Virus Activity Research Articles

Antiviral Effects and Mechanisms of Active Ingredients in Tea

Viruses play a significant role in human health, as they can cause a wide range of diseases, from mild illnesses to severe and life-threatening conditions. Cellular and animal experiments have demonstrated that the functional components in tea, such as catechins, theaflavins, theanine, and caffeine, exhibit significant inhibitory effects on a diverse array of viruses, including influenza, rotavirus, hepatitis, HPV, and additional types. The inhibition mechanisms may involve blocking virus–host recognition, interfering with viral replication, enhancing host immune responses, and inhibiting viral enzyme activity. This article reviews the research progress on the antiviral effects of tea’s functional components and their related mechanisms, hoping to contribute to future studies in this field.

Influenza A(H5N1) Virus Resilience in Milk after Thermal Inactivation.

Highly pathogenic avian influenza A(H5N1) detected in dairy cows raises concerns about milk safety. The effects of pasteurization-like temperatures on influenza viruses in retail and unpasteurized milk revealed virus resilience under certain conditions. Although pasteurization contributes to viral inactivation, influenza A virus, regardless of strain, displayed remarkable stability in pasteurized milk.

Application of sodium hypochlorite for human norovirus and hepatitis A virus inactivation in groundwater.

In this study, the effect of sodium hypochlorite (10-200 ppm of Cl2) on the inactivation of human norovirus (HuNV) GII.4 and hepatitis A virus (HAV) in groundwater was investigated using propidium monoazide (PMA)/reverse transcription quantitative real-time PCR (RT-qPCR). Initially, 4.00 log10 genome copies/μL of HuNV GII.4 or 5.50 log10 genome copies/μL of HAV were artificially inoculated in groundwater. The titers of HuNV GII.4 and HAV decreased significantly (P < 0.05) with increasing Cl2 concentrations. Groundwater was treated with 10, 30, 50, 100, 150, and 200 ppm of Cl2, and the viable HuNV GII.4 was significantly (P < 0.05) reduced to 3.28 (0.21-log reduction), 3.18 (0.31-log reduction), 3.01 (0.48 log reduction), 2.75 (0.74 log reduction), 2.54 (0.95 log reduction), and 2.34 (1.15 log reduction) log10 genome copies/μL, respectively. The viable HAV was also significantly (P < 0.05) reduced to 4.99 (0.23 log reduction), 4.76 (0.46 log reduction), 4.55 (0.67 log reduction), 4.21 (1.01-log reduction), 3.89 (1.33 log reduction), and 3.64 (1.58 log reduction) log10 genome copies/μL, respectively. The decimal reduction times (D values) (1-log10 genome reduction) of HuNV GII.4 and HAV infectivity in groundwater were predicted as 116.7 and 98.9 ppm of Cl2, respectively, using the first-order kinetics model (HuNV GII.4: y = -0.0054x + 3.3585, correlation coefficient (R2) = 0.97; HAV: y = -0.0091x + 5.0470, R2 = 0.97). The result specifically suggests that 150- to 200-ppm Cl2 can potentially be used for the inactivation of >1-log10 genome copy/μL HuNV GII.4 and HAV in groundwater.IMPORTANCEGroundwater represents a vital component of the global water supply, serving as a crucial source of potable water for humans. It serves as a source of potable water for up to 50% of the global population and accounts for 43% of all water used for irrigation. It thus follows that the sustainable management of groundwater represents a pivotal solution. However, the regrowth of pathogens in water that is not treated with chlorine or where proper residual chlorine is not maintained represents a risk to public health.

Efficacy of Disinfectants for Monkeypox Virus Inactivation on High Touch Surface Materials in Low-Resource Settings.

Disinfection efficacy tests were conducted on surface carriers inoculated with the monkeypox virus (MPXV) by applying six disinfectant solutions (and three controls) on six surfaces common in low-resource settings: four nonporous surfaces (stainless steel, glass, plastic, and latex) and two porous surfaces (ceramic and wood). Disinfectants were wiped on carriers in triplicate, with a 1 min contact time: 0.05 and 0.5% sodium hypochlorite, 70% ethanol, two quaternary ammonium compound (QAC)-based disinfectants, and 1.4% hydrogen peroxide. MPXV was then quantified, and log10 removal values were calculated. Sodium hypochlorite (0.05 and 0.5%) and ethanol (70%) removed MPXV to below detection level, ≥ 99.97% reduction for nonporous surfaces, and ≥99.40% for wood, QAC-based disinfectants were efficacious on nonporous surfaces (≥99.97% inactivation) but had diminished efficacy on wood, a porous surface, and 1.4% H2O2 had limited efficacy across all tested surfaces. Results varied by disinfectant type and surface type. Based on our results, we recommend using 0.05% sodium hypochlorite or 70% ethanol with 1 min contact time to inactive MPXV on clean nonporous and porous surfaces. As MPXV is evolving, future research with additional disinfectants, application methods, and environmental conditions and research to understand adsorption, disinfection efficacy, and transmission risk on porous surfaces are needed to develop practical disinfection recommendations.

Wpływ polimorfizmu genetycznego na przebieg oraz ciężkość zakażenia wirusem SARS-CoV-2 oraz choroby COVID-19

COVID-19 is severe respiratory and systemic disease with complex pathogenesis and many clinical symptoms, including symptoms from respiratory system, immunology system, cardio-vascular system, haematopoietic system and neurological system. Severe character of the disease is associated with occurrence of respiratory failure, septic shock, multiple organ dysfunctions syndrome, which can lead to patients death due to cardiac arrest. Knowledge about interactions between the virus and human proteins as well as knowledge of immunological mechanisms against infection is a key to identifying the area of virus activity and severity factors of COVID-19. Multiple variants of genes encoding proteins involved in host cell invasion by SARS-CoV-2 virus have been identified: ACE2 i TMPRSS2, TMPRSS11A (HGNC:27954), ELANE (HGNC:3309) oraz CTSL (HGNC:2537), IL-6 rs1800795 variant associated with an increased risk of COVID-19, variant rs35705950:G&gt;T located in the promoter of the MUC5B gene (11p15.5), encoding a protein that plays a key role in maintaining the proper function of the bronchoalveolar epithelium, having a protective effect against the form of the disease requiring hospitalization of the patient, as well as GC rs2282679 gene variant in the vitamin D binding protein associated with a more severe course of COVID-19. 48 of these variants were proved to be directly specific for some populations. Novel techniques of genome analysis enabled the research of the impact of specific polymorphism variants on the severity of various diseases including, COVID-19. Genetic factors analysis can permit understanding of disease pathogenesis, which is a chance to find effective treatment and prevention methods. Collected data from literature indicate that, in the case of COVID-19 disease, there are genes polymorphisms which affect the severity course.

Sequential activation of ERα-AMPKα signaling by the flavonoid baicalin down-regulates viral HNF-dependent HBV replication.

Baicalin (BA), a natural component found in many traditional Chinese medicines, exerts protective effects against several viruses. Although our previous studies have revealed that the anti-hepatitis B virus (anti-HBV) activity of BA depends on hepatocyte nuclear factor (HNF) signaling, the specific mechanisms remain unclear. The present study explored the potential signaling mechanisms involved in BA-mediated HBV suppression. Transcriptomic analysis suggested that BA significantly modulates the estrogen receptor (ER) and AMPK signaling pathways in HepG2 cells. The ER alpha (ERα) binding affinity of BA and its estrogen-like agonist activity were subsequently verified through molecular docking assays, BA-ERα affinity detection experiments, ERα luciferase reporter gene assays, and qRT-PCR. ERα knockdown (shRNA) and AMPK inhibition (Compound C and doxorubicin [Dox]) experiments revealed that the sequential activation of the ERα-LKB1-AMPK-HNF signaling axis is essential for the anti-HBV effects of BA. This study indicates that BA may trigger the ERα-AMPKα-HNF pathway to inhibit HBV replication, providing insights into its potential protective mechanisms against other viruses.

INFLUENCE OF PHYSICOCHEMICAL FACTORS ON THE SARS-COV-2 STRAIN ISOLATED FROM A DOG

This article presented the results of a study on the impact of physicochemical factors on the biological activity of the SARS-CoV-2 coronavirus isolated from a dog in the Republic of Kazakhstan. The results indicated that storing the virus at a temperature of -70°C led to a decrease in viral activity, similar to the effect observed when stored at room temperature. Storage at +40°C resulted in complete inactivation of the virus. The study on the effect of various concentrations of ionic and non-ionic detergents revealed that exposure to the ionic detergent DOC at concentrations of 0.1% and 0.5% caused a decrease in viral activity, while no change was observed at a concentration of 0.01%. The detergent SDS, at concentrations of 0.01%, 0.1%, and 0.5%, reduced the biological activity of the virus from the initial titer (5.25 lg TCID50/cm³) to 4.00 lg TCID50/cm³. Similarly, the use of non-ionic detergents, Triton X-100 and Tween-20, led to a reduction in viral activity from the initial titer to 4.50 lg TCID50/cm³. The effect of pH in acidic, neutral, and alkaline environments on the biological activity of the virus was also studied. A decrease in viral activity was observed at acidic and alkaline pH levels, whereas a neutral pH environment had no impact on viral activity.

Microbial distribution in Mudbank regions off Alappuzha, South-West coast of India.

The coastal waters of Kerala, in the South Eastern Arabian Sea (SEAS), are unique during the Southwest monsoon season due to the concurrent occurrence of two physical processes, the upwelling and Mudbanks. However, little is known about the viral ecology and activity in a system where upwelling and Mudbanks coexist, though it is generally recognized that microbial assemblages play a vital role in the food web dynamics of marine systems, particularly in upwelling. Water samples were taken from monsoon and pre-monsoon period from three locations, (M1, M2, and M3) off Alappuzha, on the southwest coast of India to examine the viral activity and distribution. The dissolved oxygen levels showed the incursion of hypoxic waters in all the stations during the peak upwelling period. Upwelling signals were prominent in all the stations, but Mudbank and upwelling co-occurred at M2 alone during monsoon. The abundance of viruses ranged from 0.86 to 15.68 × 106 Viral-like Particles (VLPs mL-1) and prokaryotic abundance ranged from 2.73-16.26 × 105 cells mL-1. Viral and prokaryotic abundance was significantly higher in the monsoon compared to pre and late-monsoon. Based on Transmission electron microscopy (TEM) results, the non-tailed viruses constituted the major (43%) proportion of the total viruses in this study region. However, the viral production rates and viral-mediated bacterial mortality were high in the pre-monsoon compared to the monsoon and late-monsoon periods. There was no obvious effect of Mudbanks on viral dynamics and the observed variations in virological and hydrological features were governed mainly by coastal upwelling.

Anti-dengue viral activity of Glycyrrhiza glabra roots in Vero cells

Despite being a global public health problem, there are no antiviral agents for dengue. Plants are the sources of most approved drugs and many phytochemicals have exhibited in vitro antiviral activity. We explored the antiviral potential of the aqueous extract of Glycyrrhiza glabra roots (GGaq) on dengue viruses. Plaque reduction antiviral assay for half maximal inhibitory concentrations (IC50) was done in Vero cells infected with dengue serotypes 1–4 and exposed to varying concentrations of GGaq. Half-maximal cytotoxic concentration (CC50) of the GGaq was 651.9 µg/mL. The IC50 of the four dengue serotypes (10–50 µg/mL) indicated moderate inhibition by GGaq. 98–100% inhibition of all dengue serotypes was seen with GGaq at the maximum nontoxic dose. Preparative thin layer chromatography of GGaq, isolated sub fractions E and F which had low to moderate antiviral activity (IC50 12.65–85.95 and IC50 13.14–69.27 respectively). They exhibited good therapeutic potential only for dengue serotype-4. Virus adsorption to cells was significantly inhibited by GG (50%) and sub fraction E (24.9%). Chloroquine diphosphate was used as the positive control in all assays. The aqueous extract of GG was non-toxic and had better antiviral activity than sub fractions E and F.

A LANA peptide inhibits tumor growth by inducing CHD4 protein cleavage and triggers cell death.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, and viral genes are poised to be transcribed in the latent chromatin. In the poised chromatins, KSHV latency-associated nuclear antigen (LANA) interacts with cellular chromodomain-helicase-DNA-binding protein 4 (CHD4) and inhibits viral promoter activation. CHD4 is known to regulate cell differentiation by preventing enhancers from activating promoters. Here, we identified a putative CHD4 inhibitor peptide (VGN73) from the LANA sequence corresponding to the LANA-CHD4 interaction surface. The VGN73 interacts with CHD4 at its PHD domain with a dissociation constant (KD) of 14nM. Pre-treatment with VGN73 enhanced monocyte differentiation into macrophages and globally altered the repertoire of activated genes in U937 cells. Furthermore, the introduction of the peptide into the cancer cells induced caspase-mediated CHD4 cleavage, triggered cell death, and inhibited tumor growth in a xenograft mouse model. The VGN73 may facilitate cell differentiation therapy.

The results of vaccination against novel coronavirus infection in adolescents with allergic diseases

Novel coronavirus infection requires analyzing its course in patients with allergic diseases. Patients with atopic allergic diseases remain insufficiently studied with regard to the peculiarities of the course of both the underlying allergic disease and infectious processes caused by viruses and bacteria. Epithelial cells in bronchial asthma do not respond sufficiently to interferons, suggesting that SARS-CoV-2 infection may suppress spontaneous upregulation of angiotensin-converting enzyme expression, which ultimately reduces disease severity, but at the same time makes patients with allergic atopic diseases susceptible to other viral infections. The results obtained indicate statistically significant differences in the formation of anti-RBD IgG antibodies to SARS-CoV-2 between the group of adolescents with bronchial asthma vaccinated against a new coronavirus infection and those not vaccinated against it. During the follow-up period after 6 months, a statistically significant increase in anti-RBD IgG titer to SARS-CoV-2 due to novel coronavirus infection was observed among the unimmunized children. Clinical parameters indicated a favorable course of atopic process and control of bronchial asthma exacerbations in adolescents who received vaccination against both new coronavirus infection and influenza, while those who did not receive vaccination against these viral infections had bronchial asthma exacerbations due to respiratory infection. Also among patients with bronchial asthma who received influenza vaccination, there were no cases of influenza A and bronchial asthma exacerbations due to respiratory infections. In this regard, influenza vaccination is an important intervention to maintain control of asthma exacerbations. It is noteworthy that no new coronavirus infection was reported among vaccinated adolescents within a year after immunization. At the same time, 6 months after vaccination against a new coronavirus infection, we observed a statistically significant increase in antibody levels in unvaccinated adolescents, indicating the presence of high viral neutralizing activity. Vaccination against novel coronavirus infection in patients with bronchial asthma may be considered a possibility.

Dual Antimicrobial Activity of HTCC and Its Nanoparticles: A Synergistic Approach for Antibacterial and Antiviral Applications Through Combined In Silico and In Vitro Studies

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL).

Inactivation of MS-2 virus in water by rotational generator of hydraulic shock

This study investigates the effect of hydraulic shock waves on inactivation of MS-2 bacteriophage, a norovirus surrogate. A falling circular jet of water spiked with the MS-2 (∼1000 PFU/mL) was repeatedly impacted by a rotating blade, resulting in occurrence of hydraulic shock waves within the liquid region adjacent to the impact. The proof-of-concept rotational generator of hydraulic shock treating 9 L of water spiked with viruses was able to achieve 3 logs reduction of viral plaque count within 80–100 liquid passes at moderate blade impact velocities (namely, 70 and 88 m/s) despite the water temperature not exceeding 40 °C and no detectible cavitation. Within the first 20 liquid passes, most MS-2 capsid proteins were degraded, with their concentration reduced from 22 μg/mL to only 7.3 μg/mL. Due to the lack of further capsid protein destruction, additional reduction in MS-2 plaque count in subsequent 80 passes is indicative of damage inflicted to the viral recognition receptors. All this suggests that shockwaves of moderate amplitude (few tens of MPa) alone are sufficient for effective viral inactivation. Considering this and the device's good scalability potential, rotational hydraulic shock generators could prove effective in treating virus-contaminated waters.

Antiviral Potential of Chiococca alba (L.) Hitchc. Plant Extracts Against Chikungunya and Mayaro Viruses

Chikungunya and Mayaro fevers are viral infectious diseases characterized by fever and arthralgia, for which there are currently no effective vaccines or treatments. The urgent need for novel antiviral agents against Chikungunya virus (CHIKV) and Mayaro virus (MAYV) has led to interest in plant-based compounds that can disrupt the viral replication cycle. Chiococca alba (L.) Hitchc., a Neotropical plant traditionally used by Yucatec Maya healers as an antipyretic and antirheumatic, may hold potential as a source of antiviral agents. This study aimed to evaluate the antiviral potential of C. alba methanolic extracts (CAH21 and CAH24) against CHIKV and MAYV through preliminary in vitro and in silico analyses. The cytotoxicity of two methanolic extracts from C. alba roots was assessed in Vero cells using the neutral red assay, and their viral activity was determined via plaque assay post-treatment. Given the observed antiviral effects, we used computational predictions to explore interactions between the multifunctional nsP2 proteases and secondary metabolites identified in C. alba extracts. The metabolites were identified using high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS). Phytochemical analysis revealed the presence of flavonoids, coumarins, and phenolic acids in the C. alba extracts. In vitro assays demonstrated that both extracts inhibited over 70% of activity against CHIKV and MAYV at a concentration of 60 µg/mL. In silico predictions suggested that the flavonoids naringin and vitexin had the highest affinity for the nsP2 proteases of CHIKV and MAYV, indicating their potential as viral inhibitors. Our findings revealed that C. alba extract represents a promising source of novel antiviral compounds.

Headless hemagglutinin-containing influenza viral particles direct immune responses toward more conserved epitopes.

Seasonal influenza vaccines provide mostly strain-specific protection due to the elicitation of antibody responses focused on evolutionarily plastic antigenic sites in the hemagglutinin head domain. To direct the humoral response toward more conserved epitopes, we generated an influenza virus particle where the full-length hemagglutinin protein was replaced with a membrane-anchored, "headless" variant while retaining the normal complement of other viral structural proteins such as the neuraminidase as well as viral RNAs. We found that a single administration of a headless virus particle-based vaccine elicited high titers of antibodies that recognized more conserved epitopes on the major viral glycoproteins. Furthermore, the vaccine could elicit these responses even in the presence of pre-existing, hemagglutinin (HA) head-focused influenza immunity. Importantly, these antibody responses mediated protective, but non-neutralizing functions such as neuraminidase inhibition and antibody-dependent cellular cytotoxicity. Additionally, we show the vaccine can provide protection from homologous and heterologous challenges in mouse models of severe influenza without any measurable HA head-directed antibody responses. Thus, headless hemagglutinin containing viral particles may represent a tool to drive the types of antibody responses predicted to increase influenza vaccine breadth and durability.IMPORTANCECurrent seasonal influenza vaccines provide incomplete protection from disease. This is partially the result of the antibody response being directed toward parts of the virus that are tolerant of mutations. Redirecting the immune response to more conserved regions of the virus has been a central strategy of next-generation vaccine designs and approaches. Here, we develop and test a vaccine based on a modified influenza virus particle that expresses a partially deleted hemagglutinin protein along with the other viral structural proteins. We demonstrate this vaccine elicits antibodies that recognize the more conserved viral epitopes of the hemagglutinin stalk and neuraminidase protein to facilitate protection against influenza viruses despite a lack of classical viral neutralization activity.

Two amino acid residues in the N-terminal region of the polymerase acidic protein determine the virulence of Eurasian avian-like H1N1 swine influenza viruses in mice.

Reassortant Eurasian avian-like H1N1 (rEA H1N1) viruses carrying the internal genes of H1N1/2009 virus have been circulating in pigs for more than 10 years and have caused sporadic human infections. The enhanced virulence phenotype of the rEA H1N1 viruses highlights potential risks to public health. However, the molecular mechanism underlying the viral pathogenicity of the currently circulating rEA H1N1 viruses remains unclear. In this study, we found that two naturally isolated rEA H1N1 swine influenza viruses, A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), possessed similar genetic characteristics but exhibited significantly different pathogenicity in a mouse model. Using reverse genetics, we demonstrated that amino acid mutations at positions 100 and 122 in the polymerase acidic (PA) protein had individual and synergistic effects on the polymerase activity and viral replication capacity in vitro, as well as the viral pathogenicity in mice. Furthermore, we revealed that amino acid residue 100 in PA influenced the transcription of viral RNA (vRNA) by altering the endonuclease activity, and amino acid residue 122 affected the synthesis of complementary RNA and messenger RNA by altering the RNA-binding ability and endonuclease activity of the PA protein. Taken together, we identified that two naturally occurring amino acid mutations in PA derived from H1N1/2009 virus are crucial determinants of the virulence of rEA H1N1 viruses and revealed the differential mechanism by which these two mutations affect the transcription and replication of vRNA. These findings will extend our understanding of the roles of PA in the virulence of influenza A viruses.IMPORTANCEMultiple genetic determinants are involved in the virulence of influenza A viruses. In this study, we identified two naturally occurring amino acid mutations, located at residues 100 and 122 in the polymerase acidic (PA) protein, which are associated with viral polymerase activity, replication competence, and pathogenicity in mice. In particular, we clarified the specific mechanism by which the two residues play an important role in viral transcription and replication. These findings will help to improve understanding the functions of amino acid residues in the N-terminal region of the PA protein involved in the pathogenicity of influenza A viruses.

Lytic promoter activity during herpes simplex virus latency is dependent on genome location.

Herpes simplex virus 1 (HSV-1) is a significant pathogen that establishes lifelong latent infections with intermittent episodes of resumed disease. In mouse models of HSV infection, sporadic low-level lytic gene expression has been detected during latency in the absence of reactivation events that lead to production of new viruses. This viral activity during latency has been reported using a sensitive Cre-marking model for several lytic gene promoters placed in one location in the HSV-1 genome. Here, we extend these findings in the same model by examining first, the activity of an ectopic lytic gene promoter in several places in the genome and second, whether any promoters might be active in their natural context. We found that Cre expression was detected during latency from ectopic and native promoters, but only in locations near the ends of the unique long genome segment. This location is significant because it is in close proximity to the region from which latency-associated transcripts (LATs) are derived. These results show that native HSV-1 lytic gene promoters can produce protein products during latency, but that this activity is only detectable when they are located close to the LAT locus.IMPORTANCEHSV is a significant human pathogen and the best studied model of mammalian virus latency. Traditionally, the active (lytic) and inactive (latent) phases of infection were considered to be distinct, but the notion of latency being entirely quiescent is evolving due to the detection of some lytic gene expression during latency. Here, we add to this literature by finding that the activity can be found for native lytic gene promoters as well as for constructs placed ectopically in the HSV genome. However, this activity was only detectable when these promoters were located close by a region known to be transcriptionally active during latency. These data have implications for our understanding of HSV gene regulation during latency and the extent to which transcriptionally active regions are insulated from adjacent parts of the viral genome.

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.

Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.

Unveiling the silent information of wastewater-based epidemiology of SARS-CoV-2 at community and sanitary zone levels: experience in Córdoba City, Argentina

ABSTRACT The emergence of COVID-19 in 2020 significantly enhanced the application of wastewater monitoring for detecting SARS-CoV-2 circulation within communities. From October 2021 to October 2022, we collected 406 wastewater samples weekly from the Córdoba Central Pipeline Network (BG-WWTP) and six specific sewer manholes from sanitary zones (SZs). Following WHO guidelines, we processed samples and detected SARS-CoV-2 RNA and variants using real-time PCR. Monitoring at the SZ level allowed for the development of a viral activity flow map, pinpointing key areas of SARS-CoV-2 circulation and tracking its temporal spread and variant evolution. Our findings demonstrate that wastewater-based surveillance acts as a sensitive indicator of viral activity, detecting imminent increases in COVID-19 cases before they become evident in clinical data. This study highlights the effectiveness of targeted wastewater monitoring at both municipal and SZ levels in identifying viral hotspots and assessing community-wide circulation. Importantly, the data shows that environmental wastewater studies provide valuable insights into virus presence, independent of clinical COVID-19 case records, and offer a robust tool for adapting to future public health challenges.

Characterization of the symmetrical benzimidazole twin drug TL1228: the role as viral entry inhibitor for fighting COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reliably one of the largest pandemics the world has suffered in recent years. In the search for non-biological antivirals, special emphasis was placed on drug repurposing to accelerate the clinical implementation of effective drugs.The life cycle of the virus has been extensively investigated and many human targets have been identified, such as the molecular chaperone GRP78, representing a host auxiliary factor for SARS-CoV-2 entry. Here we report the inhibitor capacity of TL1228, a small molecule discovered through an in silico screening approach, which could interfere with the interaction of SARS-CoV-2 and its target cells, blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. TL1228 showed in vitro the ability to reduce significantly both pseudoviral and authentic viral activity even through the reduction of GRP78/ACE2 transcript levels. Importantly, TL1228 acts in modulating expression levels of innate immunity and as inflammation markers.