Herpes Simplex Virus Type Research Articles

Improving Retinoic Acid Efficacy: Lipase-Catalyzed Synthesis of Derivatives with Antiviral Activity.

An efficient enzymatic approach was applied to the synthesis of new derivatives of retinoic acid. Nine derivatives, four of them new compounds, were obtained through lipase-catalysis with excellent yield. In order to find the optimal reaction conditions, the influence of various parameters such as enzyme source, nucleophile : substrate ratio, enzyme : substrate ratio, solvent and temperature was studied. The excellent results obtained by lipase catalysis made the procedure very efficient considering their advantages such as mild reaction conditions and low environmental impact. In addition, several synthesized compounds exhibited lower cytotoxicity than the retinoic acid in Vero cells and a remarkably higher antiviral activity against Herpes simplex virus type 1 (HSV-1) and Herpes simplex virus type 2 (HSV-2).

Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037)

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005. Methods: HIV-uninfected adults received a series of 3 rectal PC-1005 doses—4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 hours. Results: Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were grade 1 or 2; 5 were judged study drug related. Plasma MIV-150 peaked 1–2 h after dosing with a median peak concentrations range of 0.07–0.23 ng/mL and median half-life range of 4.9–7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Rectal tissue MIV-150 peaked 0.5–1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume; median tissue concentrations were BLQ beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 hours of antiviral HPV and HSV effects but no anti-HIV activity. Conclusions: MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as a multipurpose prevention technology candidate. Clinical Trials: NCT03408899.

RVG29-modified oncolytic herpes simplex virus for intracranial tumor treatment

Oncolytic virus therapy for brain tumors has achieved breakthrough progress in clinical applications, yet its potential is severely constrained by the mode of administration-direct intratumoral injection into the cranial cavity. Other administration routes face rapid clearance by neutralizing antibodies and obstacles posed by the blood-brain barrier. Herein, we engineered the oncolytic herpes simplex virus type 2 (OH2) with surface modifications of polyethylene glycol (PEG) and rabies virus glycoprotein 29 (RVG29, a BBB-penetrating peptide from the rabies virus), to form OH2-PEG-RVG. OH2-PEG-RVG could efficiently traversed the blood-brain barrier even in BALB/c mice with pre-existing anti-OH2 antibodies, leading to the accumulation of OH2 in the brain. More importantly, OH2-PEG-RVG maintained blood-brain barrier integrity without causing pathological changes or behavioral abnormalities in mice. Furthermore, OH2-PEG-RVG effectively inhibited brain tumor growth, transforming immunologically "cold" tumors into "hot" tumors, inducing a robust anti-tumor immune response, and prolonging the survival of the mice. These findings underscore the potential of OH2-PEG-RVG as a multifaceted therapeutic strategy for effective brain tumor treatment, offering insights into addressing blood-brain barrier limitations.

The study of the antiviral effect of a soft dosage form

Aim. To study the antiviral activity of a soft medicine with mangiferin against the herpes simplex virus. Materials and methods. The studies used samples of the soft dosage form developed with mangiferin, a xanthone belonging to the class of polyphenols. Mangiferin is a light yellow fine crystalline powder obtained from the leaves of the mango tree (Mangifera indica), (manufacturer Shaanxi, China). The substance contains 98.5 % of mangiferin. The antiviral activity was studied on Vero kidney cells of an African green monkey obtained from the Cell Bank of the Institute of Experimental Pathology, Oncology and Radiobiology named after R. E. Kavetsky of the National Academy of Sciences of Ukraine. The cell cultivation was performed according to standard methods. The cultivation and accumulation of the virus was carried out on Vero cell culture. The infectious titer of the virus was 7.4 log10 TCD 50/ml. The MTT modification analysis was used to study the cell viability. The antiviral activity was studied according to standard methods. The virulicidal activity against HSV-1 was determined by decreasing the cytopathic effect of the virus on cells and the virus titer using the MTT method. Results and discussion. The determination of the direct effect of the test sample on the extracellular herpes virus (virucidal effect) of an undiluted sample and samples in a dilution of 1:2.5 and 1:5 showed their ability to exhibit a significant virucidal effect against HSV-1 regardless of the dilution used and the exposure time with the virus. It was found that the decrease in the titer of the herpes virus was within 1.7-2.2 log10. When studying the ability of the test sample to influence the development of the cytopathic effect of the herpes virus on cells, it was determined that in dilutions (1:20-1:320), the sample inhibited the reproduction of the virus and the development of HSV-1 on Vero cells compared to the control virus. The greatest efficiency was found when using the sample in dilutions of 1:80-1:320; the reduction in the development of the cytopathic effect of the virus on cells was in the range of 59-64 %. When studying the infectious titer of the herpes virus synthesized de novo after the treatment with various dilutions of the test sample, it was shown that the test sample in the dilutions used did not significantly affect the synthesis of the infectious progeny of the virus, the decrease in the viral titer did not exceed 1.1 log10. Cytotoxicity assays showed that in the dilutions of 1:40 or more, the maximum reduction in cell viability was 18 %, indicating low toxicity of the sample. Conclusions. According to the results of the study, the ability of the test sample containing 5 % mangiferin to effectively inactivate the extracellular herpes simplex virus Type 1 and significantly inhibit the development of the cytopathic effect of the virus on cells has been found.

Heparanase 2 Modulation Inhibits HSV-2 Replication by Regulating Heparan Sulfate

The host enzyme heparanase (HPSE) facilitates the release of herpes simplex virus type 2 (HSV-2) from target cells by cleaving the viral attachment receptor heparan sulfate (HS) from infected cell surfaces. HPSE 2, an isoform of HPSE, binds to but does not possess the enzymatic activity needed to cleave cell surface HS. Our study demonstrates that HSV-2 infection significantly elevates HPSE 2 protein levels, impacting two distinct stages of viral replication. We show that higher HPSE 2 negatively affects HSV-2 replication which may be through the regulation of cell surface HS. By acting as a competitive inhibitor of HPSE, HPSE 2 may be interfering with HPSE’s interactions with HS. We demonstrate that the enhanced expression of HPSE 2, either via viral infection or plasmid transfection, reduces HPSE’s ability to cleave HS, thereby hindering viral egress. Conversely, low HPSE 2 levels achieved through siRNA transfection allow HPSE to cleave more HS, reducing viral entry. Altogether, we propose a hypothetical model in which the modulation of HPSE 2 impedes HSV-2 replication by regulating HS availability on the cell surface. This dual role of HPSE 2 in viral replication and potential tumor suppression underscores its significance in cellular processes and viral pathogenesis.

Construction of a stable 4T1 cell line expressing UL19 by the PiggyBac transposon system

To investigate the mechanism of the major capsid protein VP5 (encoded by the UL19 gene) of oncolytic herpes simplex virus type Ⅱ (oHSV2) in regulating the antitumor function of immune cells, we constructed a mouse breast cancer cell line 4T1-iRFP-VP5-GFP stably expressing VP5 protein, near-infrared fluorescent protein (iRFP), and green fluorescent protein (GFP) by using the PiggyBac transposon system. Flow cytometry and Western blotting were employed to screen the monoclonal cell lines expressing both GFP and VP5 and examine the expression stability of UL19 in the constructed cell line. The results of SYBR Green I real-time PCR and Western blotting showed that the copies of UL19 and the expression level of VP5 protein in the 15th passage of 4T1-iRFP-VP5-GFP cells were significantly higher than those in the 4T1 cells transiently transfected with UL19, demonstrating the stable insertion of UL19 into the 4T1 cell genome. The real-time cell analysis (RTCA) was employed to monitor the proliferation of 4T1-iRFP-VP5-GFP cells, which showed similar proliferation activity to their parental 4T1 cells. Further studies confirmed that NK92 cells exhibited stronger cytotoxicity against 4T1-iRFP-VP5-GFP cells than against 4T1 cells. This study layed a foundation for elucidating the role of VP5 protein in regulating immune cells, including T cells and NK cells, via HLA-E in 4T1 cells to exert the anti-tumor function.

Antiviral potential of copper and titanium dioxide nanoparticles against H1N1, Adenovirus 40 and herpes simplex virus type-II

The rising incidence of viral illnesses like influenza (H1N1), human adenovirus (AdV) 40, and herpes simplex virus type 2 (HSV-II) seriously threatens public health, necessitating the development of potent antiviral medications. The main objective of this study was to evaluate the antiviral activity of synthesized copper nanoparticles (Cu-NPs) and titanium dioxide nanoparticles (TiO2-NPs) against the three mentioned viruses. Characterization of these compounds was performed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) and UV–Vis spectroscopy techniques. The cytotoxicity and antiviral activity of viruses were investigated using the crystal violet technique. The main findings reveal that Cu-NPs had significant antiviral activity, especially against HSV-II, with an IC50 value of 20.449 μg/mL. However, this activity may be accompanied by marked cytotoxicity, indicated by a CC50 of 123.492 µg/mL, raising concerns about its safety for therapeutic use and its negative impact on human health. In contrast, TiO2-NPs show a more favorable safety profile, with a CC50 of 264.10 μg/mL, maintaining moderate antiviral activity against H1N1 and HSV-II, albeit with higher IC50 values compared to Cu-NPs. Based on these results, Cu-NPs and TiO2-NPs are both attractive candidates for the creation of new antiviral treatments, and more research into their mechanisms of action and their therapeutic uses is necessary.

Expression of Viral DNA Polymerase in Synthetic Recombinant Adeno-Associated Virus Producer Cell Line Enhances Full Particle Productivity.

Recombinant adeno-associated virus (rAAV) is a widely used viral vector in gene therapy. To meet the growing clinical demand, a scalable production technology which can efficiently produce high-quality products is required. We have developed a synthetic biology strategy to generate HEK293-based cell lines which have integrated essential AAV and adenoviral helper genes and are capable of producing rAAV upon induction. One such cell line, GX6B, produced up to 106 capsids per cell, but only a much lower level of rAAV genomes. The low AAV genome titer limited its rAAV productivity and increased empty viral particle content. To boost AAV genome amplification, the coding sequence of the DNA polymerase complex (UL30/UL42) from helper Herpes Simplex Virus type 1 (HSV-1) was placed under an inducible promoter control and integrated into GX6B genome at a relatively low level. The resulting clones produced significantly higher titer of viral genomes, while their capsid level was unaffected. As a result, the encapsidated rAAV2 titer and the full particle content were significantly increased. We further demonstrated that this strategy of expressing HSV-1 DNA polymerase to increase full particle productivity could be implemented in a synthetic cell line producing another serotype rAAV8.

Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins.

As obligate intracellular pathogens, viruses activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of salvage nicotinamide adenine dinucleotide (NAD+) synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses through unknown mechanisms. Here, we show that NAMPT restricts herpes simplex virus type 1 (HSV-1) replication by impeding the virion incorporation of viral proteins owing to its phosphoribosyl-hydrolase (phosphoribosylase) activity, which is independent of the role of NAMPT in NAD+ synthesis. Proteomics analysis of HSV-1-infected cells identifies phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins, which are de-phosphoribosylated by NAMPT in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Loss of NAMPT renders mice highly susceptible to HSV-1 infection. Our work describes an additional enzymatic activity of a metabolic enzyme in viral infection and host defence, offering a system to interrogate the roles of protein phosphoribosylation in metazoans.

Control of HSV-1 Infection: Directions for the Development of CRISPR/Cas-Based Therapeutics and Diagnostics.

It is estimated that nearly all individuals have been infected with herpesviruses, with herpes simplex virus type 1 (HSV-1) representing the most prevalent virus. In most cases, HSV-1 causes non-life-threatening skin damage in adults. However, in patients with compromised immune systems, it can cause serious diseases, including death. The situation is further complicated by the emergence of strains that are resistant to both traditional and novel antiviral drugs. It is, therefore, imperative that new methods of combating HSV-1 and other herpesviruses be developed without delay. CRISPR/Cas systems may prove an effective means of controlling herpesvirus infections. This review presents the current understanding of the underlying molecular mechanisms of HSV-1 infection and discusses four potential applications of CRISPR/Cas systems in the fight against HSV-1 infections. These include the search for viral and cellular genes that may serve as effective targets, the optimization of anti-HSV-1 activity of CRISPR/Cas systems in vivo, the development of CRISPR/Cas-based HSV-1 diagnostics, and the validation of HSV-1 drug resistance mutations.

A label-free optical biosensor-based point-of-care test for the rapid detection of Monkeypox virus

Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation In our latest work, we have further improved our previous 'Single-Particle' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, 'Pixel-Diversity' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/mL (∼3.3 aM). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface.

Minimally Invasive Transthoracic Intramyocardial Cellular Transplantation Under Echocardiographic Guidance for Myocardial Impairment

Abstract Objective: To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study. Methods: Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) (n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CMTK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CMTK+ in vivo. Cardiac function and morphology were evaluated by echocardiography. Results: The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively (P < 0.01). Conclusion: A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CMTK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.

Non-replicative herpes simplex virus genomic and amplicon vectors for gene therapy - an update.

Two major types of defective vectors have been derived from herpes simplex virus type 1 (HSV-1), non-replicative genomic vectors (nrHSV-1), and amplicon vectors. This review recapitulates the main features of both vector types and summarizes recent improvements in our understanding of virus/vector biology, particularly with regard to the critical role played by the overpowering of antiviral cellular defenses and the epigenetic control of viral gene expression. Over the past years, significant breakthroughs in vector design, genetic engineering, and HSV-1 biology have accelerated the development of nrHSV-1 vectors. The low immunogenicity and enhanced safety profiles allowed the successful translation of these vectors into several clinical trials, with some being approved by the FDA. Regarding amplicons, despite their advantage in carrying very large or multiple transgenes, and their potential to avoid genome dilution in dividing cells, the absence of production procedures capable of generating large amounts of helper-free amplicons at reasonable cost with GMP compliance, still limits the translation of these outstanding vectors to clinical trials.

TMET-30. ONCOLYTIC HSV REWIRES METABOLISM TO PROMOTE ANTITUMOR IMMUNITY THROUGH REDUCTIVE CARBOXYLATION AND FERROPTOSIS

Abstract Cancer cells autonomously rewire metabolism to meet increased bioenergetic demands. Oncolytic HSVs (oHSVs) are attenuated Herpes simplex type 1 derived viruses that lyse tumor cells releasing damage-associated molecules triggering antitumor immunity. Currently one oHSV-1 derived virus is approved for melanoma treatment in the USA and another for recurrent GBM in Japan. While several other viruses are being evaluated in clinical trials for safety and efficacy, an understanding of the impact of oHSV therapy on cancer cell metabolism is largely unexplored. A detailed understanding of how oHSV impact tumor cell metabolism and oxidative stress is important to understand the unique susceptibilities that can further be exploited to improve the therapeutic index. Here, we analyzed transcriptomic changes in tumor biopsies of recurrent high-grade glioma patients treated with oHSV. RNA-seq data obtained from pre- and post-G207 treated biopsies from phase-Ib study patients (NCT00028158) revealed enrichment in pathways related to citric acid cycle, oxidative phosphorylation, and glutamate metabolism. We confirmed these changes by RNA sequencing of oHSV-infected patient derived GBM cells. Mechanistically, oHSV hijacked cellular glucose metabolism to increase oxidative phosphorylation and modulated cellular glutamine metabolism towards reductive carboxylation and reduced free glutathione, collectively contributing to increased ROS generation. Kinome profiling revealed PKC activation upon treatment with oHSV. Increased ROS combined with reduced glutathione, and PKC activation promoted ferroptotic cell death characterized by increased lipid peroxidation and smaller, ruptured mitochondria, and contributed to immunotherapy by this treatment. IDH mutant tumors that block reductive carboxylation were resistant to oHSV-induced ferroptotic cell death and did not benefit from oHSV-induced antitumor benefit. Together, this study presents avenues to enhance antitumor immunity by oHSV therapy.

The loss of both pUL16 and pUL21 in HSV-1 infected cells abolishes cytoplasmic envelopment.

Previously, we had developed synthetic genomics methods to assemble an infectious clone of herpes simplex virus type-1 (HSV-1). To do this, the genome was assembled from 11 separate cloned fragments in yeast using transformation associated recombination. The eleven fragments or "parts" spanned the 152 kb genome and recombination was achieved because of the overlapping homologous sequences between each fragment. To demonstrate the robustness of this genome assembly method for reverse genetics, we engineered different mutations that were located in distant loci on the genome and built a collection of HSV-1 genomes that contained single and different combination of mutations in 5 conserved HSV-1 genes. The five genes: UL7, UL11, UL16, UL21 and UL51 encode virion structural proteins and have varied functions in the infected cell. Each is dispensable for virus replication in cell culture, however, combinatorial analysis of deletions in the five genes revealed "synthetic-lethality" of some of the genetic mutations. Thus, it was discovered that any virus that carried a UL21 mutation in addition to the other gene was unable to replicate in Vero cells. Replication was restored in a complementing cell line that provided pUL21 in trans. One particular combination (UL16-UL21) was of interest because the proteins encoded by these genes are known to physically interact and are constituents of the tegument structure. Furthermore, their roles in HSV-1 infected cells are unclear. Both are dispensable for HSV-1 replication, however, in HSV-2 their mutation results in nuclear retention of assembled capsids. We thus characterized these viruses that carry the single and double mutant. What we discovered is that in cells where both pUL16 and pUL21 are absent, cytoplasmic capsids were evident but did not mature into enveloped particles. The capsid particles isolated from these cells showed significantly lower levels of incorporation of both VP16 and pUL37 when compared to the wild-type capsids. These data now show that of the tegument proteins, like the essential pUL36, pUL37 and VP16; the complex of pUL16 and pUL21 should be considered as important mediators of cytoplasmic maturation of the particle.

Combined effect of basic antiherpetic drugs with a new inhibitor of the terminase complex of herpes simplex virus type 1 in Vero cell culture

More than 90% of the world’s population are carriers of herpes simplex virus type 1 (HSV-1). The infection manifests itself in the formation of blisters and ulcers on the face or genitals, and can cause blindness, encephalitis, and generalized infection. All modern first- and second-line antiherpetic drugs selectively inhibit viral DNA-polymerase. The purine-benzoxazine conjugate LAS-131 [(S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine], which we described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits its reproduction in vitro. For the first time, we have obtained fundamentally new results on the combined effect of LAS-131 on human herpesvirus infection with practically significant antiviral compounds – nucleoside analogues (acyclovir [ACV], penciclovir [PCV], ganciclovir [GCV], brivudine [BVDU], iododeoxyuridine [IDU], adenine arabinoside [Ara-A], as well as a nucleoside phosphonate analogue (cidofovir [CDV]) and a pirophosphate analogue (foscarnet [FOS]). Using a inhibition assay of cytopathic effect (CPE) induced by a virus, it was shown that when combined with LAS-131, the concentrations of the compounds in combinations providing inhibition of HSV-1-induced CPE by 50%, decreased by 2 times (additive effect, FOS) or more (synergistic effect, ACV, PCV, GCV, IDU, BVDU, Ara-A, CDV). Reducing the concentrations of agents creates non-permissive conditions for the reproduction of HSV-1 and opens up new real possibilities for controlling human herpesvirus infection.

Biological activities of Elaeagnus umbellata methanol extract

Elaeagnus umbellata, known as Autumn olive and growing widely in Asia and Southern Europe, is a shrub tree used in the traditional treatment of many diseases, including cancer. In this study, it was aimed to investigate the several biological effects of methanol extract of E. umbellate. The activity of the extract on 11 microorganisms was determined by the agar well diffusion technique. The anti-quorum sensing activity of the extract was tested using Chromobacterium violaceum ATCC 12472. The anti-biofilm and anti-swarming activities were tested using Pseudomonas aeruginosa PAO1. Cytotoxic effect of the extract against pancreatic tumoral cell line (AR42J), breast cancer cell line (MDA-MB-231), lung adenocarcinoma cell line (A549), and normal epithelial cell line (Vero), and antiviral effect of the extract against herpes simplex virus type 1 was analyzed using the MTT method. It was determined that the extract was moderately effective against 6/11 microorganisms and showed anti-quorum sensing activity. While the extract did not have a cytotoxic effect on cancer cell lines, it was found to have a cytotoxic effect on Vero cells at concentrations of 100 µg/mL and above. However, no anti-biofilm, anti-swarming, and antiviral activity of the extract was observed. The study shows that E. umbellata fruit has limited biological activity.

Disseminated herpes simplex virus infection in pregnancy

Herpes simplex virus (HSV) types 1 and 2 produce the most common sexually transmitted infection in women, with a higher incidence reported in developing countries. When the first infection occurs during the perinatal period, it can spread, resulting in high morbidity and mortality of the mother and child, in addition to mainly neurological sequelae in the newborn. Despite having reliable laboratory tests, the diagnosis of herpes simplex virus infection in this population is complex since the clinical presentation ranges from asymptomatic or with non-specific symptoms without lesions on the skin or mucous membranes. For this reason, a high clinical suspicion is necessary. Here, we present the case of a mother with disseminated herpes simplex virus type 2 infection with viral hepatitis and fetal death, highlighting the importance of suspecting the diagnosis in febrile women with systemic compromise during the perinatal period, even in the absence of rash.

TRIM Proteins: Key Regulators of Immunity to Herpesvirus Infection.

Herpesviruses are ubiquitous DNA viruses that can establish latency and cause a range of mild to life-threatening diseases in humans. Upon infection, herpesviruses trigger the activation of several host antiviral defense programs that play critical roles in curbing virus replication and dissemination. Recent work from many groups has integrated our understanding of TRIM (tripartite motif) proteins, a specific group of E3 ligase enzymes, as pivotal orchestrators of mammalian antiviral immunity. In this review, we summarize recent advances in the modulation of innate immune signaling by TRIM proteins during herpesvirus infection, with a focus on the detection of herpes simplex virus type 1 (HSV-1, a prototype herpesvirus) by cGAS-STING, RIG-I-like receptors, and Toll-like receptors. We also review the latest progress in understanding the intricate relationship between herpesvirus replication and TRIM protein-regulated autophagy and apoptosis. Finally, we discuss the maneuvers used by HSV-1 and other herpesviruses to overcome TRIM protein-mediated virus restriction.

Antiviral Potential and Chemical Composition of Wild Baccharis crispa Spreng. Populations (Asteraceae) from Córdoba, Argentina: Perspective on Population Variability.

Medicinal plants have been explored worldwide as potential alternatives for the prevention and treatment of different diseases, including viral infections. Baccharis crispa Spreng. (Asteraceae) is a native medicinal species widely used in South America. Given the influence of genetic and environmental factors on secondary metabolites biosynthesis and accumulation, this study aimed to evaluate the in vitro antiviral activity of four wild populations of B. crispa from Córdoba, Argentina, and assess the variability in their bioactivity and chemical composition. The cytotoxicity of chloroform, ethanol, and aqueous extracts from aerial parts was evaluated by the neutral red uptake method. Antiviral and virucidal activity against herpes simplex virus type 1 (HSV-1) and chikungunya virus (CHIKV) were assessed via plaque-forming unit (PFU) reduction assay. Phytochemical analyses of the extracts were conducted using HPLC-ESI- MS/MS. The Puesto Pedernera population showed the strongest antiviral activity, with inhibition rates of 82% for CHIKV and 79% against HSV-1, as well as potent virucidal effects, reducing PFU formation by up to 5 logarithms for both viruses. Remarkably, ethanol extract exhibited the least toxicity and strongest inhibitory activity. Villa del Parque population was inactive. We identified 38 secondary metabolites, predominantly phenolic acids (12) and flavonoids (18), in varying proportions. Delphinidin and delphinidin-3-glucoside are described for the first time in the species. Differences in phytochemical profiles were observed among extract types and populations. Key phenolic compounds showed moderate positive correlations with the evaluated bioactivities, emphasizing the complexity of phytochemical properties and interactions. These results highlight the therapeutic potential of B. crispa extracts against viral infections and underscore the importance of considering the geographical source of plant material in bioactivity evaluations.