Herpes Simplex Virus Infection Research Articles

Biologics Versus JAK Inhibitors. Part II: Risk of Infections. A Narrative Review.

The risk of infections associated with biological drugs (BD) and Janus kinase inhibitors (JAKi) has been extensively explored in the literature. However, there is a dearth of studies that evaluate both pharmacological groups together and, furthermore, compare them. Here, we review the risk of infections associated with BD and JAKi used in dermatology. A narrative review was performed. All relevant articles evaluating the risk of infection and opportunistic infections with BD and JAKi between January 2010 and February 2024 were selected. Overall, the incidence of infections, serious infections, and opportunistic infections associated with BD and JAKi is low, but higher than in the general population. JAKi approved for dermatological disorders (abrocitinib, baricitinib, deucravacitinib, upadacitinib, ritlecitinib, and topical ruxolitinib) have been shown to be safe, and present a low rate of infections. We found an elevated risk, especially with anti-tumor necrosis factor (anti-TNF) agents, rituximab, and JAKi (particularly tofacitinib at high doses). Specific associations with infections include tuberculosis and tuberculosis reactivation with anti-TNF agents and tocilizumab; candidiasis with anti-interleukin (IL) 17 agents; hepatitisB virus reactivation with rituximab, anti-TNF, and JAKi; and herpes simplex and herpes zoster infections with JAKi (especially tofacitinib and upadacitinib at high doses). The incidence of infections with ustekinumab and anti-IL-23 was very low. Anti-IL-1, nemolizumab, tralokinumab, and omalizumab were not associated with an increased risk of infections. Dupilumab could decrease the incidence of cutaneous infections. Anti-TNF agents, rituximab, and JAKi (particularly tofacitinib) can increase the risk of infections. Close monitoring of patients undergoing these therapies is recommended. Prospective studies with long-term follow-up are needed to comparatively evaluate the risks of infection deriving from treatment with BD and JAKi.

Enantioselective Synthesis of β-l-5-[(E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) Uracil)] (l-BHDU) via Chiral Pure l-Dioxolane.

β-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil (l-BHDU, 17) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l-BHDU (17) has demonstrated excellent anti-VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM-l-BHDU-MP, 24) demonstrated an enhanced pharmacokinetic and antiviral profile. POM-l-BHDU-MP (24), in vivo, effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM-l-BHDU-MP (24) is needed. In this article, an efficient approach for the synthesis of l-BHDU (17) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l- & d-dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l-dioxolane 10 provides enantiomerically pure l-dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l-BHDU (17) and its monophosphate ester prodrug (POM-l-BHDU-MP, 24). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l- & d-dioxolane, which offers avenues for the development and structure-activity relationship studies of l- & d-dioxolane-derived nucleosides.

Estimated global and regional economic burden of genital herpes simplex virus infection among 15–49 year-olds in 2016

BackgroundGlobally, herpes simplex virus (HSV)-2 and -1 infections contribute to a large disease burden, but their full economic consequences remain unclear. This study aims to estimate the global economic impact of genital HSV-2 and HSV-1 infection and its consequences for people with genital ulcer disease, neonatal herpes, and human immunodeficiency virus (HIV) infection attributable to HSV-2.MethodsUsing a societal perspective, the economic burden was calculated at the country level and presented by World Health Organization (WHO) regions and World-Bank income levels. The disease burden was obtained from previously published global disease burden studies in 2016 and disaggregated for 194 countries. Estimates of healthcare resource utilisation were sourced from a literature review, and online interviews were conducted with 20 experts from all 6 WHO regions. Relevant costs were obtained from the literature and estimated in 2016 international dollars (I$).ResultsBoth genital HSV-2 (I$31·2 billion) and HSV-1 (I$4·0 billion) infections and their consequences were estimated to cost I$35·3 billion globally in 2016. The major economic burden was from the Americas and Western Pacific regions combined, accounting for almost two-thirds of the global burden (I$20·8 billion). High- and upper-middle-income countries bore a large proportion of the economic burden (76·6% or I$27·0 billion). Costs were driven by the large number of HSV-2 recurrences; however, even assuming conservatively that people with symptomatic herpes have on average only one episode a year, global costs were estimated at I$16·5 billion.ConclusionsThe global costs of genital HSV infection and its consequences are substantial. HSV prevention interventions have the potential to avert a large economic burden in addition to disease burden; thus, efforts to accelerate HSV vaccine development are crucial.

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009-2014.

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009-2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV-1, and HSV-2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26-1.70; OR 1.09, 95% CI 1.05-1.13; OR 1.06, 95% CI 1.01 - 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29-1.77; OR 1.08, 95% CI 1.04-1.12; OR 1.05, 95% CI 1.01-1.10, respectively) after adjusting all relevant co-factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV-1 infection, while the relationship between HSV-2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years.

A case of chronic ulcerative herpes simplex virus infection in a patient with bullous pemphigoid

A case of chronic ulcerative herpes simplex virus infection in a patient with bullous pemphigoid

Serological status for Toxoplasma gondii and cytomegalovirus in pregnant women

Background and objective. Toxoplasma gondii and CMV cause congenital defects in TORCH (Toxoplasmosis, Rubella virus, cytomegalovirus, and Herpes simplex virus) infections. The primary objective of the study was to estimate the seroprevalence of Toxoplasma gondii (TOXO) and cytomegalovirus (CMV) infections among pregnant women in Al Qurnah, Iraq, and identify the presence of specific Immunoglobulin M (IgM) antibodies indicating recent infections. Material and method. The study tested 1000 healthy pregnant women using VIDAS® TOXO and CMV IgM kits. Results. The findings revealed a significant seroprevalence, with 37.2% of samples positive for Toxoplasma IgM, 22.8% for CMV IgM, and 9.6% for mixed infections. The highest rate of abortions occurred in the first trimester, with a significant increase in abortion parameters among pregnant women infected with T. gondii and CMV. Our study comprised 372 pregnant women with Toxoplasma infection; 286 (76.9%) were rural and 86 (23.1%) urban. Our analysis identified CMV in 228 pregnant women, 159 rural (69.7%), and 69 urban (30.3%). Conclusion. The study suggests a higher prevalence of Toxoplasma IgM compared to CMV IgM infections in the region, emphasizing the importance of early detection and prevention, especially during the first trimester. The results also highlight the need for routine antenatal screening and educational measures to reduce the impact of these infections on pregnancy outcomes.

PA08 Extensive congenital epidermal skin loss with sparing of the palms, soles and head: strikingly similar appearances in four patients with neonatal herpes simplex infection

PA08 Extensive congenital epidermal skin loss with sparing of the palms, soles and head: strikingly similar appearances in four patients with neonatal herpes simplex infection

Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units.

Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis. We performed a multicenter cohort study of infants in neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2020. We included all infants who received acyclovir with complete dosing information. Our primary outcome was the proportion of courses with dosing within 80%-120% of the PopPK recommended daily dose and at the recommended dosing frequency. We compared dosing before and after the publication of the 2014 PopPK recommendations using linear probability modeling. We identified 6862 infants with complete dosing information across 308 centers. Dosing met PopPK recommendations for 41% of treatment courses for infants <30 weeks postmenstrual age (PMA), 71% for infants 30 to <36 weeks PMA and <1% for infants ≥ 36 weeks PMA. Comparison of dosing from 1997 to 2013 with that from 2015 to 2020 showed a significant increase in dosing meeting PopPK recommendations for infants <30 weeks PMA (P = 0.008) and infants 30 to <36 weeks PMA (P = 0.02) but not infants ≥ 36 weeks PMA (P = 0.29). No significant increase in dosing meeting PopPK recommendations was seen for any PMA group when comparison was limited to more recent years (2008-2013 vs. 2015-2020). Dosing meeting PopPK recommendations increased over time for some PMA groups, but dosing different than PopPK recommendations remains common. More research is needed to clarify optimal dosing strategies in these infants.

Management of Pustules and Vesicles in Afebrile Infants ≤60 Days Evaluated by Dermatology.

To assess the management and outcomes of afebrile infants who received a pediatric dermatology consultation for pustules and/or vesicles. Medical records were reviewed for all infants 60 days of age or younger who received a pediatric dermatology consult across 6 academic institutions between September 1, 2013 and August 31, 2019 to identify those infants with pustules and/or vesicles. Of the 879 consults, 183 afebrile infants presented with pustules and/or vesicles. No cerebrospinal fluid cultures or blood cultures were positive for bacteria. No concordant positive urine cultures were identified in infants with cutaneous infection. Nine infants were diagnosed with herpes simplex virus (HSV). Five preterm infants were diagnosed with angioinvasive fungal infections. No serious bacterial infections attributable to a skin source were identified, yet 53% of these infants received parenteral antibiotics. HSV was diagnosed in 7% of this cohort, 77.8% (7/9) of whom were term infants and 22.2% (2 of 9) of whom were preterm. Angioinvasive fungal infection was diagnosed in 3%, all of whom (100%, 5 of 5) were extremely preterm at <28 weeks gestational age. These findings suggest that in full-term afebrile infants ≤60 days, the likelihood of a life-threatening etiology of isolated pustules or vesicles is low once HSV infection is excluded. In preterm infants with pustules and/or vesicles, a high index of suspicion must be maintained, and broad infectious evaluation is recommended. HSV testing is recommended for all infants with vesicles, grouped pustules and/or punched-out erosions.

Flexible nano-liposomes-encapsulated recombinant UL8-siRNA (r/si-UL8) based on bioengineering strategy inhibits herpes simplex virus-1 infection

Herpes simplex virus-1 (HSV-1) infection can cause various diseases and the current therapeutics have limited efficacy. Small interfering RNA (siRNA) therapeutics are a promising approach against infectious diseases by targeting the viral mRNAs directly. Recently, we employed a novel tRNA scaffold to produce recombinant siRNA agents with few natural posttranscriptional modifications. In this study, we aimed to develop a specific prodrug against HSV-1 infection based on siRNA therapeutics by bioengineering technology. We screened and found that UL8 of the HSV-1 genome was an ideal antiviral target based on RNAi. Next, we used a novel bio-engineering approach to manufacture recombinant UL8-siRNA (r/si-UL8) in Escherichia coli with high purity and activity. The r/si-UL8 was selectively processed to mature si-UL8 and significantly reduced the number of infectious virions in human cells. r/si-UL8 delivered by flexible nano-liposomes significantly decreased the viral load in the skin and improved the survival rate in the preventive mouse zosteriform model. Furthermore, r/si-UL8 also effectively inhibited HSV-1 infection in a 3D human epidermal skin model. Taken together, our results highlight that the novel siRNA bioengineering technology is a unique addition to the conventional approach for siRNA therapeutics and r/si-UL8 may be a promising prodrug for curing HSV-1 infection.

Late-Onset Concurrent Infection of Vaccine Strain VZV and HSV-1 after Varicella Vaccination in a Child with Natural killer T Cell Deficiency

AbstractWe describe a case with natural killer cell deficiency of late-onset Oka vaccine varicella zoster virus (VZV) strain and Herpes simplex virus-1 (HSV-1) dual infection resulting in fatal clinical course. An 18-month-old boy presented with a papulovesicular rash, mucocutaneous candidiasis, encephalopathy, and severe respiratory distress 6 months after receiving varicella vaccine. VZV and HSV-1 were analysed by real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) and Oka vaccine strain of VZV by gene sequencing. HSV-1 and VZV dual infection was detected in the blood and skin samples by RT-qPCR. Gene sequencing of VZV isolated from vesicular lesions was compatible with the Oka vaccine strain. Flow cytometry revealed a natural killer deficiency, but whole exome analysis failed to identify an associated genetic defect. Vesicular rashes in immunocompromised patients who were inadvertently vaccinated should be taken seriously, and antiviral therapy should be prompt and aggressive.

A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome.

Guard proteins initiate defense mechanisms upon sensing pathogen-encoded virulence factors. Successful viral pathogens likely inhibit guard protein activity, but these interactions have been largely undefined. Here, we demonstrate that the human pathogen herpes simplex virus 1 (HSV-1) stimulates and inhibits an antiviral pathway initiated by NLRP1, a guard protein that induces inflammasome formation and pyroptotic cell death when activated. Notably, HSV-1 infection of human keratinocytes promotes posttranslational modifications to NLRP1, consistent with MAPK-dependent NLRP1 activation, but does not result in downstream inflammasome formation. We identify infected cell protein 0 (ICP0) as the critical HSV-1 protein that is necessary and sufficient for inhibition of the NLRP1 pathway. Mechanistically, ICP0's cytoplasmic localization and function as an E3 ubiquitin ligase prevents proteasomal degradation of the auto-inhibitory NT-NLRP1 fragment, thereby preventing inflammasome formation. Further, we demonstrate that inhibiting this inflammasome is important for promoting HSV-1 replication. Thus, we have established a mechanism by which HSV-1 overcomes a guard-mediated antiviral defense strategy in humans.

Viral Infection in Upper Gastrointestinal Tract

Viral infections of the upper gastrointestinal (GI) tract are not uncommon in clinical practice; however, these are frequently observed in immunocompromised patients and rarely in immunocompetent hosts. Compared with esophagitis, which may be associated with clinically significant outcomes, the stomach is a relatively rare site for opportunistic infections in immunocompetent patients. The most common clinically relevant upper GI tract viral infections include cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus infections. CMV esophagitis and gastritis, which primarily occur in immunocompromised patients, necessitate antiviral treatment, whereas immunocompetent patients typically respond to proton pump inhibitor administration. Most EBV-induced gastric infections are asymptomatic. However, EBV infection is a known etiological contributor to stomach cancer. EBV-associated gastric cancer shows distinctive clinical, pathological, genetic, and post-genetic mutation features and is therefore a clinically significant entity. Herpetic esophagitis usually affects immunocompromised patients and is uncommon in immunocompetent individuals. In this review, we discuss the general aspects and recent studies that have reported esophageal and gastric infections in immunocompromised patients.

Acyclovir extravasation in a newborn: a case report

ObjectiveExtravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation.Case reportA female newborn (Iranian, Asian) with gestational age 37+2 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women’s Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase.ConclusionEarly diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.

A simple method for the determination of acyclovir concentrations in human plasma using high-performance liquid chromatography

BackgroundAcyclovir is an anti-viral medication given to treat herpes simplex and herpes zoster infection. In some severe conditions such as herpes encephalitis, acyclovir is administered intravenously. However, high acyclovir doses may cause acute kidney injury and low acyclovir dose may predispose the patient to inadequate exposure to acyclovir which could be fatal in some conditions. In such cases, the acyclovir plasma concentrations will potentially guide the diagnosis and management of the kidney injury. In this study, we provide a simple and time-efficient method for analyzing acyclovir in human plasma using high-performance liquid chromatography (HPLC).ResultsThe process starts with a single protein precipitation step by adding acetonitrile to deproteinize 300 µL of plasma. The chromatographic separation conditions consist of a mobile phase of water: methanol (97:3, v/v), a flow rate of 1 mL/min, a run time of 17 min, and a detection wavelength of 254 nm. The calibration curve was linear over the range of (0.70–60 mg/L) (r2 ˃ 0.99). The retention times of acyclovir and the internal standard were around 15 and 12 min, respectively. The intra-day and inter-day analysis of acyclovir in plasma using this method exhibited accuracy and precision of less than 7%, which lies within the acceptable range. Different greenness assessment tools confirmed that the proposed method is eco-friendly.ConclusionThe proposed method of analysis of acyclovir in the plasma using HPLC is simple, green and accurate method. This method could be applied in clinical settings where monitoring acyclovir concentrations is essential as it has wide range of the concentrations that could be detected.

Herpes Simplex Virus-1 Complicated by Postherpetic Neuralgia: A Case Report

BACKGROUND: The following case describes management of severe persistent vulvar pain from postherpetic neuralgia through a ganglion impar block. CASE REPORT: A 21-year-old female patient initially presented with genital lesions consistent with herpes simplex virus-1 (HSV-1) and antibody testing suggestive of primary HSV-1 infection. After her genital lesions resolved, she continued to have severe persistent vulvar pain and was diagnosed with postherpetic neuralgia, approximately one year after initial presentation. After unsuccessful medical management with her gynecologist and primary care physician, she was referred to a specialty pain management clinic, where a ganglion impar block was performed and provided significant pain relief. CONCLUSIONS: Genital HSV-1 is a rare cause of postherpetic neuralgia which can cause debilitating pain. Its management requires a multidisciplinary approach, including gynecology, pain management, physiatry, and if appropriate, behavioral health. KEY WORDS: Vulvar pain, postherpetic neuralgia, ganglion impar block, genital pain, case report

Management of Genital Herpes Simplex Virus Infection for the Pregnant Woman

Given the prevalence of genital herpes simplex virus infection in childbearing women and the serious consequences of genital herpes transmission to the newborn during delivery, optimal management of genital herpes during pregnancy is justified. Prevention and health promotion, continuity of care and the participation of the woman and her partner in care are key elements for optimal management of the pregnant woman with genital herpes. Appropriate management of serodiscordant couples must include screening tests for the pregnant woman with a partner who is a HSV-2 carrier, proven diagnosis and individualized prenatal preventive measures. Optimising preventive measures should bring about a reduction of genital lesions at the time of delivery and consequently reduce the number of cases of neonatal herpes and of transfers of care from midwife to physician.

Stability Indicating Method Development and Validation for Estimation of Valacyclovir in Pharmaceutical Preparation

Valacyclovir is an antiviral drug that is frequently administered to treat herpes simplex and herpes zoster infections. A simple, rapid, and accurate method for quantifying valacyclovir hydrochloride in tablet and bulk form has been developed. Two distinct analysis approaches, UV and HPLC, were developed in the present study for the evaluation of valacyclovir hydrochloride in pharmaceutical preparation. The mobile phase employed in the UV technique was Methanol:10mM KH2PO4 Buffer (50:50) for estimation of the drug at 254nm, and the (VAL) achieved was 99.45%. The method's validation was completed in accordance with ICH Q2 R1 standards, and linearity was found in the 9–45g/ml range with a regression value of 0.997% and RSD values of accuracy, precision, and robustness that were less than 2. In the HPLC method, the estimation of (VAL) was assessed on a Cosmosil C-18 (250mm4.6ID, Particle size: 5) column with Methanol:10mM KH2PO4 Buffer (50:50), 1 ml/min of flow rate, detection wavelength of 254nm, and the time of retention observed to be approximately 5.03 minutes with the assay value of 99.56%. Additionally, the HPLC technique was verified in accordance with ICH standards, and linearity was found in the 10–50g/ml range with a regression coefficient value of 0.998. Precision, accuracy, and robustness all had RSDs that were under 2%. Using Methanol:10mM KH2PO4 Buffer (50:50), the HPLC technique was also used to evaluate forced degradation at 254nm. It is clear from this study that the proposed methods for valacyclovir estimate in pharmaceutical preparation are quick, efficient, and specific. They may also be applied in routine analysis for the quantification of the drug in a dosage form.

Retinoic Acid Neutralizes the Effects of Herpes Simplex Virus Type 1-Infected Cell Protein 0 (ICP0) in Retinal Pigment Epithelial Cells.

Herpes simplex virus (HSV) infection of the cornea, uvea, and retina is the leading infectious cause of blindness worldwide. This study examined the effects of retinoic acid (RA) on the protein levels of interleukin (IL)-17A and IL-23 cytokines with known proinflammatory effects and toll-like receptor 3 (TLR3) messenger RNA (mRNA) expression in retinal pigment epithelial (ARPE-19) cells treated with HSV-1-infected cell protein 0 (ICP0). We used 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyl tetrazolium bromide assay to calculate the half maximal inhibitory concentration (IC50) doses of RA and ICP0 in ARPE-19 cells. At the end of 24 hours, protein levels of IL-17A and IL-23 were analyzed using enzyme-linked immunosorbent assay. TLR3 mRNA expression levels were also calculated using reverse transcription-polymerase chain reaction (RT-PCR). RA administration decreased IL-17A levels, which were elevated by ICP0. The IL-23 levels were similar between the ICP0-treated and control groups, but the difference was significant between the ICP0-treated group and RA+ICP0 combination. These results showed that RA can significantly increase IL-23 levels in the presence of ICP0. Although ICP0 dramatically increased TLR3 mRNA expression compared with that in the control group, the RA+ICP0 combination returned TLR3 mRNA expression to a level similar to that in the control group (P = 0.419). RA may potentially neutralize HSV-1 ICP0 negative effects in ARPE-19 cells.

Inhibitory effects of algal polysaccharide extract from Cladophora spp. against herpes simplex virus infection

Herpes simplex virus (HSV) is a causative agent of fever blister, genital herpes, and neonatal herpes. Nowadays, edible algae are recognized as health food due to high nutrition content and their many active compounds that are beneficial to health. The purpose of this study is to investigate the inhibitory effects of algal polysaccharide extract from Cladophora spp. against herpes simplex virus type 1 and type 2 on Vero cells. In this study, the structure of polysaccharide extract is presented as S=O and C–O–S of the sulfate group, as identified by the FT-IR technique. The toxicity of algal polysaccharide extract on Vero cells was determined by MTT assay. The algal extract showed low toxicity on the cells, with 50% cytotoxic concentration (CC50) value greater than 5000 µg mL−1. The inhibition of HSV infection by the algal extract was then evaluated on Vero cells using plaque reduction assay. The 50% effective concentration (EC50) values of algal extract exhibited antiviral activity against HSV-1 upon treatment before, during, and after viral adsorption with and without removal of the extract were 70.31, 15.17, > 5000 and 9.78 µg mL−1, respectively. Additionally, the EC50 values of algal extract against HSV-2 upon treatment before, during and after viral adsorption with, and without removal of the extract were 5.85, 2.57, > 5000 and 26.96 µg mL−1, respectively. Moreover, the algal extract demonstrated direct inactivation of HSV-1 and HSV-2 virions as well as inhibitory effect against HSV replication. Accordingly, algal polysaccharide extract containing sulfated polysaccharides showed strong activity against HSV. Therefore, it is proved to be useful to apply Cladophora spp. polysaccharide extract as an anti-HSV agent.