Evaluation of polymer combinations in vaginal mucoadhesive tablets for the extended release of acyclovir.

Genital herpes, caused by herpes simplex virus type 2 (HSV-2), affects nearly 500 million people, mostly women. Since the main route of transmission is sexual contact, the development of an acyclovir extended-release vaginal microbicide would be a suitable tool for the prevention of virus transmission. In this work, we evaluated the potential of three polymers with different characteristics (chitosan, xanthan gum and ethyl cellulose) for obtaining acyclovir extended-release vaginal tablets. By combining the polymers, certain useful synergies were observed to modify their mucoadhesive capacity and control drug release. In the swelling studies, it observed that a polyelectrolyte complex with more moderate swelling and sustained gelation was formed between chitosan and xanthan gum exclusively in acidic medium (simulated vaginal fluid). This complex allowed prolonging the mucoadhesion of the tablets in ex vivo studies performed with vaginal mucosa, which would translate into better retention in the vagina after administration. In addition, the combination of chitosan and xanthan gum allowed obtaining a controlled release of acyclovir for 5 days, regardless of the pH of the medium, which would guarantee that drug release continues even in the presence of seminal fluid.

Quality of Caregiver-Adolescent Relationship on HIV, Herpes Simplex Virus Type-2, and on Pregnancy Among Young Women in South Africa Enrolled in HIV Prevention Trials Network 068.

PURPOSE: Adolescent girls and young women (AGYW) are at an increased risk of acquiring HIV and HSV-2, and unintended pregnancies are high in AGYW. Despite the protective impact of caregiver-adolescent relationships on risk behaviors, less attention has been paid to the association of these relationships and sexually transmitted infections (STIs) and pregnancy. METHODS: We used longitudinal data from HIV Prevention Trial Network 068, which was conducted among 2,533 AGYW (13 - 20 years) over 5 years in Agincourt, South Africa. Kaplan-Meier and Cox models were used to estimate the effect of quality of caregiver-adolescent relationships (caring and closeness) on STIs and pregnancy. Also, we assessed effect measure modification by age (14-19 vs. 20-25 years) for STI risk using stratum-specific estimates and likelihood ratio tests, with a p value <.1 indicative of effect measure modification. RESULTS: There were no significant differences in the hazard of HIV by our exposures (caring: hazard ratio (HR): 1.03, 95% CI: 0.75, 1.42; closeness: HR: 0.80, 95% CI: 0.57, 1.11). Among 14-19-year-olds, those who reported caregiver caring were less likely to acquire HSV-2 (HR: 0.69, 95% CI: 0.51, 0.94, likelihood ratio tests= 3.89, p-value = .0487), in contrast, there were no significant differences among 20 - 25-year-olds. AGYW who reported high-quality relationships had a lower hazard of pregnancy incidence (caring: HR: 0.79, 95% CI: 0.68, 0.93; closeness: HR: 0.76; 95% CI: 0.64, 0.91). DISCUSSION: Positive caregiver-adolescent relationships are associated with reduced risk of HSV-2 among younger AGYW and pregnancy incidence.

Pegaharolines A - I, structurally novel indole alkaloids with anti-HSV-2 virus activities from Peganum harmala L. seeds.

Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A - I (1-9), and 11 known ones (10-20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5-6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1-6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC50 = 0.90 ± 0.10 µM) was much better than that of the positive control (acyclovir, IC50 = 1.12 ± 0.15 µM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products.

Prevalence of sexually transmitted infections (STIs) among first time visitors at STIs clinic in Hangzhou, China: Assessing the influence of the COVID-19 pandemic.

BACKGROUND: This study assesses the prevalence of sexually transmitted infections (STIs) in first time visitors to the STIs clinic in Hangzhou, China, considering different genders, ages and symptoms. And also explores howthe COVID-19 pandemic has affected on STIs. METHODS: From 2019 to 2023, 27,283 first time visitors were tested for nine distinct STIs, including Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV), syphilis, Herpes Simplex Virus type 2 (HSV-2), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and vaginal Candida. RESULTS: Symptomatic male and female visitors showed overall STI-positive rates of 39.27% and 59.20%, respectively(p < .001). The top three pathogens in both genders were HPV (47.56% and 56.71%), UU (29.21% and 56.47%), and HSV-2 (22.41% and 52.94%). Among asymptomatic visitors, the total STI-positive rate was 36.63% in males and 52.03% in females. Age-stratified analysis revealed higher STI rates in visitors ≤ 20 or >50 years, regardless of gender and symptoms. During the COVID-19 pandemic, symptomatic visitors showed lower positive rates for HPV, HIV, syphilis, and HSV-2, while Candida, UU, CT, NG, and multiple infections increased. Among asymptomatic visitors, HPV had the lowest positive rate, while NG and multiple infections increased during the pandemic. CONCLUSION: STI prevalence is notably high, particularly in those aged ≤ 20 and >50 years. It emphasizes the need for enhanced health education, condom use, and vaccination. The COVID-19 pandemic impacting STIs through varied factors, such as reduced sexual activity and clinical service interruption.

Analysis of HSV1/2 Infection Reveals an Association between HSV-2 Reactivation and Pregnancy.

The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males (p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection.

Fas/FasL-Mediated Apoptosis and Inflammation Contribute to Recovery from HSV-2-Mediated Spinal Cord Infection.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that causes a persistent infection in sensory ganglia. The infection manifests itself as genital herpes but in rare cases it can cause meningitis. In this study, we used a murine model of HSV-2 meningitis to show that Fas and FasL are induced within the CNS upon HSV-2 infection, both on resident microglia and astrocytes and on infiltrating monocytes and lymphocytes. Mice lacking Fas or FasL had a more severe disease development with significantly higher morbidity, mortality, and an overall higher CNS viral load. In parallel, these Fas/FasL-deficient mice showed a severely impaired infection-induced CNS inflammatory response with lower levels of infiltrating CD4+ T-cells, lower levels of Th1 cytokines and chemokines, and a shift in the balance between M1 and M2 microglia/monocytes. In vitro, we confirmed that Fas and FasL is required for the induction of leucocyte apoptosis, but also show that the Fas/FasL pathway is required for adequate cytokine and chemokine production by glial cells. In summary, our data show that the Fas/FasL cell death receptor pathway is an important defense mechanism in the spinal cord as it down-regulates HSV-2-induced inflammation while at the same time promoting adequate anti-viral immune responses against infection.

HSV-2 Manipulates Autophagy through Interferon Pathway: A Strategy for Viral Survival.

Autophagy, an evolutionarily conserved cellular process, influences the regulation of viral infections. While the existing understanding indicates that Herpes Simplex Virus type 2 (HSV-2) maintains a basal level of autophagy to support its viral yield, the precise pathways governing the induction of autophagy during HSV-2 infection remain unknown. Therefore, this study aims to explore the role of type I interferons (IFN-I) in modulating autophagy during HSV-2 infection and to decode the associated signaling pathways. Our findings revealed an interplay wherein IFN-I regulates the autophagic response during HSV-2 infection. Additionally, we investigated the cellular pathways modulated during this complex process. Exploring the intricate network of signaling events involved in autophagy induction during HSV-2 infection holds promising therapeutic implications. Identifying these pathways advances our understanding of host-virus interactions and holds the foundation for developing targeted therapeutic strategies against HSV-2. The insight gained from this study provides a platform for exploring potential therapeutic targets to restrict HSV-2 infections, addressing a crucial need in antiviral research.

Helicase-primase inhibitors for the treatment of herpes simplex virus infections - patent evaluation of WO2023/225162 from Gilead Sciences Inc.

Helicase-primase is an interesting target for small-molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors (HPIs). Here, we analyze the first patent application from Gilead in this field, which pursued a me-too approach combining elements from an old Bayer together with a recent Medshine HPI application (which covers the Phaeno Therapeutics drug candidate HN0037). The asset was contributed to Assembly Biosciences, where it is under development as ABI-1179 at the investigational new drug (IND) enabling stage for high-recurrence genital herpes. A structure proposal for indolinoyl derivative ABI-1179 is presented, showing its potential opportunities and limitations compared to other HPIs.

Antiviral Efficacy of Coridothymus capitatus Essential Oil Against HSV-1 and HSV-2.

Coridothymus capitatus is a perennial herb with aromatic leaves and flowers, distinct from Thymus vulgaris in its chemical composition, resulting in a unique Thymus Essential Oil (TEO). A main component of TEO, carvacrol, is known for its antimicrobial and insecticidal activity. Carvacrol has potent antibacterial, antioxidant, anti-inflammatory, and antifungal properties, generating interest in traditional medicine. However, studies on its antiviral activity are limited. Given the rise in viral infections and limitations of synthetic antiviral drugs, natural antiviral agents are promising due to their efficacy, lower resistance development, and reduced side effects. This study assessed the antiviral efficacy of TEO compared to that of pure carvacrol. We tested various viruses, revealing significant inhibitory effects of TEO on the replication of only Simplexvirus humanalpha1 (HSV-1) and Simplexvirus humanalpha2 (HSV-2), with specific interference during the early stages of the viral replication cycle after the adsorption period. TEO exhibited inhibitory effects at doses below the cytotoxic threshold, with IC50 values of 47 µg/mL for HSV-1 and 40 µg/mL for HSV-2. Maximum virus inhibition was achieved when TEO was added within 90 min post-infection, indicating interference with early viral replication steps. These findings highlight the potential of TEO as a natural antiviral agent and suggest further research into its mechanisms and clinical applications.

Targeting Peptidylarginine Deiminase 3 to Efficiently Suppress Herpes Simplex Virus Type 2 Infection.

Protein expression is regulated through multiple mechanisms, including post-translational modifications (PTMs), which can alter protein structure, stability, localization, and function. Among these, citrullination stands out due to its ability to convert arginine residues into citrulline, altering protein charge and mass. This modification is catalyzed by calcium-dependent protein arginine deiminases (PADs), enzymes implicated in various inflammatory diseases. We have recently shown that human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) exploit these enzymes to enhance their replication capabilities. Although the role of PADs in HCMV and HSV-1 infections is well documented, their involvement in HSV-2 infection has not yet been thoroughly investigated. Here, we demonstrate that HSV-2 manipulates the overall protein citrullination profile by activating three PAD isoforms: PAD2, PAD3, and PAD4. However, as previously observed during HSV-1 infection, PAD3 is the most significantly upregulated isoform, both at the mRNA and protein levels. Consistently, we demonstrate that inhibiting PAD3, either through the specific inhibitor CAY10727 or via CRISPR/Cas9-mediated gene silencing, markedly reduces HSV-2 replication and viral protein expression. Lastly, we show that CAY10727 displays an IC50 value of 0.3 µM, which is extremely close to what was previously observed for HSV-1. Overall, our findings highlight the crucial role of PAD3 in the life cycle of HSV-2 and suggest that the targeted inhibition of PAD3 may represent a promising approach for treating HSV-2 infections, especially in cases resistant to existing antiviral therapies.

Comparison of the Accuracy of HSV1 and HSV2 Antibody Tests with PCR in the Diagnosis of Recurrent Genital Herpes.

Objective: To assess the accuracy of HSV1and HSV2 antibody testing in identifying genital herpes infection. Methods: A cohort of 299 patients previously diagnosed with recurrent genital herpes, confirmed via PCR, were tested using ELISA for HSV1 and HSV2 IgM and IgG antibodies. The study compared the accuracy of HSV1 and HSV2 antibody tests in diagnosing genital herpes. Results: Among 299 patients, 14 tested positives for HSV1 DNA. Of these, 9 had HSV1 IgG antibodies, but none had HSV2 IgG antibody. Among 278 patients with HSV2 DNA, 149 had HSV1 IgG, 9 had HSV2 IgG, and 97 had both. Seven patients had both HSV1 and HSV2 DNA; 3 had HSV1 IgG, 1 had HSV2 IgG, and 3 had both. The accuracy of HSV1 IgG for HSV1 infection was 64.2%, and for HSV1 and HSV2 co-infection, 85.7%. The accuracy of HSV2 IgG for HSV2 infection was 38.1%, and for HSV1 and HSV2 co-infection, 57.1%. The combined antibody positivity accuracy was 34.9%. Conclusion: Genital herpes is primarily caused by HSV2 (92.98%). A smaller percentage is HSV1 (4.67%) or co-infection (2.34%). Despite relatively low diagnostic accuracy (34.9-85.7%) for antibody detection, combined antibody testing is necessary. Herpes DNA testing is recommended for accurate diagnosis. Absence of antibodies does not rule out genital herpes and clinical assessment is essential.

Disparities in burden of herpes simplex virus type 2 in China: systematic review, meta-analyses, and meta-regressions.

Background: The rising prevalence of herpes simplex type 2 (HSV-2) infection poses a growing global public health challenge. A comprehensive understanding of its epidemiology and burden disparities in China is crucial for informing targeted and effective intervention strategies in the future. Methods: We followed Cochrane and PRISMA guidelines for a systematic review and included publications published in Chinese and English bibliographic systems until March 31st, 2024. We synthesized HSV-2 seroprevalence data across different population types. We used random-effects models for meta-analyses and conducted meta-regression to assess the association between population characteristics and seroprevalence. Results: Overall, 23,999 articles were identified, and 402 publications (1,203,362 participants) that reported the overall seroprevalence rates (858 stratified measures) were included. Pooled HSV-2 seroprevalence among the general population (lower risk) was 7.7% (95% CI: 6.8-8.7%). Compared to the general population, there is a higher risk of HSV-2 prevalence among intermediate-risk populations (14.8%, 95% CI: 11.0-19.1%), and key populations (31.7%, 95% CI: 27.4-36.1%). Female sexual workers (FSWs) have the highest HSV-2 risk (ARR:1.69, 95% CI: 1.61-1.78). We found northeastern regions had a higher HSV-2 seroprevalence than other regions (17.0%, 95% CI: 4.3-35.6%, ARR: 1.38, 95% CI: 1.26-1.50, Northern China as the reference group). This highlighted the disparity by population risk levels and regions. We also found lower HSV-2 prevalence estimates in publications in Chinese bibliographic databases than those in English databases among key populations (such as MSM and HIV-discordant populations). Conclusion: There is a gradient increase in HSV-2 prevalence risk stratification. We also identified region, population, and age disparities and heterogeneities by publication language in the HSV-2 burden. This study provides guidance for future HSV-2 prevention to eliminate disparities of HSV-2 infection and reduce overall HSV-2 burden. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=408108, identifier CRD42023408108.

Local Power: The Role of Tissue-Resident Immunity in Human Genital Herpes Simplex Virus Reactivation.

From established latency, human herpes virus type 2 (HSV-2) frequently reactivates into the genital tract, resulting in symptomatic ulcers or subclinical shedding. Tissue-resident memory (TRM) CD8+ T cells that accumulate and persist in the genital skin at the local site of recrudescence are the "first responders" to viral reactivation, performing immunosurveillance and containment and aborting the ability of the virus to induce clinical lesions. This review describes the unique spatiotemporal characteristics, transcriptional signatures, and noncatalytic effector functions of TRM CD8+ T cells in the tissue context of human HSV-2 infection. We highlight recent insights into the intricate overlaps between intrinsic resistance, innate defense, and adaptive immunity in the tissue microenvironment and discuss how rapid virus-host dynamics at the skin and mucosal level influence clinical outcomes of genital herpes diseases.

Elsberg Syndrome: A Case Report of a Novel Radiographic Presentation.

Introduction: Elsberg syndrome (ES) presents with bowel and bladder dysfunction, resembling cauda equina syndrome, and is classified as a clinicoradiographic syndrome most commonly associated with HSV-2 reactivation. Most cases reveal smooth and continuous nerve enhancement on imaging. Case Description: We present a unique case of ES that presented as several nodular, ring enhancing soft tissue masses along the cauda equina. An 81-year-old woman presented with several weeks of sacral sensory impairment. MRI of the lumbar spine at presentation showed several nodular, ring enhancing soft tissue masses within the thecal sac along the cauda equina, concerning for leptomeningeal carcinomatosis from an unknown primary source. Cerebrospinal fluid (CSF) analysis was notable for lymphocyte predominant pleocytosis and protein elevation, which was nonspecific but suggestive of leptomeningeal carcinomatosis. CSF rapid meningitis panel was positive for HSV2 which was confirmed on HSV2 PCR. The patient was briefly on on acyclovir and was stopped due to lack of meningioencephalitis symptoms. Malignancy workup with cytological analysis and systemic imaging were negative. Given the absence of malignancy and positive HSV2 PCR, the patient was diagnosed with HSV-2 sacral radiculitis and subsequently treated with a full course of intravenous acyclovir with gradual clinical and radiographic improvement. Discussion: Ring-enhancing lesions along the cauda equina are most suggestive of LC. Our case highlights an as of yet unreported presentation of ES which may be valuable for neurologists to be aware of as to avoid any potential diagnostic dilemma, minimize unnecessary and costly testing, and not delay effective treatment.

The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Alzheimer's disease and herpes viruses: Current events and perspectives.

Alzheimer's disease (AD) is a real and current scientific and societal challenge. Alzheimer's disease is characterised by a neurodegenerative neuroinflammatory process, but the etiopathogenetic mechanisms are still unclear. The possible infectious aetiology and potential involvement of Herpes viruses as triggers for the formation of extracellular deposits of amyloid beta (Aß) peptide (amyloid plaques) and intraneuronal aggregates of hyperphosphorylated and misfold could be a possible explanation. In fact, the possible genetic interference of Herpes viruses with the genome of the host neuronal cell or the stimulation of the infection to a continuous immune response with a consequent chronic inflammation could constitute those mechanisms underlying the development of AD, with possible implications in the understanding and management of the disease. Herpes viruses could be significantly involved in the pathogenesis of AD and in particular, their ability to reactivate in particular conditions such as immunocompromise and immunosenescence, could explain the neurological damage characteristic of AD. Our review aims to evaluate the state of the art of knowledge and perspectives regarding the potential relationship between Herpes viruses and AD, in order to be able to identify the possible etiopathogenetic mechanisms and the possible therapeutic implications.

Viral genomic variation and the severity of genital HSV-2 infection as quantified by shedding rate: a viral genome-wide association study.

BACKGROUND: The clinical severity of genital HSV-2 infection varies widely among infected persons with some experiencing frequent genital lesions while others are asymptomatic. The viral genital shedding rate is closely associated with and has been established as a surrogate marker of clinical severity. METHODS: To assess the relationship between viral genetics and shedding, we assembled a set of 145 persons who had the severity of their genital herpes quantified through determination of their HSV genital shedding rate. An HSV-2 sample from each person was sequenced and biallelic variants among these genomes were identified. RESULTS: We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study (vGWAS) identified the minor alleles of three individual unlinked variants as significantly associated with higher shedding rate (p<8.4x10-5): C44973T (A512T), a non-synonymous variant in UL22 (glycoprotein H); A74534G, a synonymous variant in UL36 (large tegument protein); and T119283C, an intergenic variant. We also found an association between the total number of minor alleles for the significant variants and shedding rate (p=6.6x10-7). CONCLUSIONS: These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.

Performance characteristics of highly automated HSV-1 and HSV-2 IgG testing.

Herpes simplex virus (HSV) infections are one of the most common and stigmatized infections of humankind, affecting more than 4 billion people around the world and more than 100 million Americans. Yet, most people do not know their infection status, and antibody testing is not recommended, partly due to poor test performance. Here, we compared the test performance of the Roche Elecsys HSV-1 IgG and HSV-2 IgG, DiaSorin LIAISON HSV-1/2 IgG, and Bio-Rad BioPlex 2200 HSV-1 and HSV-2 IgG assays with the gold-standard HSV western blot in 1,994 persons, including 1,017 persons with PCR or culture-confirmed HSV-1 and/or HSV-2 infection. Across all samples, the Bio-Rad and Roche assays had similar performance metrics with low sensitivity (<85%) but high specificity (>97%) for detecting HSV-1 IgG and both high sensitivity (>97%) and high specificity (>98%) for detecting HSV-2 IgG. The DiaSorin assay had a higher sensitivity (92.1%) but much lower specificity (88.7%) for detecting HSV-1 IgG and comparatively poor sensitivity (94.5%) and specificity (94.2%) for detecting HSV-2 IgG. The DiaSorin assay performed poorly at low-positive index values with 60.9% of DiaSorin HSV-1 results and 20.8% of DiaSorin HSV-2 results with positive index values <3.0 yielding false positive results. Based on an estimated HSV-2 seroprevalence of 12% in the United States, positive predictive values for HSV-2 IgG were 96.1% for Roche, 87.4% for Bio-Rad, and 69.0% for DiaSorin, meaning nearly one of every three positive DiaSorin HSV-2 IgG results would be falsely positive. Further development in HSV antibody diagnostics is needed to provide appropriate patient care.IMPORTANCESerological screening for HSV infections is currently not recommended in part due to the poor performance metrics of widely used commercial HSV-1 and HSV-2 IgG assays. Here, we compare three Food and Drug Administration (FDA)-cleared automated HSV-1 and HSV-2 IgG assays to the gold-standard western blot across nearly 2,000 samples. We find that not all commercially available HSV assays are created equal, with comparably low sensitivities for HSV-1 IgG across platforms and high false positivity rates for DiaSorin on HSV-2 IgG. This study is the first large-scale comparison of performance metrics for the Bio-Rad and Roche assays in over 10 years. Our study confirms that there remains room for improvement in HSV serological diagnostic testing-especially in regard to low sensitivities for HSV-1 IgG detection-and highlights that some previously less-studied assays may have better performance metrics than previously considered typical of commercially available HSV-2 IgG assays.

Replacement of sulfonamide by sulfoximine within a helicase-primase inhibitor with restricted flexibility.

Helicase-primase is an interesting target for the therapy of herpes simplex virus (HSV) infections. Since amenamevir is already approved for varicella-zoster virus (VZV) and HSV in Japan and pritelivir has received breakthrough therapy status for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in me-too approaches. Here, we describe the attempt to improve nervous tissue penetration in Phaeno Therapeutics drug candidate HN0037 to target the latent reservoir of HSV by installing less polar moieties, mainly a difluorophenyl instead of a pyridyl group, and replacing the primary sulfonamide with a methyl sulfoximine moiety. However, all obtained stereoisomers exhibited a weaker inhibitory activity on HSV-1 and HSV-2.

Acute-Onset Lower Extremity Weakness and Urinary Retention in a Chronically Immunosuppressed Patient: Diagnosis and Management of Herpes Simplex Virus Type 2 Myelitis.

A 34-year-old immunosuppressed male presented with worsening bilateral lower extremity weakness and urinary retention accompanied by a painless clean-based chancre on his glans penis. Physical examination revealed symmetrically diminished lower extremity weakness most pronounced with hip flexion and knee extension and absent Achilles reflexes. Full MRI spine without contrast was noncontributory. Lumbar puncture showed elevated protein and total nucleated cells with lymphocytic predominance. Both CSF and serum polymerase chain reaction were positive for herpes simplex virus type 2. He received IV methylprednisolone and acyclovir and underwent four months of physical therapy with complete resolution of his neurologic deficits.