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.

Rapid diagnosis of herpes simplex virus 1 and 2 bloodstream infections utilizing a sample-to-answer platform.

Bloodstream HSV-1 and HSV-2 infections can cause devastating outcomes with high morbidity and mortality, especially in neonates or immunocompromised individuals. Proper patient management for herpes simplex virus (HSV) bloodstream infections is time-sensitive and requires a rapid, accurate, and definitive diagnosis. The absence of the U.S. Food and Drug Administration (FDA)-approved molecular assays for HSV detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the unmet need for improved diagnostics. We prospectively compared the cycle threshold values in paired samples including whole blood (WB), plasma, serum, and peripheral blood mononuclear cells (PBMCs) from patients with bloodstream HSV infections. This analysis employed a modified use of the FDA-cleared Simplexa HSV-1 & 2 Direct assay. The clinical performance in serum was assessed by comparing the results of 247 remnant specimens on this sample-to-answer platform to established laboratory-developed tests in a blinded fashion. Serum samples exhibited significantly lower cycle thresholds than whole blood samples [2.6 cycle threshold (Ct) bias, P < 0.001]. The modified Simplexa assay demonstrated 100% positive percent agreement for the detection of HSV-1 and HSV-2 DNA in serum samples and yielded an overall agreement of 95% (95% CI, 0.92 to 0.97), with a κ statistic of 0.75 (95% CI, 0.62 to 0.86) compared to the composite reference method. Discordance rates were 5.20% for HSV-1 and 0.81% for HSV-2. This investigation demonstrates that serum is an optimal specimen type for HSV detection when compared to several blood compartments. Serum offers a promising sample type for rapid and accurate diagnosis of HSV bloodstream infections using the modified Simplexa assay. IMPORTANCE: Rapid, accurate, and definitive diagnosis of herpes simplex virus (HSV) infections is crucial in clinical settings for patient management. The absence of FDA-authorized molecular assays for HSV-1/2 detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the need for improved diagnostic methods. Furthermore, rapid diagnosis of HSV bloodstream infections enables timely administration of antiviral treatment, influences patient management decisions for those at high risk, and can contribute to shorter hospital stays, thereby reducing healthcare costs.

Genital Herpes.

This JAMA Insights examines the history, diagnosis, prevention, and stigma of genital herpes infection in the US and explores treatments such as suppressive therapy.

Utilization of multiplex polymerase chain reaction for simultaneous and rapid detection of viral infections from different ocular structures.

The impact of viral keratitis (VK) on individuals and society is notable. Early diagnosis and treatment are crucial in managing viral keratitis effectively. Timely intervention with antiviral medications and supportive care can help mitigate the severity of the infection and improve visual outcomes. We examined the prevalence of varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), adenovirus (AdV) and herpes simplex virus type 2 (HSV-2) in patients suspected for ocular infections. Patients included in the study exhibited various clinical manifestations indicative of ocular pathology, such as infectious keratitis, corneal scar, endogenous endophthalmitis, panuveitis, endothelitis, stromal edema, and other relevant conditions. Four different types of tear fluid, corneal samples epithelium, aqueous humor and vitreous humor were taken. After genome extraction, multiplex real-time PCR was used for diagnosis of viruses. 48 (29.6%) out of the total of 162 (100%) eye specimen were positive. The dominant prevalence was VZV (12.3%) and HSV-1 (11.7%) followed by AdV (4.9%) and HSV-2 (0.6%). There were 4 (8.3%) coinfections within the samples (HSV-1 and VZV). Aqueous humor samples demonstrated superior virus detection ability and our only HSV-2 positive sample was from aqueous humor. The utilization of multiplex real-time PCR assays in differential diagnosis of VK holds promise for expeditious diagnoses while also preventing unwarranted antibiotic prescriptions. Moreover, the aqueous humor appears to be a more sensitive site for detecting viral keratitis.

Comparison of strain specific pathogenicity of Herpes Simplex Virus Type 1 by high-throughput sequencing.

Herpes Simplex Virus Type 1 (HSV-1) is a widespread human pathogen known for causing a spectrum of clinical manifestations, ranging from mild cold sores to severe complications like encephalitis. Understanding the strain-specific variations of HSV-1 is crucial for elucidating its pathogenesis and developing targeted therapeutic interventions. In this multifaceted study, we investigated the strain-specific characteristics of HSV-1 using an in vivo rat model. Firstly, a pilot study was conducted to assess the capacity of three HSV-1 strains (Fisher (F), KOS (K), and MacIntyre (M)) to induce cold sores in rats. Remarkably, the F strain exhibited pronounced pathogenicity, inducing erythema, swelling, and disrupted epidermis with ulceration, distinguishing it from the K and M strains. Subsequently, the treatment capability of intravenous acyclovir injection in HSV-1 F strain-infected rats was evaluated. Acyclovir treatment resulted in a significant reduction in HSV-1 viral copy numbers in serum and dissected neuronal tissues, particularly in the spinal cord, brain, and lower lip. Lastly, whole genome sequencing data revealed that high-impact mutations occurred in the K and M strains within the UL49, US2, and US3 genes. These mutations may play a pivotal role in influencing viral replication, dissemination, pathogenesis, and infectivity. In contrast, the moderate missense variant mutations detected in the US12, US8, UL3, UL30, UL31, and UL36 genes appeared to have no effect on viral pathogenesis and infectivity, based on RT-PCR data for spinal cord, trigeminal nerve, brain, and the lower lip. These strain-specific mutations underscore the dynamic nature of HSV-1 evolution. Collectively, our findings contribute to a deeper understanding of HSV-1 strain diversity and pave the way for the development of targeted therapeutic strategies against this medically significant virus.

Misdiagnosed as Fungal Keratitis: Herpes Simplex Virus-1 Keratitis Confirmed by Next-Generation Sequencing.

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

Diagnosis and management of a herpes nipple infection that resulted in neonatal HSV encephalitis.

We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up.

Evaluation of oral herpes simplex virus shedding among solid organ transplant recipients: A pilot study.

BACKGROUND: Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV-1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post-transplant) who were not taking daily antiviral suppressive therapy. METHODS: Participants self-collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary. RESULTS: Sample collection adherence was high (median 122 swabs/person, range: 85.7%-101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%-33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8-46.1 hrs). CONCLUSION: Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice-daily sampling may be sufficient to detect most episodes. These data show that self-collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population.

A case for implementing an HSV1/2, VZV, and syphilis lesion panel in Manitoba, Canada.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis.

Seroprevalence of herpes simplex virus type 1 (Herpesviridae: Simplexvirus: Human alphaherpesvirus 1) in smokers.

INTRODUCTION: Herpes simplex virus type 1 (HSV-1) is one of the most common human viral infections and has a double-stranded DNA genome belonging to the Herpesviridae family. Smoking is one of the leading causes of disease and premature death worldwide, responsible for the death of up to six million people annually. The purpose of the current study was to determine the seroprevalence of HSV-1 infection among smokers. Methods. The search strategy was conducted in the period from December 2022 to January 2023. The study included a random sample of 94 (88 males, and 6 females) healthy participants, aged between ≤ 20 to ≥ 60 years, with 50 participants as the control group. The HSV serological testing consisted of detecting antibodies to HSV-1 IgG with the help of ELISA. RESULTS: Most participants were university students, consisting of 45.7% males and 5.3% females, followed by employed smokers, consisting of 0.2% males and 1.1% females. The number of females was much lower than that of males reaching 6.4 and 93.6% respectively, due to customs and traditions. The seroprevalence was 24.47, 22.3 and 2.1% in males and females respectively. The seroprevalence rate was 13.8% in hookah and cigarette smokers, 9% in cigarette smokers and 1.1% in hookah smokers exclusively. The highest rate was observed in the age groups of 21-30 and 31-40 years with 12.80% and 7.40% respectively. CONCLUSIONS: The study revealed that the seroprevalence of HSV-1 IgG was 24.47%, and was higher among hookah and cigarette smokers compared to those who exclusively smoked cigarettes or hookah.

Herpes Simplex Virus Dacryoadenitis Preceding Skin Vesicles.

Herpes simplex virus involvement of the orbit is rare. We report the case of an immunocompetent patient who presented with preseptal edema, erythema, decreased vision, and dacryoadenitis prior to the appearance of vesicular skin lesions and in the absence of corneal dendrites. The patient's clinical picture failed to improve on empiric therapy with intravenous antibiotics. The patient subsequently developed skin vesicles and a nucleic acid amplification swab of the ocular surface was positive for herpes simplex virus-1. The patient demonstrated rapid clinical improvement after initiation of oral antivirals. This is an unusual case of presumed herpes simplex virus dacryoadenitis preceding skin vesicles in an immunocompetent patient.

Emergence of novel hypervirulent Acinetobacter baumannii strain and herpes simplex type 1 virus in a case of community-acquired pneumonia in China.

BACKGROUND: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. METHODS: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. RESULTS: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. CONCLUSIONS: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

Clinical features of atypical presentations of mucocutaneous herpes simplex virus infection observed in immunosuppressed individuals. Part II: the knife-cut sign.

The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.

Clinical features of atypical presentations of mucocutaneous herpes simplex virus infection observed in immunosuppressed individuals. Part I: herpetic geometric glossitis.

Herpetic geometric glossitis is a unique morphologic variant of HSV (herpes simplex virus) type 1 infection on the dorsum of the tongue that presents as an extremely painful linear central lingual fissure with a branched pattern. in the center of the tongue; there is a branched pattern of fissures that extend bilaterally from the central linear fissure. Herpetic geometric glossitis has been reported in 11 patients; 8 of these individuals were immunocompromised. Medical conditions and immunosuppressive medication treatment (7 patients) or only medical disorders (3 patients) or neither (1 patient) were present. HSV type 1 infection was diagnosed by viral culture in (7 patients), Tzanck preparation (2 patients) or clinically (2 patients). Mucocutaneous HSV infection at non-lingual locations--including the lips, labial mucosa, face and chest--were observed in 5 patients. All patients' symptoms and lesions responded to treatment with oral antiviral therapy: acyclovir (9 patients), famciclovir (1 patient) or valacyclovir (1 patient). The lingual pain and dorsal tongue fissures completely resolved completely within two to 14 days. In summary, herpetic geometric glossitis is a unique HSV type 1 infection, usually in immunocompromised patients, that occurs on the dorsal tongue and responds completely after treatment with orally administered antiviral therapy.

First parechovirus reported case in Saudi Arabia in hospitalized immunocompromised adult patient.

Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection.

Prevalence of yaws and syphilis in the Ashanti region of Ghana and occurrence of H. ducreyi, herpes simplex virus 1 and herpes simplex virus 2 in skin lesions associated with treponematoses.

Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases.

Serological Screening of TORCH Pathogen Infections in Infertile Women of Childbearing Age in Northwest China.

Serological screening for TORCH(Toxoplasma gondii [TOX], Rubella virus [RV], Cytomegalovirus [CMV], and Herpes simplex virus [HSV]) infections is an effective method for preventing congenital infections caused by TORCH pathogens.In this study, we retrospectively analyzed the characteristics of TORCH infections in 17,807 infertile women of childbearing age in northwest China.We conducted serological detection of TORCH-pathogen-specific IgM and IgG antibodies. The seroprevalence of TORCH infections was statistically analyzed by applying χ2 and Fisher exact-probability tests to evaluate the differences among ages and across quarters of the year. The overall IgM/IgG seroprevalences of TOX, RV, CMV, HSV-1, and HSV-2 were 0.46/3.4%, 0.77/84.93%, 0.68/97.54%, 1.2/82.83%, and 0.62/10.04%, respectively. The positive rates for RV-IgM in women ≥ 40 years old were significantly higher than those for women 25-39 (P < 0.05) years of age. The seroprevalence of HSV1-IgM was higher in the third and fourth quarters of the year (seasons) (P < 0.001), and the seroprevalence of CMV-IgG was statistically significant between differences quarters (P = 0.017), and the seroprevalence of CMV-IgG in the first quarter was lower than that in the third and fourth quarters (Bonferroni correction, P = 0.009 > 0.0083), suggesting no statistically significant difference between the latter two groups. This study showed that in northwestern China the risk of acquiring primary infection by a TORCH pathogen among infertile women of childbearing age were still high, especially Toxoplasma gondii and Herpesvirus type 2 infection. Therefore, effective prevention strategies that include serological screening for TORCH should be implemented.

Emerging drugs for the treatment of herpetic keratitis.

INTRODUCTION: Herpes simplex keratitis stands as a prominent factor contributing to infectious blindness among developed nations. On a global scale, over 60% of the population tests positive for herpes simplex virus type-1 (HSV-1). Despite these statistics, there is currently no vaccine available for the virus. Moreover, the conventional nucleoside drugs prescribed to patients are proving ineffective in addressing issues related to drug resistance, recurrence, latency, and the escalating risk of vision loss. Hence, it is imperative to continually explore all potential avenues to restrict the virus. This review article centers on the present treatment methods for HSV-1 keratitis (HSK), highlighting the ongoing clinical trials. It delves into the emerging drugs, their mode-of-action and future therapeutics. AREAS COVERED: The review focuses on the significance of a variety of small molecules targeting HSV-1 lifecycle at multiple steps. Peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and clinical trial websites. EXPERT OPINION: The exploration of small molecules that target specific pathways within the herpes lifecycle holds the potential for substantial impact on the antiviral pharmaceutical market. Simultaneously, the pursuit of disease-specific biomarkers has the capacity to usher in a transformative era in diagnostics within the field.