RESUMEN
The laboratory diagnosis of antiviral resistance is a quickly changing field due to new drug availability, the sunsetting of older drugs, the development of novel technologies, rapid viral evolution, and the financial/logistic pressures of the clinical laboratory. This mini-review summarizes the current state of clinically available antiviral resistance testing in the United States in 2024, covering the most commonly used test methods, mechanisms, and clinical indications for herpes simplex virus, cytomegalovirus, human immunodeficiency virus, influenza, hepatitis B virus, and hepatitis C virus drug resistance testing. Common themes include the move away from phenotypic to genotypic methods for first-line clinical testing, as well as uncertainty surrounding the clinical meaningfulness of minority variant detection as next-generation sequencing methods have become more commonplace.
Asunto(s)
Antivirales , Farmacorresistencia Viral , Humanos , Farmacorresistencia Viral/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Pruebas de Sensibilidad Microbiana , Virosis/diagnóstico , Virosis/virología , Virosis/tratamiento farmacológico , Estados Unidos , Virus/efectos de los fármacos , Virus/genética , Genotipo , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
RNA capping is an essential trigger for protein translation in eukaryotic cells. Many viruses have evolved various strategies for initiating the translation of viral genes and generating progeny virions in infected cells via synthesizing cap structure or stealing the RNA cap from nascent host messenger ribonucleotide acid (mRNA). In addition to protein translation, a new understanding of the role of the RNA cap in antiviral innate immunity has advanced the field of mRNA synthesis in vitro and therapeutic applications. Recent studies on these viral RNA capping systems have revealed startlingly diverse ways and molecular machinery. A comprehensive understanding of how viruses accomplish the RNA capping in infected cells is pivotal for designing effective broad-spectrum antiviral therapies. Here we systematically review the contemporary insights into the RNA-capping mechanisms employed by viruses causing human and animal infectious diseases, while also highlighting its impact on host antiviral innate immune response. The therapeutic applications of targeting RNA capping against viral infections and the development of RNA-capping inhibitors are also summarized.
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Antivirales , Caperuzas de ARN , ARN Viral , Virosis , Animales , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Inmunidad Innata , Caperuzas de ARN/metabolismo , ARN Viral/genética , Virosis/tratamiento farmacológico , Virosis/inmunología , Replicación Viral/efectos de los fármacos , Virus/genética , Virus/efectos de los fármacos , Virus/inmunologíaRESUMEN
Microbial virulence and biofilm formation stand as a big concern against the goal of achieving a green and sustainable future. Microbial pathogenesis is the process by which the microbes (bacterial, fungal, and viral) cause illness in their respective host organism. 'Nanotechnology' is a state-of-art discipline to address this problem. The use of conventional techniques against microbial proliferation has been challenging against the environment. To tackle this problem, there has been a revolution in this multi-disciplinary field, to address the aspect of bioinspired nanomaterials in the antibiofilm and antimicrobial sector. Bioinspired nanomaterials prove to be a potential antibiofilm and antimicrobial agent as they are non-hazardous to the environment and mostly synthesized using a single-step reduction protocol. They exhibit synergistic effects against bacterial, fungal, and viral pathogens and thereby, control the virulence. In this literature review, we have elucidated the potential of bioinspired nanoparticles as well as nanomaterials as a promising anti-microbial treatment pedagogy and throw light on the advancements in how smart photo-switchable platforms have been designed to exhibit both bacterial releasing as well as bacterial-killing properties. Certain limitations and possible outcomes of these bio-based nanomaterials have been discussed in the hope of achieving a green and sustainable ecosystem.
Asunto(s)
Antiinfecciosos , Bacterias , Biopelículas , Nanoestructuras , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Virulencia , Nanoestructuras/química , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Antiinfecciosos/farmacología , Hongos/efectos de los fármacos , Hongos/patogenicidad , Nanotecnología/métodos , Nanopartículas/química , Humanos , Virus/efectos de los fármacosRESUMEN
Cancer, ranked as the second leading cause of mortality worldwide, leads to the death of approximately seven million people annually, establishing itself as one of the most significant health challenges globally. The discovery and identification of new anti-cancer drugs that kill or inactivate cancer cells without harming normal and healthy cells and reduce adverse effects on the immune system is a potential challenge in medicine and a fundamental goal in Many studies. Therapeutic bacteria and viruses have become a dual-faceted instrument in cancer therapy. They provide a promising avenue for cancer treatment, but at the same time, they also create significant obstacles and complications that contribute to cancer growth and development. This review article explores the role of bacteria and viruses in cancer treatment, examining their potential benefits and drawbacks. By amalgamating established knowledge and perspectives, this review offers an in-depth examination of the present research landscape within this domain and identifies avenues for future investigation.
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Bacterias , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Bacterias/efectos de los fármacos , Animales , Viroterapia Oncolítica , Virus/efectos de los fármacosRESUMEN
We develop a microscopic model of antibiotic diffusion in virus suspensions in a liquid crystalline state. We then approximate this with an effective homogenised model that is more amenable to analytical investigation, to understand the effect of charge on the antibiotic tolerance. We show that liquid crystalline virus suspensions slow down antibiotics significantly, and that electric charge strongly contributes to this by influencing the effective diameter and adsorptive capacity of the liquid crystalline viruses so that charged antibiotics diffuse much slower than neutral ones; this can be directly and efficiently derived from the homogenised model and is in good agreement with experiments in microbiology. Charge is also found to affect the relationship between antibiotic diffusion and viral packing density in a nontrivial way. The results elucidate the effect of charge on antibiotic tolerance in liquid crystalline biofilms in a manner that is straightforwardly extendable to other soft matter systems.
Asunto(s)
Antibacterianos , Cristales Líquidos , Adsorción , Antibacterianos/química , Antibacterianos/farmacología , Difusión , Cristales Líquidos/química , Suspensiones/química , Biopelículas/efectos de los fármacos , Virus/efectos de los fármacos , Virus/químicaRESUMEN
Despite the critical importance of virus disinfection by chlorine, our fundamental understanding of the relative susceptibility of different viruses to chlorine and robust quantitative relationships between virus disinfection rate constants and environmental parameters remains limited. We conducted a systematic review of virus inactivation by free chlorine and used the resulting data set to develop a linear mixed model that estimates chlorine inactivation rate constants for viruses based on experimental conditions. 570 data points were collected in our systematic review, representing 82 viruses over a broad range of environmental conditions. The harmonized inactivation rate constants under reference conditions (pH = 7.53, T = 20 °C, [Cl-] < 50 mM) spanned 5 orders of magnitude, ranging from 0.0196 to 1150 L mg-1 min-1, and uncovered important trends between viruses. Whereas common surrogate bacteriophage MS2 does not serve as a conservative chlorine disinfection surrogate for many human viruses, CVB5 was one of the most resistant viruses in the data set. The model quantifies the role of pH, temperature, and chloride levels across viruses, and an online tool allows users to estimate rate constants for viruses and conditions of interest. Results from the model identified potential shortcomings in current U.S. EPA drinking water disinfection requirements.
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Cloro , Desinfección , Cloro/farmacología , Inactivación de Virus/efectos de los fármacos , Virus/efectos de los fármacos , Desinfectantes/farmacologíaRESUMEN
AIMS: Airborne transmission of diseases presents a serious threat to human health, so effective air disinfection technology to eliminate microorganisms in indoor air is very important. This study evaluated the effectiveness of a non-thermal plasma (NTP) air disinfector in both laboratory experiments and real environments. METHODS AND RESULTS: An experimental chamber was artificially polluted with a bioaerosol containing bacteria or viruses. Additionally, classroom environments with and without people present were used in field tests. Airborne microbial and particle concentrations were quantified. A 3.0 log10 reduction in the initial load was achieved when a virus-containing aerosol was disinfected for 60 min and a bacteria-containing aerosol was disinfected for 90 min. In the field test, when no people were present in the room, NTP disinfection decreased the airborne microbial and particle concentrations (P < 0.05). When people were present in the room, their constant activity continuously contaminated the indoor air, but all airborne indicators decreased (P < 0.05) except for planktonic bacteria (P = 0.094). CONCLUSIONS: NTP effectively inactivated microorganisms and particles in indoor air.
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Microbiología del Aire , Contaminación del Aire Interior , Bacterias , Desinfección , Gases em Plasma , Desinfección/métodos , Contaminación del Aire Interior/prevención & control , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacos , Humanos , Gases em Plasma/farmacología , Aerosoles , Desinfectantes/farmacología , Virus/efectos de los fármacos , Virus/aislamiento & purificaciónRESUMEN
Comprehensive data on bacterial and viral pathogens of diarrhea and studies applying culture-independent methods for examining antibiotic resistance in wastewater are lacking. This study aimed to simultaneously quantify antibiotic resistance genes (ARGs), class 1 integron-integrase (int1), bacterial and viral pathogens of diarrhea, 16S rRNA, and other indicators using a high-throughput quantitative PCR (HT-qPCR) system. Thirty-six grab wastewater samples from a wastewater treatment plant in Japan, collected three times a month between August 2022 and July 2023, were centrifuged, followed by nucleic acid extraction, reverse transcription, and HT-qPCR. Fourteen targets were included, and HT-qPCR was performed on the Biomark X9™ System (Standard BioTools). For all qPCR assays, R2 was ≥0.978 and the efficiencies ranged from 90.5% to 117.7%, exhibiting high performance. Of the 36 samples, 20 (56%) were positive for Norovirus genogroup II (NoV-GII), whereas Salmonella spp. and Campylobacter jejuni were detected in 24 (67%) and Campylobacter coli in 13 (36%) samples, with mean concentrations ranging from 3.2 ± 0.8 to 4.7 ± 0.3 log10 copies/L. NoV-GII detection ratios and concentrations were higher in winter and spring. None of the pathogens of diarrhea correlated with acute gastroenteritis cases, except for NoV-GII, suggesting the need for data on specific bacterial infections to validate bacterial wastewater-based epidemiology (WBE). All samples tested positive for sul1, int1, and blaCTX-M, irrespective of season. The less explored blaNDM-1 showed a wide prevalence (>83%) and consistent abundance ranging from 4.3 ± 1.0 to 4.9 ± 0.2 log10 copies/L in all seasons. sul1 was the predominant ARG, whereas absolute abundances of 16S rRNA, int1, and blaCTX-M varied seasonally. int1 was significantly correlated with blaCTX-M in autumn and spring, whereas it showed no correlation with blaNDM-1, questioning the applicability of int1 as a sole indicator of overall resistance determinants. This study exhibited that the HT-qPCR system is pivotal for WBE.
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Aguas Residuales , Aguas Residuales/microbiología , Aguas Residuales/virología , Japón , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Farmacorresistencia Microbiana/genética , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , ARN Ribosómico 16S/análisis , ARN Ribosómico 16S/genética , Virus/genética , Virus/efectos de los fármacos , Virus/aislamiento & purificación , Microfluídica/métodosRESUMEN
A vast and painful price has been paid in the battle against viruses in global health [...].
Asunto(s)
Antivirales , Descubrimiento de Drogas , Antivirales/farmacología , Antivirales/uso terapéutico , Descubrimiento de Drogas/métodos , Humanos , Virosis/tratamiento farmacológico , Virus/efectos de los fármacosRESUMEN
This publication presents the effect of hypochlorous acid dry mist as a disinfectant on selected bacteria, viruses, spores, and fungi as well as on portable Microlife OXY 300 finger pulse oximeters and electronic systems of Raspberry Pi Zero microcomputers. The impact of hypochlorous acid on microbiological agents was assessed at concentrations of 300, 500, and 2000 ppm of HClO according to PN-EN 17272 (Variant I). Studies of the impact of hypochlorous acid fog on electronic components were carried out in an aerosol chamber at concentrations of 500 ppm and 2000 ppm according to two models consisting of 30 (Variant II) and 90 fogging cycles (Variant III). Each cycle included the process of generating a dry mist of hypochlorous acid (25 mL/m3), decontamination of the test elements, as well as cleaning the chamber of the disinfectant agent. The exposure of the materials examined on hypochlorous acid dry mist in all variants resulted in a decrease in the number of viruses, bacteria, spores, and fungi tested. In addition, the research showed that in the variants of hypochlorous acid fogging cycles analyzed, no changes in performance parameters and no penetration of dry fog of hypochlorous acid into the interior of the tested medical devices and electronic systems were observed.
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Descontaminación , Desinfectantes , Hongos , Ácido Hipocloroso , Ácido Hipocloroso/farmacología , Hongos/efectos de los fármacos , Desinfectantes/farmacología , Descontaminación/métodos , Bacterias/efectos de los fármacos , Virus/efectos de los fármacos , Esporas Fúngicas/efectos de los fármacos , Esporas Bacterianas/efectos de los fármacos , ElectrónicaRESUMEN
Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, the ligand-binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through an eco-pharmaco-economic analysis (EPEA). The results revealed that the binding affinities of chemical disinfectants to viral proteins varied significantly (p < 0.005). Rutin demonstrated promising broad-spectrum antiviral efficacy with an LBE of -8.49 ± 0.92 kcal/mol across all tested proteins. Additionally, rutin showed a superior eco-pharmaco-economic profile compared to the other chemicals, effectively balancing high antiviral effectiveness, moderate environmental impact, and affordability. These findings highlight rutin as a key phytochemical for use in remediating viral contaminants.
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Antivirales , Desinfectantes , Rutina , Desinfectantes/farmacología , Desinfectantes/química , Antivirales/farmacología , Antivirales/química , Rutina/química , Rutina/farmacología , Humanos , Simulación por Computador , Virus/efectos de los fármacos , Proteínas Virales/química , Proteínas Virales/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/química , Unión ProteicaRESUMEN
Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host's immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects.
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Antivirales , Compuestos Heterocíclicos , Antivirales/farmacología , Antivirales/química , Antivirales/uso terapéutico , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/química , Humanos , Replicación Viral/efectos de los fármacos , Relación Estructura-Actividad , Virus/efectos de los fármacos , Virosis/tratamiento farmacológico , AnimalesRESUMEN
Viruses pose a significant threat to human health, causing widespread diseases and impacting the global economy. Perilla frutescens, a traditional medicine and food homologous plant, is well known for its antiviral properties. This systematic review examines the antiviral potential of Perilla frutescens, including its antiviral activity, chemical structure and pharmacological parameters. Utilizing bioinformatics analysis, we revealed the correlation between Perilla frutescens and antiviral activity, identified overlaps between Perilla frutescens target genes and virus-related genes, and explored related signaling pathways. Moreover, a classified summary of the active components of Perilla frutescens, focusing on compounds associated with antiviral activity, provides important clues for optimizing the antiviral drug development of Perilla frutescens. Our findings indicate that Perilla frutescens showed a strong antiviral effect, and its active ingredients can effectively inhibit the replication and spread of a variety of viruses in this review. The antiviral mechanisms of Perilla frutescens may involve several pathways, including enhanced immune function, modulation of inflammatory responses, and inhibition of key enzyme activities such as viral replicase. These results underscore the potential antiviral application of Perilla frutescens as a natural plant and provide important implications for the development of new antiviral drugs.
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Antivirales , Perilla frutescens , Extractos Vegetales , Perilla frutescens/química , Antivirales/farmacología , Antivirales/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Replicación Viral/efectos de los fármacos , Virus/efectos de los fármacosRESUMEN
Water disinfection practices have long been established as a critical engineering intervention for controlling pathogen transmission and safeguarding individual and public health. However, recent discoveries have unveiled the significant role disinfection and post-disinfection play in accelerating the development of resistance to disinfectants and antimicrobial drugs within bacterial and viral communities in the environment. This phenomenon, in turn, may facilitate the emergence of persistent microbes and those with new genetic characteristics. These microbes may thrive in host environments with increased infectivity and resistance, posing challenges to current medical treatments and jeopardizing human health. In this perspective, we illuminate the intricate interplay between aquatic environments, microbes, and hosts and how microbial virulence evolves across the environment and host under the pressure of disinfection and post-disinfection conditions. We aim to draw attention to the previously overlooked potential risks associated with disinfection in driving the virulence evolution of bacteria and viruses, establish connections between pathogens in diverse environments and hosts within the overarching framework of the One Health concept, and ultimately provide guidelines for advancing future water disinfection technologies to effectively curb the spread of infectious diseases.
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Bacterias , Desinfectantes , Desinfección , Virus , Desinfección/métodos , Bacterias/genética , Bacterias/patogenicidad , Bacterias/efectos de los fármacos , Virus/genética , Virus/patogenicidad , Virus/efectos de los fármacos , Desinfectantes/farmacología , Humanos , Microbiología del Agua , Virulencia , Purificación del Agua/métodosRESUMEN
The disinfection of fabrics is crucial in preventing the spread of infectious diseases caused by pathogenic microorganisms to maintain public health. A previous study proved that plasma-activated nebulized mist (PANM) could effectively inactivate microorganisms both in aerosol and attached to the surface. In this study, the PANM driven by different plasma gases were employed to inactivate microorganisms on diverse fabrics. The PANM could efficiently inactivate a variety of microorganisms, including bacteria, fungi, and viruses, contaminating different fabrics, and even across covering layers of different fabrics. The mites residing on the cotton fabrics both uncovered and covered with various types of fabrics were also effectively inactivated by the PANM. After 30 times repeated treatments of the PANM, notable changes were observed in the color of several fabrics while the structural integrity and mechanical strength of the fabrics were unaffected and maintained similarly to the untreated fabrics with slight changes in elemental composition. Additionally, only trace amounts of nitrate remained in the fabrics after the PANM treatment. Therefore, the PANM treatment supplied an efficient, broad-spectrum, and environmentally friendly strategy for industrial and household disinfection of fabrics.
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Gases em Plasma , Textiles , Gases em Plasma/farmacología , Animales , Desinfección/métodos , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Nebulizadores y Vaporizadores , Virus/efectos de los fármacosRESUMEN
Viral infections continue to pose a significant global public health threat. Targeting host proteins, such as cluster of differentiation (CD) macromolecules, may offer a promising alternative approach to developing antiviral treatments. CDs are cell-surface biological macromolecules mainly expressed on leukocytes that viruses can use to enter cells, thereby evading immune detection and promoting their replication. The manipulation of CDs by viruses may represent an effective and clever means of survival through the prolonged co-evolution of hosts and viruses. Targeting of CDs is anticipated to hinder the invasion of related viruses, modulate the body's immune system, and diminish the incidence of subsequent inflammation. They have become crucial for biomedical diagnosis, and some have been used as valuable tools for resisting viral infections. However, a summary of the structures and functions of CDs involved in viral infection is currently lacking. The development of drugs targeting these biological macromolecules is restricted both in terms of their availability and the number of compounds currently identified. This review provides a comprehensive analysis of the critical role of CD proteins in virus invasion and a list of relevant targeted antiviral agents, which will serve as a valuable reference for future research in this field.
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Antivirales , Virosis , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Antivirales/química , Virosis/tratamiento farmacológico , Virosis/virología , Virus/efectos de los fármacos , Animales , Interacciones Huésped-PatógenoRESUMEN
Organoids have emerged as a powerful tool for understanding the biology of the respiratory, digestive, nervous as well as urinary system, investigating infections, and developing new therapies. This article reviews recent progress in the development of organoid and advancements in virus research. The potential applications of these models in studying virul infections, pathogenesis, and antiviral drug discovery are discussed.
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Organoides , Virosis , Organoides/virología , Humanos , Animales , Virosis/virología , Virosis/tratamiento farmacológico , Virus/efectos de los fármacos , Virus/patogenicidad , Virus/crecimiento & desarrollo , Virus/clasificación , Antivirales/farmacología , Antivirales/uso terapéutico , Descubrimiento de Drogas/métodosRESUMEN
Viruses impose a significant public health burden globally, and one of the key elements in controlling their transmission is the ability to inactivate them using disinfectants. However, numerous challenges to inactivating foodborne viruses exist due to inherent viral characteristics (such as recalcitrance to commonly used inactivation agents) and external factors (such as improper cleaning before application of inactivation agent, improper contact time, etc.). Given the potential for improper application of disinfectants (such as shorter than recommended contact time, improper disinfectant concentration, etc.), understanding the performance of a disinfectant in the presence of an organic load is important. To accomplish this, the introduction of simulated organic loads is often used when studying the efficacy of a disinfectant against different viruses. However, the different types of simulated organic loads used in foodborne virus inactivation studies or their relative effects on inactivation have not been reviewed. The purpose of this review is to survey different simulated organic load formulations used in studying foodborne virus inactivation, as well as present and compare the influence of these different formulations on viral inactivation. The findings included in this review suggest that many simulated organic load formulations can reduce disinfectants' efficacy against viruses. Based on the findings in this review, blood, particularly serum or feces, are among the most commonly used and efficacious forms of simulated organic load in many tests.
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Desinfectantes , Inactivación de Virus , Virus , Inactivación de Virus/efectos de los fármacos , Desinfectantes/farmacología , Virus/efectos de los fármacos , Humanos , Microbiología de Alimentos , Desinfección/métodos , Enfermedades Transmitidas por los Alimentos/prevención & control , Enfermedades Transmitidas por los Alimentos/virología , Compuestos Orgánicos/farmacología , Compuestos Orgánicos/químicaRESUMEN
Viral infectious diseases have always been a threat to human survival and quality of life, impeding the stability and progress of human society. As such, researchers have persistently focused on developing highly efficient, low-toxicity antiviral drugs, whether for acute or chronic infectious diseases. This article presents a comprehensive review of the design concepts behind virus-targeted drugs, examined through the lens of antiviral drug mechanisms. The intention is to provide a reference for the development of new, virus-targeted antiviral drugs and guide their clinical usage.