Pub Date : 2024-09-01Epub Date: 2024-06-24DOI: 10.1007/s40588-024-00229-6
Uxua Modrego Lopez, Md Mehedi Hasan, Brandon Havranek, Shahidul M Islam
Purpose of the review: SARS-CoV-2 undergoes genetic mutations like many other viruses. Some mutations lead to the emergence of new Variants of Concern (VOCs), affecting transmissibility, illness severity, and the effectiveness of antiviral drugs. Continuous monitoring and research are crucial to comprehend variant behavior and develop effective response strategies, including identifying mutations that may affect current drug therapies.
Recent findings: Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.
Summary: This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.
{"title":"SARS-CoV-2 Resistance to Small Molecule Inhibitors.","authors":"Uxua Modrego Lopez, Md Mehedi Hasan, Brandon Havranek, Shahidul M Islam","doi":"10.1007/s40588-024-00229-6","DOIUrl":"10.1007/s40588-024-00229-6","url":null,"abstract":"<p><strong>Purpose of the review: </strong>SARS-CoV-2 undergoes genetic mutations like many other viruses. Some mutations lead to the emergence of new Variants of Concern (VOCs), affecting transmissibility, illness severity, and the effectiveness of antiviral drugs. Continuous monitoring and research are crucial to comprehend variant behavior and develop effective response strategies, including identifying mutations that may affect current drug therapies.</p><p><strong>Recent findings: </strong>Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.</p><p><strong>Summary: </strong>This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.</p>","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"11 3","pages":"127-139"},"PeriodicalIF":3.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose of review: Bacterial infections and antibiotic resistance contribute to global mortality. Despite many infections being preventable and treatable, the lack of reliable and accessible diagnostic tools exacerbates these issues. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based diagnostics has emerged as a promising solution. However, the development of CRISPR diagnostics has often occurred in isolation, with limited integration of genomic data to guide target selection. In this review, we explore the synergy between bacterial genomics and CRISPR-based point-of-care tests (POCT), highlighting how genomic insights can inform target selection and enhance diagnostic accuracy.
Recent findings: We review recent advances in CRISPR-based technologies, focusing on the critical role of target sequence selection in improving the sensitivity of CRISPR-based diagnostics. Additionally, we examine the implementation of these technologies in resource-limited settings across Asia and Africa, presenting successful case studies that demonstrate their potential.
Summary: The integration of bacterial genomics with CRISPR technology offers significant promise for the development of effective point-of-care diagnostics.
{"title":"Integrating Genomic Data with the Development of CRISPR-Based Point-of-Care-Testing for Bacterial Infections.","authors":"Thanyapat Wanitchanon, Claire Chewapreecha, Chayasith Uttamapinant","doi":"10.1007/s40588-024-00236-7","DOIUrl":"https://doi.org/10.1007/s40588-024-00236-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Bacterial infections and antibiotic resistance contribute to global mortality. Despite many infections being preventable and treatable, the lack of reliable and accessible diagnostic tools exacerbates these issues. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based diagnostics has emerged as a promising solution. However, the development of CRISPR diagnostics has often occurred in isolation, with limited integration of genomic data to guide target selection. In this review, we explore the synergy between bacterial genomics and CRISPR-based point-of-care tests (POCT), highlighting how genomic insights can inform target selection and enhance diagnostic accuracy.</p><p><strong>Recent findings: </strong>We review recent advances in CRISPR-based technologies, focusing on the critical role of target sequence selection in improving the sensitivity of CRISPR-based diagnostics. Additionally, we examine the implementation of these technologies in resource-limited settings across Asia and Africa, presenting successful case studies that demonstrate their potential.</p><p><strong>Summary: </strong>The integration of bacterial genomics with CRISPR technology offers significant promise for the development of effective point-of-care diagnostics.</p>","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"11 4","pages":"241-258"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-07-27DOI: 10.1007/s40588-023-00202-9
Clinton Jones
Purpose of review: Numerous studies concluded stress (acute, episodic acute, or chronic) increases the incidence of human alpha-herpes virus 1 (HSV-1) reactivation from latency in neurons. This review will summarize how stress stimulates viral gene expression, replication, and reactivation from latency.
Recent findings: Stress (capital S) stress-mediated activation of the glucocorticoid receptor (GR) accelerates reactivation from latency, whereas a corticosteroid-specific antagonist impairs viral replication and reactivation from latency. GR and specific stress-induced cellular transcription factors also stimulate viral promoters that drive expression of key viral transcriptional regulators: infected cell protein 0 (ICP0), ICP4, ICP27 and viral tegument protein (VP16). Hence, GR is predicted to initially stimulate viral gene expression. GR-mediated immune-inhibitory functions are also predicted to enhance viral replication and viral spread.
Summary: Identifying cellular factors and viral regulatory proteins that trigger reactivation from latency in neurons may provide new therapeutic strategies designed to reduce the incidence of reactivation from latency.
综述的目的:大量研究认为,压力(急性、偶发性急性或慢性)会增加人类α-疱疹病毒1(HSV-1)从神经元潜伏期重新激活的发生率。本综述将总结压力是如何刺激病毒基因表达、复制和从潜伏期重新激活的:最近的研究发现:应激(大写字母 S)介导的糖皮质激素受体(GR)激活可加速潜伏期病毒的重新激活,而皮质激素特异性拮抗剂则会损害病毒复制和潜伏期病毒的重新激活。GR和特定压力诱导的细胞转录因子也会刺激病毒启动子,从而驱动关键病毒转录调节因子的表达:感染细胞蛋白0(ICP0)、ICP4、ICP27和病毒外壳蛋白(VP16)。因此,预计 GR 最初会刺激病毒基因的表达。小结:确定引发神经元潜伏期再活化的细胞因素和病毒调控蛋白可能会提供新的治疗策略,以降低潜伏期再活化的发生率。
{"title":"Intimate Relationship Between Stress and Human Alpha‑Herpes Virus 1 (HSV‑1) Reactivation from Latency.","authors":"Clinton Jones","doi":"10.1007/s40588-023-00202-9","DOIUrl":"10.1007/s40588-023-00202-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>Numerous studies concluded stress (acute, episodic acute, or chronic) increases the incidence of human alpha-herpes virus 1 (HSV-1) reactivation from latency in neurons. This review will summarize how stress stimulates viral gene expression, replication, and reactivation from latency.</p><p><strong>Recent findings: </strong>Stress (capital S) stress-mediated activation of the glucocorticoid receptor (GR) accelerates reactivation from latency, whereas a corticosteroid-specific antagonist impairs viral replication and reactivation from latency. GR and specific stress-induced cellular transcription factors also stimulate viral promoters that drive expression of key viral transcriptional regulators: infected cell protein 0 (ICP0), ICP4, ICP27 and viral tegument protein (VP16). Hence, GR is predicted to initially stimulate viral gene expression. GR-mediated immune-inhibitory functions are also predicted to enhance viral replication and viral spread.</p><p><strong>Summary: </strong>Identifying cellular factors and viral regulatory proteins that trigger reactivation from latency in neurons may provide new therapeutic strategies designed to reduce the incidence of reactivation from latency.</p>","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"1 1","pages":"236-245"},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48421532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.1007/s40588-023-00210-9
Surya Prakash Sharma, Sujata Dwivedi, Sunil Kumar, K. Dhama, A. K. Sharma
{"title":"Bacterial and Fungal Keratitis: Current Trends in Its Diagnosis and Management","authors":"Surya Prakash Sharma, Sujata Dwivedi, Sunil Kumar, K. Dhama, A. K. Sharma","doi":"10.1007/s40588-023-00210-9","DOIUrl":"https://doi.org/10.1007/s40588-023-00210-9","url":null,"abstract":"","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"13 2","pages":"266 - 278"},"PeriodicalIF":5.2,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139271310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-08DOI: 10.1007/s40588-023-00209-2
Bojana Stekovic, Karl Anderson, Delainey Lancaster, Evelyn Stuck, Tsebaot Getachew, Venugopal Mukku, Brian J. Dingmann
{"title":"Status of Drug Discovery in Wetlands Through a Lens of Bioprospecting for New Antimicrobials Being Produced by Microorganisms","authors":"Bojana Stekovic, Karl Anderson, Delainey Lancaster, Evelyn Stuck, Tsebaot Getachew, Venugopal Mukku, Brian J. Dingmann","doi":"10.1007/s40588-023-00209-2","DOIUrl":"https://doi.org/10.1007/s40588-023-00209-2","url":null,"abstract":"","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"9 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135392122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-20DOI: 10.1007/s40588-023-00208-3
Bianca B. Jütte, Luca Love, J. Peter Svensson
Abstract Purpose of Review The main obstacle to an HIV-1 cure is the reservoir of HIV-1 infected cells. While antiretroviral therapy (ART) eliminates the HIV-1 virus effectively, it does not target the reservoir. To eliminate infected cells, we need an improved understanding of the reservoir maintenance and reactivation mechanisms, including the influence of chromatin. Recent Findings The last years’ technological advances enable an in-depth study of the reservoir, uncovering subsets of infected cells, proviral integration sites, and single-cell nucleosome histone modifications. These revelations illustrate how the immune system and cell proliferation shape reservoirs under long-term ART. These forces create highly individual reservoirs that will require personalized treatment for their eradication. Summary A greater understanding of HIV-1 latency mechanisms, focusing on chromatin features, proviral reservoir dynamics, and inter-individual differences, can drive the development of more precise HIV-1 treatment strategies, ultimately achieving a globally available HIV-1 cure.
{"title":"Molecular Mechanisms of HIV-1 Latency from a Chromatin and Epigenetic Perspective","authors":"Bianca B. Jütte, Luca Love, J. Peter Svensson","doi":"10.1007/s40588-023-00208-3","DOIUrl":"https://doi.org/10.1007/s40588-023-00208-3","url":null,"abstract":"Abstract Purpose of Review The main obstacle to an HIV-1 cure is the reservoir of HIV-1 infected cells. While antiretroviral therapy (ART) eliminates the HIV-1 virus effectively, it does not target the reservoir. To eliminate infected cells, we need an improved understanding of the reservoir maintenance and reactivation mechanisms, including the influence of chromatin. Recent Findings The last years’ technological advances enable an in-depth study of the reservoir, uncovering subsets of infected cells, proviral integration sites, and single-cell nucleosome histone modifications. These revelations illustrate how the immune system and cell proliferation shape reservoirs under long-term ART. These forces create highly individual reservoirs that will require personalized treatment for their eradication. Summary A greater understanding of HIV-1 latency mechanisms, focusing on chromatin features, proviral reservoir dynamics, and inter-individual differences, can drive the development of more precise HIV-1 treatment strategies, ultimately achieving a globally available HIV-1 cure.","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"8 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-07DOI: 10.1007/s40588-023-00207-4
Marcella Cipelli, Eloísa Martins da Silva, Niels Olsen Saraiva Câmara
{"title":"Gut Microbiota Resilience Mechanisms Against Pathogen Infection and its Role in Inflammatory Bowel Disease","authors":"Marcella Cipelli, Eloísa Martins da Silva, Niels Olsen Saraiva Câmara","doi":"10.1007/s40588-023-00207-4","DOIUrl":"https://doi.org/10.1007/s40588-023-00207-4","url":null,"abstract":"","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"99 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135253345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29DOI: 10.1007/s40588-023-00204-7
Nancy Weiland-Bräuer
Abstract Purpose of Review Since the introduction of Archaea as a new domain of life more than 45 years ago, progress in their phylogenetic classification and knowledge of their exclusive biological characteristics has identified archaea as unique microorganisms which are widespread in extreme but also in various moderate ecosystems, including eukaryotic hosts. However, archaea are still neglected players within microbiomes, and research on archaea-bacteria interactions is still in its infancy due to methodological challenges. Recent Findings This review summarizes the current knowledge of archaea as components within microbiomes and focuses on their interactions with their bacterial neighbors and the principles of archaeal interactions. Summary Archaea are common constituents of animal and human microbiomes, which are dominated by Euryarchaeota. The gastrointestinal tract is the most studied body site, where archaea account for up to 4% of all microorganisms, primarily represented by methanogens. No archaeal pathogen has yet been identified, although methanogens are hypothesized to be indirectly involved in pathogenicity. Archaeal interactions comprise symbiotic relationships, and the cell membrane and wall might be as crucial as quorum sensing/quenching for these interactions. Particularly, syntrophic interactions under energy-deficiency stress seem to be an essential strategy for archaea. However, more research is urgently needed to discover how archaea sense their environment, compete with bacteria, and interact within complex microbiomes associated with multicellular organisms.
{"title":"Symbiotic Interactions of Archaea in Animal and Human Microbiomes","authors":"Nancy Weiland-Bräuer","doi":"10.1007/s40588-023-00204-7","DOIUrl":"https://doi.org/10.1007/s40588-023-00204-7","url":null,"abstract":"Abstract Purpose of Review Since the introduction of Archaea as a new domain of life more than 45 years ago, progress in their phylogenetic classification and knowledge of their exclusive biological characteristics has identified archaea as unique microorganisms which are widespread in extreme but also in various moderate ecosystems, including eukaryotic hosts. However, archaea are still neglected players within microbiomes, and research on archaea-bacteria interactions is still in its infancy due to methodological challenges. Recent Findings This review summarizes the current knowledge of archaea as components within microbiomes and focuses on their interactions with their bacterial neighbors and the principles of archaeal interactions. Summary Archaea are common constituents of animal and human microbiomes, which are dominated by Euryarchaeota. The gastrointestinal tract is the most studied body site, where archaea account for up to 4% of all microorganisms, primarily represented by methanogens. No archaeal pathogen has yet been identified, although methanogens are hypothesized to be indirectly involved in pathogenicity. Archaeal interactions comprise symbiotic relationships, and the cell membrane and wall might be as crucial as quorum sensing/quenching for these interactions. Particularly, syntrophic interactions under energy-deficiency stress seem to be an essential strategy for archaea. However, more research is urgently needed to discover how archaea sense their environment, compete with bacteria, and interact within complex microbiomes associated with multicellular organisms.","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135133102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}