel mutation in HEK cells. Our findings demonstrated the great efficacy of the CRISPR system and produced a construct for inducing mutations in the AIMP2 gene, which can be utilized to edit the AIMP2 gene in nerve cells and create a cellular model of the HLD17 disease.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3922-3929"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-10-01Epub Date: 2024-10-24DOI: 10.1007/s12033-024-01299-z
Shulin Song, Donghui Gan, Di Wu, Ting Li, Shiqian Zhang, Yibo Lu, Guanqiao Jin
{"title":"Molecular Indicator for Distinguishing Multi-drug-Resistant Tuberculosis from Drug Sensitivity Tuberculosis and Potential Medications for Treatment.","authors":"Shulin Song, Donghui Gan, Di Wu, Ting Li, Shiqian Zhang, Yibo Lu, Guanqiao Jin","doi":"10.1007/s12033-024-01299-z","DOIUrl":"10.1007/s12033-024-01299-z","url":null,"abstract":"<p><p>The issue of multi-drug-resistant tuberculosis (MDR-TB) presents a substantial challenge to global public health. Regrettably, the diagnosis of drug-resistant tuberculosis (DR-TB) frequently necessitates an extended period or more extensive laboratory resources. The swift identification of MDR-TB poses a particularly challenging endeavor. To identify the biomarkers indicative of multi-drug resistance, we conducted a screening of the GSE147689 dataset for differentially expressed genes (DEGs) and subsequently conducted a gene enrichment analysis. Our analysis identified a total of 117 DEGs, concentrated in pathways related to the immune response. Three machine learning methods, namely random forest, decision tree, and support vector machine recursive feature elimination (SVM-RFE), were implemented to identify the top 10 genes according to their feature importance scores. A4GALT and S1PR1, which were identified as common genes among the three methods, were selected as potential molecular markers for distinguishing between MDR-TB and drug-susceptible tuberculosis (DS-TB). These markers were subsequently validated using the GSE147690 dataset. The findings suggested that A4GALT exhibited area under the curve (AUC) values of 0.8571 and 0.7121 in the training and test datasets, respectively, for distinguishing between MDR-TB and DS-TB. S1PR1 demonstrated AUC values of 0.8163 and 0.5404 in the training and test datasets, respectively. When A4GALT and S1PR1 were combined, the AUC values in the training and test datasets were 0.881 and 0.7551, respectively. The relationship between hub genes and 28 immune cells infiltrating MDR-TB was investigated using single sample gene enrichment analysis (ssGSEA). The findings indicated that MDR-TB samples exhibited a higher proportion of type 1 T helper cells and a lower proportion of activated dendritic cells in contrast to DS-TB samples. A negative correlation was observed between A4GALT and type 1 T helper cells, whereas a positive correlation was found with activated dendritic cells. S1PR1 exhibited a positive correlation with type 1 T helper cells and a negative correlation with activated dendritic cells. Furthermore, our study utilized connectivity map analysis to identify nine potential medications, including verapamil, for treating MDR-TB. In conclusion, our research identified two molecular indicators for the differentiation between MDR-TB and DS-TB and identified a total of nine potential medications for MDR-TB.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3946-3959"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}