Herpes simplex virus (HSV) infections are widespread and cause a significant global health burden. Clinical manifestations range from herpes labialis and genital herpes to life-threatening herpes simplex encephalitis or neonatal herpes. Current treatment relies on nucleoside analogs such as acyclovir, valacyclovir or famciclovir. The emergence of resistance to these drugs is of concern in transplant recipients and immunocompromised patients. Next-generation helicase-primase inhibitors are under clinical development to provide more efficacious treatments and address resistance to current therapies. Adibelivir (IM-250) is a potent HSV helicase-primase inhibitor (HPI) with nanomolar activity against both HSV1 and HSV2. In the present study, we assessed the susceptibility of more than 50 clinical isolates and laboratory strains against adibelivir. Across all strains tested, adibelivir inhibited HSV replication in cell culture with mean EC50 values of 21 nM (HSV1) and 35 nM (HSV2), compared to up to 42-fold higher EC50 values for acyclovir (883 nM for HSV1 and 1456 nM for HSV2). No preexisting variants with a lack of susceptibility were identified. Furthermore, no cross-resistance was observed between nucleoside analogs and HPIs and finally, the antiviral activity depended on serum concentration and infectious dose. Collectively, these data establish the baseline susceptibility profile of HSV clinical isolates to adibelivir prior to its broader clinical introduction. Adibelivir retains activity against nucleoside-resistant HSV strains and exhibits synergistic antiviral effects when combined with acyclovir, penciclovir and foscarnet in vitro. These results support clinical evaluation of adibelivir as a therapeutic option for HSV infections and as a candidate for combination therapy.

Background/Objectives: Monkeypox is endemic to the African continent and has recently garnered global attention due to reported outbreaks in non-endemic nations. No approved drug is available for non-severe cases, and some isolates gained resistance to approved antivirals. In this study, we employed a drug repositioning strategy to evaluate the efficacy of existing FDA-approved antiviral drugs if repurposed for use against emerging Monkeypox, representing a cost-effective method for identifying novel therapeutic interventions. Methods: Methodology including Egyptian virus strain isolation, propagation and titration followed by in vitro studies, molecular docking and molecular dynamics simulations combined with binding free energy were carried out. Twenty-three FDA-approved drugs, including Abacavir, Acyclovir, Amantadine, Chloroquine, Daclatasvir, Dolutegravir, Entecavir, Favipiravir, Hydroxychloroquine, Lamivudine, Molnupiravir, Nevirapine, Oseltamivir, Penciclovir, Remdesivir, Ribavirin, Sofosbuvir, Tenofovir, Valaciclovir, Valganciclovir, Velpatasvir, Zanamivir, and Zidovudine, were screened for potential anti-monkeypox activity in vitro. In silico studies were carried out against three monkeypox proteins, Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13, to identify their potential targets. Results: In vitro testing showed that two antiviral drugs are positive. The employed computational methods indicate that remdesivir demonstrated superior binding patterns with elevated scores and stable complexes throughout the simulation. Conclusions: Our findings showed that Remdesivir therapeutic compound is potent against the tested strain of MPXV, and exhibited a robust binding affinity for Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13 enzymes, and thus may potentially be utilized as antiviral for the treatment of monkeypox virus.

Feline Infectious Rhinobronchitis (FVR) is a common and serious infectious upper respiratory disease. Famciclovir, an antiviral prodrug initially developed for human herpesviruses, demonstrates significant therapeutic efficacy in cats with FVR caused by feline herpesvirus type 1 (FHV-1).

Herpes simplex viruses (HSV) are extremely widespread pathogens that cause human infections of varying severity, from mild orofacial ulcerations of the skin and mucous membranes to life-threatening encephalitis and severe generalized forms of infection or recurrent herpetic corneal lesions leading to blindness. Standard treatment with acyclovir, penciclovir, or the corresponding prodrugs valacyclovir and famciclovir is usually sufficient to stop recurrent HSV infections. However, immunocompromised patients are of particular concern and often require long-term antiviral therapy. In such conditions, the risk of developing drug resistance, often cross-resistance increases significantly, since all basic antiherpetic drugs have a similar mechanism of action and affect the same drug target - viral DNA polymerase (DNA-pol). With the development of drug resistance, the effectiveness of treatment decreases, and it becomes necessary to switch to second-line drugs with severe side effects. Thus, it is necessary to develop new alternative treatment options. The creation of drugs aimed at a biotarget different from DNA-pol eliminates the risk of cross-resistance to acyclovir and related drugs, and their use in combination with traditional antiherpetic drugs can prevent or slow down the development of drug resistance in the virus. When combining drugs that affect the pathogen in different ways, it is important to maintain the therapeutic effect with the use of lower doses due to the synergistic nature of the interaction, which reduces the likelihood of developing unwanted side effects of drugs. The review presents current data on the state and possible prospects for the development of combination therapy for HSV infections, obtained as a result of searching the literature related to anti-herpetical therapy using the PubMed, Medline databases, RSCI, the international registry of clinical trials of the US National Institutes of Health.

Topical therapies with improved antiviral efficacy, bioavailability, and safety profiles are needed to combat blindness caused by herpes simplex virus type-1 (HSV-1) eye infections. Our previous work demonstrated that micron-sized high porosity activated carbon (HPAC) particles loaded with acyclovir (ACV), termed drug-encapsulated carbon (DECON), showed superior topical efficacy to ACV alone while reducing dosage frequency. Here, we advance our findings by utilizing a nanoparticle-based DECON (nanoDECON), which enhances cell permeability while maintaining DECON's nontoxic, cost-effective, and nonimmunogenic properties. Our assays demonstrate nanoDECON's low toxicity and nearly 100% loading of nucleoside analogs acyclovir, ganciclovir, and penciclovir. Drug release studies indicate that nanoDECON stably encapsulates these drugs with minimal passive release over 48 hours. Furthermore, antiviral studies with HSV-1-infected human corneal epithelial (HCE) cells show excellent antiviral activity at concentrations as low as 25 µg/mL. FITC-loaded nanoDECON illustrates a novel ability of this agent to deliver payloads into the cytoplasm and nucleus, as evidenced by confocal imaging. However, attempts to use nanoDECON for plasmid DNA delivery indicated poorer loading efficiency and a lack of GFP expression.

Feline herpesvirus type 1 (FHV-1) is a leading cause of ocular surface disease in cats, often requiring prolonged antiviral therapy. While oral famciclovir is effective, its use is limited by poor bioavailability and compliance challenges. This study evaluated the ocular tolerance and tear film pharmacokinetics of topical 1 % penciclovir cream (Fenlips®), an FDA-approved dermatologic formulation repurposed for ophthalmic use in cats. A retrospective survey of owners whose cats were treated with Fenlips® revealed high levels of satisfaction, with 85 % reporting no adverse effects and 80 % rating the treatment as effective or highly effective. To further assess safety and pharmacokinetics, two prospective studies were conducted in seven healthy domestic cats. In the first, Fenlips® was applied to one eye and artificial tears (DuraTears®) to the other eye for 10 days. No significant differences were observed between eyes in clinical scores, tear production, or tear film stability. Corneal sensitivity increased significantly in Fenlips®-treated eyes. In the second study, tear fluid samples collected over 24 h revealed that penciclovir concentrations remained above the minimal inhibitory concentration (0.30 μg/ml) for FHV-1 for over 8 h on average, with a terminal half-life of 8.75 h. These findings indicate that Fenlips® is well tolerated and achieves pharmacologically relevant concentrations in the tear film, supporting its potential use as a twice-daily topical treatment for herpetic keratoconjunctivitis in cats.

Herpes labialis (HL) is a common viral infection of the lips, primarily caused by herpes simplex virus type1. Although conventional treatment for HL primarily consist of antiviral agents, photobiomodulation therapy (PBMT) has also emerged as an effective intervention. This study aims to compare PBMT with conventional treatment for HL. A systematic review of randomized controlled trials (RCTs) was conducted through Cochrane Library, PubMed, Semantic Scholar, Dimension AI and Web of Science in accordance to PRISMA guidelines. English language RCTs reporting comparison of PBMT with conventional treatment (i.e., acyclovir, valacyclovir, and penciclovir) in HL were eligible, without restriction on patient's age and publication year. The primary outcomes were pain (on visual analog scale: VAS), healing time (in days) and HL lesion size (in cm[2]). Cochrane's Risk of Bias (RoB) 2.0 tool and RevMan 5.0 was used for quality appraisal and conducting meta-analysis of the selected RCTs, respectively. Six RCTs involving [2]60 HL patients (PBMT: 129, conventional treatment: 131) were included. Pain score at day 2 and 3 after treatment showed an overall effect favoring the PBMT with a standardized mean difference (SMD) of [-1.54 (95% CI: -2.32 to -0.77; Z = 3.92, p < 0.001] and [-0.88 (95% CI: -1.19 to -0.57; Z = 5.62, p < 0.001], respectively. The pooled data revealed that PBMT resulted in significantly faster healing of the HL lesions [1.22 days (95% CI: -1.93 to -0.51; p = 0.0007). At day 3 after treatment, a significantly higher decrease in the lesion size was observed for patients receiving PBMT compared conventional treatment [-0.99 cm[2] (95% CI: -1.41 to -057; p < 0.0001)]. The overall RoB score for 05 RCTs revealed High risk of bias, primarily arising from domain 5 of the RoB 2.0 tool. PBMT demonstrated significant reduction in pain, healing time and lesion size, as compared to conventional treatment, though smaller number of available RCTs warrants further investigation.

The residues of antiviral drugs acyclovir (ACV), penciclovir (PCV) and ganciclovir (GCV) in foods, particularly in ready-to-eat products, pose a significant threat to human health, making it urgent to develop a rapid and sensitive method for their detection. Herein, we designed a novel magnetic molecularly imprinted three-dimensional covalent organic framework (MICOF@Fe3O4) for selective extraction of these antiviral drugs from complicated food matrix. The prepared MICOF@Fe3O4 integrates molecular recognition ability, 3D COF structural advantages and magnetic responsiveness, providing high selectivity, large adsorption capacity and facile operation for magnetic solid-phase extraction (MSPE). Afterwards, a MSPE-UHPLC-MS/MS method was developed, which stands out as the most sensitive approach yet for ACV, PCV, GCV measurements and has been successfully applied to analyze thirteen ready-to-eat chicken samples. Endogenous PCV was detected in two of these samples, demonstrating the potential of the proposed method as a valuable tool for monitoring antiviral drug residues and ensuring food safety.

This study aimed to enhance the residence time of penciclovir on the skin by developing controlled-release microsponges to improve therapeutic efficacy for the treatment of cold sores. Microsponges were prepared using the quasi-emulsion solvent diffusion method. Ethyl cellulose was selected as the internal phase polymer, and dichloromethane was chosen as the solvent based on preliminary studies. A 3[2] full factorial design was employed to optimize the formulation, with polyvinyl alcohol as the stabilizer in the external phase. The optimized formulation achieved an entrapment efficiency of 76.56%, particle size of 64.12 µm, and prolonged drug release over 15 h. SEM analysis confirmed spherical, porous microsponge morphology, while stability studies demonstrated consistent performance over 3 months with an F2 value of 84.79, indicating formulation stability. The study successfully developed penciclovir-loaded microsponges with high entrapment efficiency and prolonged drug release characteristics. The formulation demonstrated prolonged drug release characteristics, indicating potential suitability for controlled-release topical application.