Viral Threats Research Articles

Inactivation of Pseudovirus Expressing the D614G Spike Protein Mutation using Nitric Oxide-Plasma Activated Water.

Variants of concern (VOCs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) exhibit high infectivity due to mutations, particularly in the spike protein, that facilitate enhanced binding of virus to human angiotensin-converting enzyme 2 (hACE2). The D614G mutation, situated in S1-domain, promotes the open conformation of spike protein, augmenting its interaction with hACE2. Activated water neutralizes pathogens by damaging biological molecules; however, its effect on mutated SARS-CoV-2 or VOCs requires further exploration. Here, the efficacy of nitric oxide (NOx)-plasma activated water (PAW) in inhibiting infections by SARS-CoV-2 pseudovirus expressing D614G-mutated spike protein is investigated, which serves as a model for mutated SARS-CoV-2. Results demonstrated high prevalence of D614G mutation in SARS-CoV-2 and its VOCs. NOx-PAW is non-toxic to cells at high concentration, inhibiting infection by 71%. Moreover, NOx-PAW induced structural changes in S1-domain of spike protein, reducing its binding affinity and lowering clathrin-mediated endocytosis-related gene expression. Additionally, in silico analysis revealed NOx species in NOx-PAW played key role in impairing S1-domain function of the mutated SARS-CoV-2 pseudovirus by interacting directly with it. Collectively, these findings reveal the potent inactivation ability of PAW against mutated SARS-CoV-2 and suggest its potential application in combating emerging variants of SARS-CoV-2 and other viral threats.

Detection and discovery of plant viruses in Disporopsis through high-throughput sequencing

BackgroundDisporopsis, a member of the Liliaceae family and a perennial herb, is predominantly cultivated in southwestern and southeastern China. Its rhizome, referred to as Zhugenqi, serves as a traditional Chinese medicinal herb for the treatment of bone injuries. However, viral diseases have emerged as a significant challenge in the cultivation of Disporopsis.ObjectiveThe aim of this study was to identify and characterize viruses present in diseased samples of Disporopsis spp. using high-throughput sequencing (HTS) and reverse transcription-polymerase chain reaction (RT-PCR) to enhance the understanding of the virome associated with Disporopsis and to inform diagnostic and control strategies for viral diseases in this plant.MethodsDiseased samples of Disporopsis spp. were subjected to HTS and RT-PCR for virus identification. A total of five viruses were detected, including three novel viruses and two known viruses. The novel viruses were provisionally named Disporopsis chlorotic stripe virus (DCSV), Disporopsis pernyi-associated partitivirus (DaPTV), and Disporopsis pernyi-associated lispi-like virus (DaLV). Sequence identity and phylogenetic analyses were performed to confirm the novelty and taxonomic placement of these viruses.ResultsDCSV exhibited polyprotein sequence identities ranging from 47.6% to 83.6% with other potyviruses, with the highest identity (83.6%) shared with Polygonatum kingianum virus 5 (PKgV5). DaLV shared an amino acid sequence identity of 34.59% with maize suscal virus (MSV), and DaPTV shared an identity of 76.18–85.10% with Paris alphapartitivirus (ParAPV). Phylogenetic analyses supported the potential classification of the three novel viruses as new members of their respective genera. Two isolates of polygonatum mosaic-associated virus 1 (PMaV1) were identified in Disporopsis for the first time, showing divergences of 96.33% and 98.86% from existing isolates. RT-PCR analysis of 67 Disporopsis field samples collected from four cities in China revealed that more than half of the samples tested positive for at least one of the five viruses. PMaV1 and DaLV were the most prevalent, detected in 22 and 34 out of the 67 samples, respectively. Other viruses were detected at low rates and/or had limited distribution.ConclusionThis study provides insights into the virome infecting Disporopsis and offers valuable information for the diagnosis and control of viral diseases in this plant. The identification of five viruses, including three potential new members of their respective genera, contributes to the understanding of the viral threats to Disporopsis cultivation.

Cellular Nanoparticles Treat Coronavirus Infection in Vivo.

Cellular nanoparticles (CNPs), which refer to nanoparticles coated with natural cell membranes, are promising for neutralizing pathological agents. Here, we use CNPs as a medical countermeasure against the infection of SARS-CoV-2 variants in an animal model. CNPs comprise polymeric cores coated with the plasma membranes of human macrophages. The resulting nanoparticles (MΦ-NPs) act as host cell decoys to intercept SARS-CoV-2 and block its cellular entry, thus inhibiting subsequent viral infection. Our findings indicate that MΦ-NPs bind to the spike proteins of SARS-CoV-2 variants in a dose-dependent manner and inhibit the infectivity of live viruses. In hamsters infected with SARS-CoV-2 variants, MΦ-NPs significantly reduce the viral burden in the lungs, demonstrating their effectiveness in inhibiting viral infectivity in vivo. Furthermore, MΦ-NPs are primarily taken up by alveolar macrophages without inducing noticeable adverse effects. Given the crucial role of macrophages in viral infections, MΦ-NPs present a promising approach to combating emerging viral threats.

Advancing CRISPR-Based Solutions for COVID-19 Diagnosis and Therapeutics.

Since the onset of the COVID-19 pandemic, a variety of diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as the gold standard. However, a significant challenge in COVID-19 diagnostics is the wide range of symptoms presented by patients, necessitating early and accurate diagnosis for effective management. Although RT-qPCR is a precise molecular technique, it is not immune to false-negative results. In contrast, CRISPR-based detection methods for SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, and specific, and they do not require sophisticated instruments. These methods also show promise for scalability, enabling diagnostic tests. CRISPR technology can be customized to target any genomic region of interest, making it a versatile tool with applications beyond diagnostics, including therapeutic development. The CRISPR/Cas systems provide precise gene targeting with immense potential for creating next-generation diagnostics and therapeutics. One of the key advantages of CRISPR/Cas-based therapeutics is the ability to perform multiplexing, where different sgRNAs or crRNAs can target multiple sites within the same gene, reducing the likelihood of viral escape mutants. Among the various CRISPR systems, CRISPR/Cas13 and CARVER (Cas13-assisted restriction of viral expression and readout) are particularly promising. These systems can target a broad range of single-stranded RNA viruses, making them suitable for the diagnosis and treatment of various viral diseases, including SARS-CoV-2. However, the efficacy and safety of CRISPR-based therapeutics must be thoroughly evaluated in pre-clinical and clinical settings. While CRISPR biotechnologies have not yet been fully harnessed to control the current COVID-19 pandemic, there is an optimism that the limitations of the CRISPR/Cas system can be overcome soon. This review discusses how CRISPR-based strategies can revolutionize disease diagnosis and therapeutic development, better preparing us for future viral threats.

The Case against compulsory vaccination: the failed arguments from risk imposition, tax evasion, ‘social liberty’, and the priority of life

Arguments for mandatory or compulsory vaccination must justify the coercive infringement of bodily integrity via the injection of chemicals that permanently affect a body’s inner constitution. Four arguments are considered. The allegedly libertarian argument declares unvaccinated persons a threat; accordingly, vaccination could take the form of justifiable defence of self and others. This argument conflates material and statistical threats. The harsh coercive measures permissible in defence against the former are not permissible in prevention of the latter. The argument from tax evasion claims that people can be permissibly coerced into bearing their fair financial burdens of community life and likens this to sharing burdens in the face of a viral threat. The argument fails to demonstrate that vaccination would be fair, permissible in spite of potential lethal side-effects, and sufficiently similar to taxation despite the categorical difference between temporary deprivation of money and permanent deprivation of one’s original inner bodily constitution. The argument from ‘social liberty’ claims that the loss of freedom due to mandatory vaccination is only apparent, namely outweighed by corresponding gains in freedom. This argument conflates freedom as the absence of coercion with freedom as the presence of options for action. It fails to give the former its due weight and to demonstrate that persons may be coerced into increasing the options of others. The argument from the priority of life elevates the protection of life to an absolute value. This is unwarranted and leads to counterintuitive implications. Without better arguments, mandatory vaccination must be rejected.

Combating Emerging Respiratory Viruses: Lessons and Future Antiviral Strategies

Emerging viral diseases, including seasonal illnesses and pandemics, pose significant global public health risks. Respiratory viruses, particularly coronaviruses and influenza viruses, are associated with high morbidity and mortality, imposing substantial socioeconomic burdens. This review focuses on the current landscape of respiratory viruses, particularly influenza and SARS-CoV-2, and their antiviral treatments. It also discusses the potential for pandemics and the development of new antiviral vaccines and therapies, drawing lessons from past outbreaks to inform future strategies for managing viral threats.

Broad-Spectrum Antiviral Agents against SARS-CoV-2 Variants Inhibit the Conserved Viral Protein Nsp1-RNA Interaction.

The ongoing global threats posed by COVID-19 pandemic, catalyzed by SARS-CoV-2, underscores the pressing need for effective antiviral strategies. The viral non-structural protein 1 (Nsp1) significantly influences pathogenicity by impeding host protein expression and enhancing viral RNA translation through its interaction with the stem-loop 1 (SL1) in the 5' untranslated region (UTR). We have developed a novel dual-luciferase reporter assay, designed to investigate the critical Nsp1-SL1 interaction, and identified P23E02 as a potential inhibitor. Our investigation, combining molecular docking studies and alanine mutagenesis, has unveiled that P23E02 disrupts Nsp1-40S ribosomal subunit interaction, liberating translational inhibition and empowering host antiviral responses. P23E02 exhibits antiviral efficacy against various sarbecoviruses, making it a promising candidate for combatting COVID-19 and related diseases. This study underscores the therapeutic potential of targeting the Nsp1/SL1 axis and lays the foundation for innovative antiviral interventions, ultimately fortifying global preparedness against future viral threats.

Broad‐Spectrum Antiviral Agents against SARS‐CoV‐2 Variants Inhibit the Conserved Viral Protein Nsp1–RNA Interaction

AbstractThe ongoing global threats posed by COVID‐19 pandemic, catalyzed by SARS‐CoV‐2, underscores the pressing need for effective antiviral strategies. The viral non‐structural protein 1 (Nsp1) significantly influences pathogenicity by impeding host protein expression and enhancing viral RNA translation through its interaction with the stem‐loop 1 (SL1) in the 5′ untranslated region (UTR). We have developed a novel dual‐luciferase reporter assay, designed to investigate the critical Nsp1–SL1 interaction, and identified P23E02 as a potential inhibitor. Our investigation, combining molecular docking studies and alanine mutagenesis, has unveiled that P23E02 disrupts Nsp1–40S ribosomal subunit interaction, liberating translational inhibition and empowering host antiviral responses. P23E02 exhibits antiviral efficacy against various sarbecoviruses, making it a promising candidate for combatting COVID‐19 and related diseases. This study underscores the therapeutic potential of targeting the Nsp1/SL1 axis and lays the foundation for innovative antiviral interventions, ultimately fortifying global preparedness against future viral threats.

Ejection of Real-Time Malicious Intrusion and Attacks in IoT Empowered Infrastructure

The project recognizes the pervasive threat of computer viruses, malware, and hostile attacks on computer networks, highlighting the critical role of intrusion detection as a proactive defense technology. The project introduces a novel approach based on deep learning to identify and mitigate cybersecurity vulnerabilities and breaches in IoT-driven cyber-physical systems, aiming for enhanced security measures. The project's objective is to elevate intrusion detection beyond the limitations of traditional systems by addressing issues like accuracy, detection effectiveness, and reducing false positives. This emphasizes the advancement and innovation in cybersecurity. To achieve the project's goals, the method employs a generative adversarial network, a cutting-edge deep learning technique. Additionally, it distinguishes itself by contrasting unsupervised and deep learning-based discriminative approaches, showcasing a comprehensive and effective approach to cybersecurity. In our project, we successfully implemented an ensemble method to boost predictive accuracy by integrating multiple individual models. Particularly noteworthy is the inclusion of a hybrid architecture, combining Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM), denoted as CNN+LSTM. This hybrid model achieved an impressive accuracy of 99% when applied to the KDD-Cup dataset, underscoring the efficacy of our ensemble technique for intrusion detection in IoT- based cybersecurity infrastructures.

Characterization of neural infection by Oropouche orthobunyavirus.

Oropouche fever is a re-emerging global viral threat caused by infection with Oropouche orthobunyavirus (OROV). While disease is generally self-limiting, historical and recent reports of neurologic involvement highlight the importance of understanding the neuropathogenesis of OROV. In this study, we characterize viral replication kinetics in neurons and microglia derived from immortalized, primary, and induced pluripotent stem cell-derived cells, which are all permissive to infection. We demonstrate that ex vivo rat brain slice cultures can be infected by OROV and produce antiviral cytokines and chemokines, including IL-6, TNF-α and IFN-β, which introduces an additional model to study viral kinetics in the central nervous system. These findings provide additional insight into OROV neuropathogenesis and in vitro modeling strategies for a newly re-emerging arbovirus.

Phytochemistry, Mechanisms, and Preclinical Studies of Echinacea Extracts in Modulating Immune Responses to Bacterial and Viral Infections: A Comprehensive Review.

Echinacea species, particularly Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida, are renowned for their immunomodulatory, antibacterial, and antiviral properties. This review explores the mechanisms by which echinacea herbal extracts modulate immune responses, focusing on their effects on both innate and adaptive immunity in bacterial and viral infections. Key bioactive compounds, such as alkamides, caffeic acid derivatives, flavonoids, and polysaccharides, contribute to these effects. These compounds enhance immune cell activity, including macrophages and natural killer cells, stimulating cytokine production and phagocytosis. The antibacterial activity of echinacea against respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila) and skin pathogens (Staphylococcus aureus, Propionibacterium acnes) is reviewed, as well as its antiviral efficacy against viruses like herpes simplex, influenza, and rhinovirus. Echinacea's potential as a complementary treatment alongside conventional antibiotics and antivirals is discussed, particularly in the context of antibiotic resistance and emerging viral threats. Challenges associated with variability in phytochemical content and the need for standardized extraction processes are also addressed. This review provides a comprehensive overview of echinacea's therapeutic potential and outlines future directions for research, including clinical trials and dosage optimization.

Assessing the Role of Bacterial Innate and Adaptive Immunity as Barriers to Conjugative Plasmids.

Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that restriction modification and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the selective advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist in the bacterial population for a certain period, restriction modification and CRISPR-Cas can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face extinction.

Novel hybrid deep learning based cyber security threat detection model with optimization algorithm

In order to continuously provide services to the company, the Internet of Things (IoT) connects the hardware, software, storing data, and applications that could be utilized as a new port of entry for cyber-attacks. The privacy of IoT is presently very vulnerable to virus threats and software piracy. Threats like this have the potential to capture critical data, harming businesses' finances and reputations. We have suggested a hybrid Deep Learning (DL) strategy in this study to identify malware-infected programs and files that have been illegally distributed over the IoT environment. To detect illegal content utilizing Source code (SC) duplication, the Adaptive TensorFlow deep neural network with Improved Particle Swarm Optimization (IPSO) is suggested. This novel hybrid strategy improves cyber security by fusing cutting-edge DL with optimization methods, providing more effective and accurate detection. With a strong solution for real-time threat identification, the model handles the complexity of contemporary cyberthreats. To highlight the significance of the proxy regarding the SC duplication, the noisy data is filtered using the tokenization and weighting feature approaches. After that, duplication in SC is found using a DL method. To look into software piracy, the dataset was gathered via Google Code Jam (GCJ). Additionally, using the visual representation of color images, the Enhanced Long Short-Term Memory (E-LSTM) was employed to identify suspicious actions in the IoT environment. The Maling dataset is used to gather the malware samples required for testing. The experimental findings show that, in terms of categorization, the suggested method for evaluating cybersecurity threats in IoT surpasses conventional approaches.

Cellular immunity to nucleoproteins (NP) of Crimean-Congo hemorrhagic fever virus (CCHFV) and Hazara Virus (HAZV).

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a globally significant vector-borne pathogen with no internationally-licensed preventative and therapeutic interventions. Hazara virus (HAZV), on the other hand, a related Orthonairovirus, has not been reported as a human pathogen. HAZV has been proposed as a surrogate model for studying CCHFV, bisosafety level 4 (BSL-4) agent. Previously, we investigated the humoral immune responses between NPs of these viruses and in this study, we extended the scrutiny to cellular immune responses elicited by NPs of CCHFV and HAZV. Here, mice were immunized with recombinant CCHFV NP and HAZV NP to evaluate the correlates of cell-mediated immunity (CMI). Delayed-type hypersensitivity (DTH) responses were assessed by challenging immunized mice with CCHFV-rNP or HAZV-rNP on the footpad and lymphocyte proliferation assays (LPAs) were performed by stimulating splenocytes in vitro with CCHFV-rNP or HAZV-rNP to compare cellular immune responses. In all test groups, strong DTH and LPA responses were detected against homologous and heterologous challenging antigens. To assess the cytokine response, an RT-qPCR -specific for cytokine mRNAs was utilized. Interestingly, CCHFV NP stimulated groups exhibited a significantly elevated mRNA level of interleukin 17A (IL-17) compared to HAZV NP, indicating a notable difference in immune responses. This study presents comparison between CMI elicited by NPs of CCHFV and HAZV and contributes to the understanding of a highly pathogenic virus, particularly in the context of the declaration of CCHFV by World Health Organization's (WHO) as a major viral threat to the world.

Zooming in and out: Exploring RNA Viral Infections with Multiscale Microscopic Methods.

RNA viruses, being submicroscopic organisms, have intriguing biological makeups and substantially impact human health. Microscopic methods have been utilized for studying RNA viruses at a variety of scales. In order of observation scale from large to small, fluorescence microscopy, cryo-soft X-ray tomography (cryo-SXT), serial cryo-focused ion beam/scanning electron microscopy (cryo-FIB/SEM) volume imaging, cryo-electron tomography (cryo-ET), and cryo-electron microscopy (cryo-EM) single-particle analysis (SPA) have been employed, enabling researchers to explore the intricate world of RNA viruses, their ultrastructure, dynamics, and interactions with host cells. These methods evolve to be combined to achieve a wide resolution range from atomic to sub-nano resolutions, making correlative microscopy an emerging trend. The developments in microscopic methods provide multi-fold and spatial information, advancing our understanding of viral infections and providing critical tools for developing novel antiviral strategies and rapid responses to emerging viral threats.

Inhibition of fish rhabdovirus demonstrates application prospect of two methylimidazole phenylpropanoid-based small molecules in aquaculture

Aquaculture faces significant challenges, notably spring viremia of carp (SVC) caused by spring viremia of carp virus (SVCV), which is particularly devastating due to its high mortality rates and rapid transmission among fish populations. This study introduces two novel methylimidazole phenylpropanoid-based small molecules, LML1013 and LML1014, synthesized for combating SVCV in aquaculture environments. Comprehensive in vitro and in vivo evaluations demonstrated that these compounds have potent antiviral activities against SVCV. They effectively inhibited SVCV replication in epithelioma papulosum cyprinid (EPC) cells and significantly reduced mortality rates in infected juvenile common carp. Further analyses revealed that daily administration of these compounds not only blocked SVCV replication but also stimulated the innate immune responses of the fish, thereby enhancing their overall resistance to viral infection. Notably, the antiviral efficacy was observed in a dose- and time-dependent manner without inducing cytotoxic effects, emphasizing their therapeutic potential. The stability of LML1013 and LML1014 in aquacultural water and their ability to prevent horizontal viral transmission were also confirmed, further supporting their feasibility as treatment options in aquaculture. Overall, the development of LML1013 and LML1014 provides a promising strategy for controlling SVCV outbreaks and enhancing the sustainability of fish farming operations. This approach offers significant implications for improving aquaculture biosecurity and effectively managing viral disease threats.

COVID-19 policy responses, social norms, and behavior change in MENA

ABSTRACT Inducing behavior change is a missing factor in the face of viral threats. We provide evidence from a natural experiment in 2020 on the effects of containment, closure, and economic policy responses to COVID-19 on change in human mobility behavior in the Middle East and North Africa (MENA) region and worldwide. We also examine how social norms, namely risk taking and patience, and institutional trust, could explain the heterogenous effects of policy responses on behavior change. Our results show that the stringency of containment and closure policies decreased human mobility in MENA and worldwide. Risk-averse populations and populations with low-time preference were more likely to pre act and lower their mobility independent of containment and closure policies. The effectiveness of risk communication in promoting positive mobility change increased by the level of institutional trust. Specifically in MENA, populations were less responsive to the actual disease risk and the public perception of that risk. Familiarity with COVID-19 induced negative behavior change among impatient populations. Economic support policies promoted strong positive mobility change among low-risk and high-time preference populations. Income support seems to be the effective economic policy response in low-income countries and debt relief the effective one in higher-income countries.

Navigating the Dynamic Landscape of SARS-CoV-2: The Dual Role of Neutralizing Antibodies, Variability in Responses, and Strategies for Adaptive Pandemic Control

The global pandemic sparked by the emergence of SARS-CoV-2 and its variants has imposed a substantial burden of morbidity and mortality. Central to the battle against these viral threats is the immune response, with a spotlight on the pivotal role played by neutralizing antibodies. This comprehensive review delves into current research, unravelling the dual functionality of neutralizing antibodies acting as formidable barriers to viral replication and crucial facilitators of adaptive immune memory. Beyond this dual purpose, the review illuminates the nuanced variability characterizing neutralizing antibody responses to SARS-CoV-2. Emphasizing the dynamic nature of these responses, the review advocates for the plausible challenges in targeted therapeutic interventions. This review also attempts to compare various vaccination approaches and their impact on SARS-CoV-2, as well as offer insights into various Omicron variations. Recognizing the ever-evolving viral landscape, this exploration underscores the necessity of flexible approaches to address the diverse challenges posed by SARS-CoV-2 and its variants, contributing valuable insights to the ongoing global efforts in pandemic mitigation and public health safeguarding.

Analyzing and Critically Evaluating the Problems of Antiviral Chemotherapy

Antiviral chemotherapy, an indispensable tool in combating viral infections, faces numerous challenges that often undermine its overall effectiveness and application. This review critically examines the multifaceted issues associated with antiviral chemotherapy, drawing on comprehensive data from NCBI, PubMed, and other reputable academic sources. The primary purpose of this research is to analyze and evaluate key problems such as the development of drug resistance, narrow therapeutic windows, limited spectrum of activity, toxicity, high costs, viral latency, and the complexities inherent in combination therapy. These challenges necessitate a delicate and strategic balance in the development, regulation, and application of antiviral drugs. The research methodology included an exhaustive review of peer-reviewed articles and clinical studies sourced from PubMed and NCBI databases, focusing on ten critical challenges in antiviral chemotherapy. The findings underscore the persistent issue of drug resistance, particularly in RNA viruses like HIV and hepatitis C, which demand ongoing innovation in antiviral drug design and implementation. Additionally, the analysis reveals the significant risks posed by the narrow therapeutic index of many antiviral drugs, which often increases the likelihood of adverse effects, thus limiting their safe and effective use. The study also highlights the formidable challenges posed by viral latency and the limited efficacy of current therapies against emerging and re-emerging viral threats. This research significantly contributes to the understanding of the inherent limitations in existing antiviral therapies and underscores the pressing need for more effective, accessible, and safe treatments. The practical significance lies in offering insights that could guide future research, clinical practice, and policy decisions, ultimately improving global health outcomes in the fight against viral diseases.

Interferon-stimulated genes and their antiviral activity against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic remains an international health problem caused by the recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of May 2024, SARS-CoV-2 has caused more than 775 million cases and over 7 million deaths globally. Despite current vaccination programs, infections are still rapidly increasing, mainly due to the appearance and spread of new variants, variations in immunization rates, and limitations of current vaccines in preventing transmission. This underscores the need for pan-variant antivirals and treatments. The interferon (IFN) system is a critical element of the innate immune response and serves as a frontline defense against viruses. It induces a generalized antiviral state by transiently upregulating hundreds of IFN-stimulated genes (ISGs). To gain a deeper comprehension of the innate immune response to SARS-CoV-2, its connection to COVID-19 pathogenesis, and the potential therapeutic implications, this review provides a detailed overview of fundamental aspects of the diverse ISGs identified for their antiviral properties against SARS-CoV-2. It emphasizes the importance of these proteins in controlling viral replication and spread. Furthermore, we explore methodological approaches for the identification of ISGs and conduct a comparative analysis with other viruses. Deciphering the roles of ISGs and their interactions with viral pathogens can help identify novel targets for antiviral therapies and enhance our preparedness to confront current and future viral threats.