Translation Inhibition Mediated by Interferon-Stimulated Genes during Viral Infections.

Viruses often pose a significant threat to the host through the exploitation of cellular machineries for their own benefit. In the context of immune responses, myriad host factors are deployed to target viral RNAs and inhibit viral protein translation, ultimately hampering viral replication. Understanding how "non-self" RNAs interact with the host translation machinery and trigger immune responses would help in the development of treatment strategies for viral infections. In this review, we explore how interferon-stimulated gene products interact with viral RNA and the translation machinery in order to induce either global or targeted translation inhibition.

The Antiviral Potential of Perilla frutescens: Advances and Perspectives.

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.

The Influence of Simulated Organic Matter on the Inactivation of Viruses: A Review.

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.

Antiviral Drug Discovery.

A vast and painful price has been paid in the battle against viruses in global health [...].

Decontamination Effect of Hypochlorous Acid Dry Mist on Selected Bacteria, Viruses, Spores, and Fungi as Well as on Components of Electronic Systems.

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.

Disinfection and post-disinfection conditions drive bacterial and viral evolution across the environment and host.

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.

Linear Mixed Model of Virus Disinfection by Free Chlorine to Harmonize Data Collected across Broad Environmental Conditions.

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.

Graphene-based materials as nanoplatforms for antiviral therapy and prophylaxis.

INTRODUCTION: The dramatic effects caused by viral diseases have prompted the search for effective therapeutic and preventive agents. In this context, 2D graphene-based nanomaterials (GBNs) have shown great potential for antiviral therapy, enabling the functionalization and/or decoration with biomolecules, metals and polymers, able to improve their interaction with viral nanoparticles. AREAS COVERED: This review summarizes the most recent advances of the antiviral research related to 2D GBNs, based on their antiviral mechanism of action. Their ability to inactivate viruses by inhibiting the entry inside cells, or through drug/gene delivery, or by stimulating the host immune response are here discussed. As reported, biological studies performed in vitro and/or in vivo allowed to demonstrate the antiviral activity of the developed GBNs, at different stages of the virus life cycle and the evaluation of their long-term toxicity. Other mechanisms closely related to the physicochemical properties of GBNs are also reported, demonstrating the potential of these materials for antiviral prophylaxis. EXPERT OPINION: GBNs represent valuable tools to fight emerging or reemerging viral infections. However, their translation into the clinic requires standardized scale-up procedures leading to the reliable and reproducible synthesis of these nanomaterials with suitable physicochemical properties, as well as more in-depth pharmacological and toxicological investigations. We believe that multidisciplinary approaches will give valuable solutions to overcome the encountered limitations in the application of GBNs in biomedical and clinical field.

Advances in bioinspired nanomaterials managing microbial biofilms and virulence: A critical analysis.

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.

HEX17(Neumifil): An intranasal respiratory biotherapeutic with broad-acting antiviral activity.

Broad-acting antiviral strategies to prevent respiratory tract infections are urgently required. Emerging or re-emerging viral diseases caused by new or genetic variants of viruses such as influenza viruses (IFVs), respiratory syncytial viruses (RSVs), human rhinoviruses (HRVs), parainfluenza viruses (PIVs) or coronaviruses (CoVs), pose a severe threat to human health, particularly in the very young or old, or in those with pre-existing respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD). Although vaccines remain a key component in controlling and preventing viral infections, they are unable to provide broad-spectrum protection against recurring seasonal infections or newly emerging threats. HEX17 (aka Neumifil), is a first-in-class protein-based antiviral prophylactic for respiratory viral infections. HEX17 consists of a hexavalent carbohydrate-binding module (CBM) with high affinity to sialic acids, which are typically present on terminating branches of glycans on viral cellular receptors. This allows HEX17 to block virus engagement of host receptors and inhibit infection of a wide range of viral pathogens and their variants with reduced risk of antiviral resistance. As described herein, HEX17 has demonstrated broad-spectrum efficacy against respiratory viral pathogens including IFV, RSV, CoV and HRV in multiple in vivo and in vitro studies. In addition, HEX17 can be easily administered via an intranasal spray and is currently undergoing clinical trials.

Advancements in Antiviral Drug Development: Comprehensive Insights into Design Strategies and Mechanisms Targeting Key Viral Proteins.

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.

In Silico Assessment of Chemical Disinfectants on Surface Proteins Unveiled Dissimilarity in Antiviral Efficacy and Suitability towards Pathogenic Viruses.

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.

An effective and rapidly degradable disinfectant from disinfection byproducts.

Chloroxylenol is a worldwide commonly used disinfectant. The massive consumption and relatively high chemical stability of chloroxylenol have caused eco-toxicological threats in receiving waters. We noticed that chloroxylenol has a chemical structure similar to numerous halo-phenolic disinfection byproducts. Solar detoxification of some halo-phenolic disinfection byproducts intrigued us to select a rapidly degradable chloroxylenol alternative from them. In investigating antimicrobial activities of disinfection byproducts, we found that 2,6-dichlorobenzoquinone was 9.0-22 times more efficient than chloroxylenol in inactivating the tested bacteria, fungi and viruses. Also, the developmental toxicity of 2,6-dichlorobenzoquinone to marine polychaete embryos decreased rapidly due to its rapid degradation via hydrolysis in receiving seawater, even without sunlight. Our work shows that 2,6-dichlorobenzoquinone is a promising disinfectant that well addresses human biosecurity and environmental sustainability. More importantly, our work may enlighten scientists to exploit the slightly alkaline nature of seawater and develop other industrial products that can degrade rapidly via hydrolysis in seawater.

Lectibodies as antivirals.

Growing concerns regarding the emergence of highly transmissible viral diseases highlight the urgent need to expand the repertoire of antiviral therapeutics. For this reason, new strategies for neutralizing and inhibiting these viruses are necessary. A promising approach involves targeting the glycans present on the surfaces of enveloped viruses. Lectins, known for their ability to recognize specific carbohydrate molecules, offer the potential for glycan-targeted antiviral strategies. Indeed, numerous studies have reported the antiviral effects of various lectins of both endogenous and exogenous origins. However, many lectins in their natural forms, are not suitable for use as antiviral therapeutics due to toxicity, other unfavorable pharmacological effects, and/or unreliable manufacturing sources. Therefore, improvements are crucial for employing lectins as effective antiviral therapeutics. A novel approach to enhance lectins' suitability as pharmaceuticals could be the generation of recombinant lectin-Fc fusion proteins, termed "lectibodies." In this review, we discuss the scientific rationale behind lectin-based antiviral strategies and explore how lectibodies could facilitate the development of new antiviral therapeutics. We will also share our perspective on the potential of these molecules to transcend their potential use as antiviral agents.

High-throughput microfluidic quantitative PCR system for the simultaneous detection of antibiotic resistance genes and bacterial and viral pathogens in wastewater.

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.

A comprehensive review on targeting cluster of differentiation: An attractive strategy for inhibiting viruses through host proteins.

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.

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview.

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.

The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies.

Interferons (IFNs) are antiviral cytokines that defend against viral infections by inducing the expression of interferon-stimulated genes (ISGs). Interferon-inducible transmembrane proteins (IFITMs) 1, 2, and 3 are crucial ISG products and members of the CD225 protein family. Compelling evidence shows that IFITMs restrict the infection of many unrelated viruses by inhibiting the virus-cell membrane fusion at the virus entry step via the modulation of lipid composition and membrane properties. Meanwhile, viruses can evade IFITMs' restrictions by either directly interacting with IFITMs via viral glycoproteins or by altering the native entry pathway. At the same time, cumulative evidence suggests context-dependent and multifaceted roles of IFITMs in modulating virus infections and cell signaling. Here, we review the diverse antiviral mechanisms of IFITMs, the viral antagonizing strategies, and the regulation of IFITM activity in host cells. The mechanisms behind the antiviral activity of IFITMs could aid the development of broad-spectrum antivirals and enhance preparedness for future pandemics.