Acyclovir Research Articles

Increased human immunodeficiency virus viral load with cerebral infarction due to varicella zoster virus vasculopathy on treatment with bictegravir/emtricitabine/tenofovir alafenamide suspension: a case report and literature review

BackgroundVaricella-Zoster virus (VZV) vasculopathy occasionally occurs in immunocompromised patients and is difficult to treat. The risk factor and optimal therapy remain unclear. Patients with human immunodeficiency virus (HIV) and dysphagia or difficulty in oral intake receive antiretroviral therapy (ART) suspension. However, there remains little evidence regarding ART suspension.Case presentationWe experienced a case of a 55-year-old man diagnosed with HIV and severe multiple cerebral infarctions due to VZV vasculopathy. We started on bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and acyclovir (ACV), and prednisone. He was started on BIC/TAF/FTC suspension because of deteriorated swallowing. The HIV viral load was increased; however, no drug-resistance genes were detected. We successfully treated him with doltegravir/abacavir/lamibudine suspension. We performed two literature reviews of the administration of BIC/TAF/3TC suspension and VZV vasculopathy in patients with HIV. Three cases of BIC/TAF/3TC suspension were considered treatment failures. Recent history of VZV infection and a CD4 count under 200 μL may be risk factors for VZV vasculopathy. The effective treatment may be using steroid and ACV; however, treatment duration could differ.ConclusionsBIC/TAF/FTC suspension administration may be unstable, and treating ACV and steroid may be optimal therapy for VZV vasculopathy; however, the evidence level is low.

Acyclovir-resistant HSV-1 isolates among immunocompromised patients in southern Taiwan: Low prevalence and novel mutations.

Herpes simplex virus type 1 (HSV-1) can establish latency in humans and easily relapse in immunocompromised patients, with significant mortality. Treatment with acyclovir (ACV) can result in the emergence of HSV resistance. A total of 440 frozen HSV-1 isolates collected from 318 patients from January 2014 to July 2019 were obtained from National Cheng Kung University Hospital in southern Taiwan. These 440 isolates were subjected to phenotypic studies for ACV-resistance by initial screening with the plaque reduction assay (PRA) and further validation by the DNA reduction assay (DRA). The ACV-resistant strains were further investigated by Sanger sequencing for the full-length UL23 and UL30 genes, which encode thymidine kinase and DNA polymerase, respectively. Hematological malignancies or hematopoietic stem-cell transplantation patients accounted for 56.9% (124/218) among the immunocompromised patients (218/318) in this study. Repeated sampling for HSV testing was 50% (109/218) in immunocompromised patients. Only 1.38% (3/218) of immunocompromised patients and 0.9% (3/318) of all patients developed ACV-resistant HSV-1 as measured by phenotypic screening assays. It is noteworthy that a novel Y248D mutation in the UL23 gene from an immunocompromised patient was found by both PRA and DRA. In 3D protein predicting analysis, uncharged Y248 was located at an alpha-helix and substituted by negative-charged D248, which may alter the function of viral thymidine kinase. Besides, three unreported mutations related to natural polymorphism were found in virus isolates from two immunocompetent patients, including 683-688 deletion, R227H, and A351D in the UL30 gene. These data show that the prevalence of ACV-resistant HSV-1 among immunocompromised patients in southern Taiwan is low. These results will be helpful for the clinical management and treatment of HSV infections.

In vitro and silico studies of geraniin interfering with HSV-2 replication by targeting glycoprotein D

Residues ASN94 and GLN41 presented the highest frequency in molecular docking tests. The geraniin-glycoprotein D(gD) complexes was stable with RMSD(root mean square deviation)value less than 0.3 nm. The Molecular dynamic (MD) simulations revealed stable hydrogen bonds between gD and geraniin. Root mean square fluctuation (RMSF) values were less than 0.15 nm around the interface of geraniin-gD complex. In virucidal assays showed a much higher anti-HSV-2 inhibition activity of geraniin as compared to acyclovir(ACV).Human immunodeficiency virus transactivator (HIV-TAT) treatment significantly enhanced HSV-2 replication and lethal effect on HaCaT cells. The inhibitory rate of geraniin against HSV-2 coinfected with HIV-TAT was significantly decreased. The immunofluorescence results also revealed that HSV-2 gD expression presented a green fluorescence on HaCaT cells membranes and showed clear downregulation in geraniin-treated cells, but was expressed clearly on cell membranes under geraniin, HSV-2 and HIV-TAT cotreatment. The anti-apoptotic effect from geraniin persisted after 72 h, while the anti-apoptotic effect from geraniin diminished when HIV-TAT and geraniin were combined.

The carbon-doped Fe3O4 montmorillonite particle electrode for the degradation of antiviral drugs in electro-Fenton system

Since the outbreak of COVID-19, the extensive use of epidemic control drugs such as Arbidol (ARB) and Acyclovir (ACV) has significantly increased and the environmental pollution caused by these residues has attracted increasing attention. In this article, a novel montmorillonite graphene-like carbon hybrid Fe3O4 compound (Mt/GH/Fe3O4) as particle electrode catalyst was prepared and applied in three-dimensional-electro-Fenton (3D-EF) for the ARB and ACV degradation. The structure and composition of the compound catalyst were characterized. The degradation efficiency of targets was significantly increased in the 3D-EF degradation system and even more thorough for the degradation of targets, compared with simple 2D, 3D, and EF catalytic degradation systems. The degradation rate of antiviral drugs can reach >90% in 5 min with excellent stability. The research demonstrated that the clay mineral with a special structure loaded with graphene-like carbon and Fe3O4 had supplied an ideal reaction medium for the electro-Fenton reaction. Mt./GH/Fe3O4-based 3D-EF degradation system would have promising applications in the degradation and removal of antiviral drug residuals in the environment.

Novel UL23 and UL30 substitutions in HSV1 and HSV2 viruses related to polymorphism or drug resistance

Data on herpes simplex virus (HSV) polymorphism as well as acyclovir (ACV) and foscarnet (FOS) resistance mutations are not exhaustive and may hinder accurate diagnosis by next-generation sequencing (NGS). Here, we report novel UL23 and UL30 substitutions for HSV1 and HSV2 identified in immunocompromised patients treated for hematological malignancies during the last 6 years of HSV resistance surveillance at the University Hospital of Lyon. For HSV1, 35 novel UL23 substitutions and 52 novel UL30 substitutions were identified. For HSV2, 2 novel UL23 substitutions and 12 novel UL30 substitutions were identified. These results allow to complete the database of HSV1 and HSV2 substitutions, related either to polymorphism or to ACV and FOS resistance.

Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer.

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.

Ultrasound-assisted dispersive liquid-liquid microextraction approach for preconcentration of acyclovir as antiviral drug in dosage forms prior to spectrophotometric determination

ABSTRACT. For acyclovir (ACV) determination in bulk and dosage forms, quick, sensitive, straightforward, and eco-friendly ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME)-based spectrophotometric method has been created and validated. ACV with 1,2-naphthoquine-4-sulfonate (NQS) react in alkaline medium to produce a yellow-colored product, which is the basis of the newly created method. Investigation and optimization were done on the crucial experimental variables influencing ACV's extraction effectiveness. At λmax = 495 nm, the minuscule organic droplets were detected. The linearity was present from 0.1 to 3.0 μg/mL under ideal circumstances, with a linear correlation coefficient of 0.9995. The detection limit was 0.03 μg/mL and quantification limit was 0.1 μg/mL. 22.50 was the enrichment factor. Relative standard deviation (RSD%) as accuracy at 2.0 μg/mL of ACV was 1.0%, with good recovery (99.30%). The developed UA-DLLME method was effectively used to determine the ACV in dosage forms, and the validation was evaluated. Results from the suggested technique for dosage forms and pure ACV were in excellent agreement with the results from the official method.
 
 KEY WORDS: Ultrasound-assissted, Dispersive liquid–liquid microextraction, Acyclovir, Spectrophotometry, Dosage forms
 Bull. Chem. Soc. Ethiop. 2023, 37(5), 1081-1092. 
 DOI: https://dx.doi.org/10.4314/bcse.v37i5.2

Three-dimensional heterogeneous electro-Fenton system with reduced graphene oxide based particle electrode for Acyclovir removal

New pollutant pharmaceutical and personal care products (PPCPs), especially antiviral drugs, have received increasing attention not only due to their increase in usage after the outbreak of COVID-19 epidemics but also due to their adverse impacts on water ecological environment. Electro-Fenton technology is an effective method to remove PPCPs from water. Novel particle electrodes (MMT/rGO/Fe3O4) were synthesized by depositing Fe3O4 nanoparticles on reduced graphene oxide modified montmorillonite and acted as catalysts to promote oxidation performance in a three-dimensional electro-Fenton (3D-EF) system. The electrodes combined the catalytic property of Fe3O4, hydrophilicity of montmorillonite and electrical conductivity of graphene oxides, and applied for the degradation of Acyclovir (ACV) with high efficiency and ease of operation. At optimal condition, the degradation rate of ACV reached 100% within 120 min, and the applicable pH range could be 3 to 11 in the 3D-EF system. The stability and reusability of MMT/rGO/Fe3O4 particle electrodes were also studied, the removal rate of ACV remained at 92% after 10 cycles, which was just slightly lower than that of the first cycle. Potential degradation mechanisms were also proposed by methanol quenching tests and FT-ICR-MS.

Surface-Enhanced Raman scattering (SERS) filter paper substrates decorated with silver nanoparticles for the detection of molecular vibrations of Acyclovir drug

Acyclovir (ACV) drug, a common antiviral agent, is frequently used as the primary clinical treatment method for treating hepatitis B, herpes simplex, and varicella zoster viruses due to its potent therapeutic effect. In patients with compromised immune systems, this medication can stop cytomegalovirus infections, and high doses of this drug are required; however, such prescription leads to kidney toxicity. Therefore, timely and accurate detection of ACV is crucial in many areas. Surface-Enhanced Raman Scattering (SERS) is a reliable, rapid, and precise approach for the identification of trace biomaterials and chemicals. Filter paper substrates decorated with silver nanoparticles (AgNPs) were applied as SERS biosensors to detect ACV and control its adverse effects. Initially, a chemical reduction procedure was utilized to produce AgNPs. Afterward, UV–Vis, FE-SEM, XRD, TEM, DLS, and AFM were employed to examine the properties of prepared AgNPs. In order to prepare SERS-active filter paper substrates (SERS-FPS) to detect Molecular vibrations of ACV, AgNPs prepared by immersion method were coated on filter paper substrates. Moreover, the UV–Vis DRS analysis was carried out to assess the stability of filter paper substrates and SERS-FPS. The AgNPs reacted with ACV after being coated on SERS-active plasmonic substrates and could sensitively detect ACV in small concentrations. It was discovered that the limit of detection of SERS plasmonic substrates was 10-12 M. Moreover, the mean RSD for ten repeated tests was calculated as 4.19%. The enhancement factor for detecting ACV using the developed biosensors was calculated to be 3.024 × 105 and 3.058 × 105 experimentally and via simulation, respectively. According to the Raman results, SERS-FPS for the detection of ACV, fabricated by the present methods, showed promising results for SERS-based investigations. Furthermore, these substrates showed significant disposablity, reproducibility, and chemical stability. Therefore, the fabricated substrates are capable to be employed as potential SERS biosensors to detect trace substances.

Effects of storage conditions on permeability and electrical impedance properties of the skin barrier

The aim of this study was to investigate the effect of various skin preservation protocols on in vitro drug permeation, epidermal-dermal drug distribution, and electrical impedance properties of skin membranes. Acyclovir (AC) and methyl salicylate (MS) were selected as model drugs due to their different physicochemical properties and skin metabolic profiles. In particular, AC is relatively hydrophilic (logP −1.8) and not expected to be affected by skin metabolism, while MS is relatively lipophilic (logP 2.5) and susceptible to metabolism, being a substrate for esterase residing in skin. Skin from pig ears was used and freshly excised into split-thickness membranes, which were divided and immediately stored at five different storage conditions: a) 4 °C overnight (fresh control), b) 4 °C for 4 days, c) and d) −20 °C for 6 weeks and one year, respectively, and e) −80 °C for 6 weeks. Based on the combined results, general trends are observed showing that fresh skin is associated with lower permeation of both model drugs and higher skin membrane electrical resistance, as compared to the other storage conditions. Interestingly, in the case of fresh skin, significantly lower amounts of MS are detected in the epidermis and dermis compartments, implying higher levels of ester hydrolysis of MS (i.e., higher esterase activity). In line with this, the concentration of salicylic acid (SA) extracted from the dermis is significantly higher for fresh skin, as compared to the other storage conditions. Nevertheless, for all storage conditions, substantial amounts of SA are detected in the receptor medium, as well as in the epidermis and dermis, implying that esterase activity is maintained to some extent in all cases. For AC, which is not expected to be affected by skin metabolism, freeze storage (protocols c-e) is observed to result in higher accumulation of AC in the epidermis, as compared to the case of fresh skin, while the AC concentration in dermis is unaffected. These observations can be rationalized primarily by the observed lower permeability of fresh skin towards this hydrophilic substance. Finally, a strong correlation between AC permeation and electrical skin resistance is shown for individual skin membranes irrespective of storage condition, while the corresponding correlation for MS is inferior. On the other hand, a strong correlation is shown for individual membranes between MS permeation and electrical skin capacitance, while a similar correlation for AC is lower. The observed correlations between drug permeability and electrical impedance open up for standardizing in vitro data for improved analysis and comparisons between permeability results obtained with skin stored at different conditions.

Fabrication of RuNPs/TBA/PGE and its application for the electrochemical determination of trace amounts of acyclovir

In this work, a pencil graphite electrode modified by ruthenium nanoparticles and thiobarbituric acid (RuNPs/TBA/PGE) was used to measure the acyclovir (ACV) using a sensitive adsorptive differential pulse voltammetric technique)AdDPV). Field emission scanning electron microscopy (FESEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to characterize the modified electrode. Some concentration and instrumental factors affecting the electrode response in the ACV measurement were optimized, and ACV was determined under optimized conditions in two concentration ranges: 3.0 to 30.0 and 30.0 to 3000.0 nM. The detection limit was also determined to be 0.8 nM. Finally, the proposed method was used to measure ACV in tablet and urine samples, and the results showed that the proposed method has the necessary accuracy and precision.

Preparation and Characterization of Poly(vinyl acetate-co-2-hydroxyethyl methacrylate) and In Vitro Application as Contact Lens for Acyclovir Delivery.

A series of poly(vinyl acetate-co-2-hydroxyethylmethacrylate)/acyclovir drug carrier systems (HEMAVAC) containing different acyclovir contents was prepared through bulk free radical polymerization of 2-hydroxyethyl methacrylate with vinyl acetate (VAc) in presence of acyclovir (ACVR) as the drug using a LED lamp in presence of camphorquinone as the photoinitiator. The structure of the drug carrier system was confirmed by FTIR and 1HNMR analysis, and the uniform dispersion of the drug particles in the carrier was proved by DSC and XRD analysis. The study of the physico-chemical properties of the prepared materials, such as the transparency, swelling capacity, wettability and optical refraction, was carried out by UV-visible analysis, a swelling test and measurement of the contact angle and the refractive index, respectively. The elastic modulus and the yield strength of the wet prepared materials were examined by dynamic mechanical analysis. The cytotoxicity of the prepared materials and cell adhesion on these systems were studied by LDH assay and the MTT test, respectively. The results obtained were comparable to those of standard lenses with a transparency of 76.90-89.51%, a swelling capacity of 42.23-81.80% by weight, a wettability of 75.95-89.04°, a refractive index of 1.4301-1.4526 and a modulus of elasticity of 0.67-1.50 MPa, depending on the ACVR content. It was also shown that these materials exhibit no significant cytotoxicity; on the other hand, they show significant cell adhesion. The in vitro dynamic release of ACVR in water revealed that the HEMAVAC drug carrier can consistently deliver uniformly adequate amounts of ACVR (5.04-36 wt%) over a long period (7 days) in two steps. It was also found that the solubility of ACVR obtained from the release process was improved by 1.4 times that obtained by direct solubility of the drug in powder form at the same temperature.

Isolation, typing, and acyclovir susceptibility of human herpesvirus 1 and 2 detected in Rio de Janeiro, Brazil

OBJECTIVES: To isolate and identify human herpesvirus (HHV) strains circulating in healthy individuals in Rio de Janeiro, Brazil, and characterize their acyclovir (ACV) susceptibility.

Degradation of antiviral drug acyclovir by thermal activated persulfate process: Kinetics study and modeling

Pharmaceutical and personal care products (PPCPs) pose a great threat to water environment security. In this study, acyclovir (ACV) was efficiently degraded by thermally activated persulfate (TAP) system. The ACV degradation increased with rising reaction temperature and persulfate dosage. With the existence of inorganic anions and humic acid, ACV removal was retarded to varying degrees. Under strong alkaline condition, it was observed that the degradation of ACV was significantly inhibited. In addition, Kintecus software was employed to simulate ACV removal and achieved a good fit with the experimental results. The contribution rates of main reactive radicals under acidic, neutral, and alkaline conditions were investigated, and the contribution of hydroxyl radical (⋅OH) increased significantly under alkaline condition. The main active species were identified as sulfate radical (SO4⋅-) and ⋅OH through quenching experiment, and the second-order reaction rate constants of SO4⋅- and ∙OH reacted with ACV were calculated to be 9.17 × 109 M−1 s−1 and 2.74 × 109 M−1 s−1, respectively. The main degradation pathways included addition of free radicals, oxidation of branch chain and ring opening. The acute and chronic toxicity of intermediates to organisms predicted by ECOSAR were significantly reduced compared with that of ACV.

Electropolymerized Melamine on Electrochemically Reduced Graphene Oxide: Growth Mechanistics, Electrode Processing, and Amperometric Sensing of Acyclovir.

Metal-free, cost-efficient, redox-active electrode materials, combining graphene derivatives with nitrogen-rich polymelamine (PM), are widely explored as an interface layer for electrocatalysis and an electrochemical sensor platform. However, conventional chemical routes often yield derivatives of PM suffering from impaired redox behavior, restricting their electron-transfer kinetics. Herein, an optimal potentiodynamic method has been established to electrodeposit PM on electrochemically reduced graphene oxide (ErGO). A supporting electrolyte, containing Cl-, enhances the formation of intermediates NH3+ and ═NH2+ at the monomeric melamine, eventually interacting with the residual oxygenated functional groups of ErGO to form PM. In situ Raman spectrum analysis revealed the influence of the defective area and the graphitization ratio on the ErGO surface during the course of electropolymerization of melamine. Under optimal electrodeposition conditions (E = 0-1.6 V; ν = 0.1 V/s), the amount of electrodeposited PM on the ErGO surface was determined to be 16.5 μg/(cycle·cm2), using electrochemical quartz crystal microbalance analysis. An ErGO-PM-modified glassy carbon electrode (GCE) and a screen-printed electrode exhibit the direct electrooxidation of acyclovir (ACV). Amperometric analyses of ErGO-PM-modified electrodes exhibited the lowest detection limit of 137.4 pM with analytical robustness, rapid steady state, and reproducibility promising for ACV detection in complex biological matrices.

Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation.

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol-gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63-75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen-Crowell's kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.

Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir.

Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed.

A Dual‐Function Electrospun Matrix for the Prevention of Herpes Simplex Virus‐1 Infections after Corneal Transplantation

Tissue transplantations are often associated with severe infections. Cornea replacement as the most frequent transplantation worldwide bears the risk of keratitis caused by herpes simplex virus (HSV), posing a severe and sight‐threatening complication. To overcome the current lack of effective HSV therapy in the eye, biodegradable nanofibrous scaffolds incorporating acyclovir (ACV) intended for transplantation along with the cornea graft to prevent viral infections are designed. The rational development of these matrices reveals the strong dependency of the surface wettability on the release kinetics of the tested biocompatible poly(lactic‐co‐glycolic acid) (PLGA) polymers. Using a mixture of two PLGA polymers, a tailor‐made release of the antiviral active ACV is achieved for the intended treatment period. In a human in vitro HSV infection model, a synergistic viral inhibition mechanism by binding the virus particles on the fibers surface, while simultaneously releasing the antiviral active, could be confirmed. Besides the controlled ACV release, the polymer fibers bind virus particles to their surface, significantly reducing the virus titer. Based on this tunable dual effect, the fiber scaffolds exhibit a promising antiviral drug delivery platform, which can overcome the limitations of current infection therapy associated with cornea transplantation.

Effect of castalagin against HSV-1 infection in newborn mice

We tested in vivo anti-herpetic effect of castalagin, an ellagitannin compound, extracted from pedunculate oak (Quercus robur). Previous investigations found that castalagin possesses a strong inhibitory effect in vitro against HSV-1/2 equal to acyclovir (ACV). It is also effective against ACV-resistant mutants and shows a synergistic effect with ACV. We study castalagin’s activity towards HSV-1 infection in newborn mice. Acute toxicity determination in mice showed LD50 value of 295 mg/kg. Prolonged toxicity was also constructed. Castalagin manifested a marked activity against HSV-1 (LD90/0.02 ml) administered in 7-day course at 0.02 ml s.c. doses of 7.5 or 10 mg/kg (PI 57-58%). ACV course demonstrated a marked activity at 20 mg/kg. The selectivity ratio LD50/ED50 (295/7.5) could be accepted as ≥ 33.

Ethanol extract from Artemisia argyi leaves inhibits HSV-1 infection by destroying the viral envelope

Herpes simplex virus type 1 (HSV-1) is a widely disseminated virus that establishes latency in the brain and causes occasional but fatal herpes simplex encephalitis. Currently, acyclovir (ACV) is the main clinical drug used in the treatment of HSV-1 infection, and the failure of therapy in immunocompromised patients caused by ACV-resistant HSV-1 strains necessitates the requirement to develop novel anti-HSV-1 drugs. Artemisia argyi, a Traditional Chinese Medicine, has been historically used to treat inflammation, bacterial infection, and cancer. In this study, we demonstrated the antiviral effect and mechanism of ethanol extract of A. argyi leaves (hereafter referred to as ‘AEE’). We showed that AEE at 10 μg/ml exhibits potent antiviral effects on both normal and ACV-resistant HSV-1 strains. AEE also inhibited the infection of HSV-2, rotavirus, and influenza virus. Transmission electron microscopy revealed that AEE destroys the membrane integrity of HSV-1 viral particles, resulting in impaired viral attachment and penetration. Furthermore, mass spectrometry assay identified 12 major components of AEE, among which two new flavones, deoxysappanone B 7,3ʹ-dimethyl ether, and 3,7-dihydroxy-3′,4ʹ-dimethoxyflavone, exhibited the highest binding affinity to HSV-1 glycoprotein gB at the surface site critical for gB–gH–gL interaction and gB-mediated membrane fusion, suggesting their involvement in inactivating virions. Therefore, A. argyi is an important source of antiviral drugs, and the AEE may be a potential novel antiviral agent against HSV-1 infection.