Valacyclovir Research Articles

Carbon Nano-Dots based potentiometric sensor for the assay of the antiviral agent; Valacyclovir: In-Depth DFT Calculations, application to the pharmaceutical formulation and greenness assessment

Valacyclovir (VAL), as a prodrug to acyclovir antiviral agent, has recently held a lot of interest for its efficacy boosting owing to the significant improvement in bioavailability. This makes it a successful candidate in the management of herpes simplex strains as well as CORONA viruses. In this work a carbon nano dot-modified glassy carbon electrode (GCE) has been optimized as potentiometric sensor for the assay of VAL through a systematic approach. A mixture components of polyvinyl chloride (PVC) membrane have been selected and fine-tuned for optimum sensitivity and selectivity. The best results have been obtained by drop casting a blend in % w/w of PVC; 30.85, tricrasyl phosphate (TCP) as plasticizer; 64.32, phosphotungstic acid (PT) as cation exchanger; 1.61 and phosphorus – nitrogen-doped carbon nano-dots (PNCDs); 3.22 over the GCE. The density function theory (DFT) calculations have been applied to the optimized structures of VAL and the CDs and have proven high binding affinity of 46 kcal/mol dominated by π-π stacking and hydrogen bonding. The developed sensor has exhibited a swift response time of six seconds at a 5.00 pH value. The ICH guidelines have been applied to validate the optimized parameters. A good linearity range has been obtained from 1.18 × 10-3 down to 1.07 × 10-6 M for a correlation coefficient 0.9996 with a Nernstian slope of 33.16 mV/decade. The greenness has been assessed using the AGREE approach, giving a score of 0.8, which has indicated the environmental friendliness. An average % recovery of almost 99.00 % was obtained by application to the tablet formulations and furtherly it has been monitored by the standard addition method, giving recoveries varied from 98.00 and up to 102.00 % for relative standard deviation values (%RSD) less than 1.50 %, evidencing efficiency for application in the quality control laboratories.

Recommendations for the selection of nucleoside analogues as antihuman herpesvirus drugs: a real-world analysis of reported cases from the FDA adverse event reporting system

ABSTRACT Objective The aim of this study is to provide guidance for refining medication protocols, developing alternative strategies, and enhancing protection against herpesvirus infections in personalized clinical settings. Methods Adverse drug events (ADEs) data for anti-herpesvirus from the first quarter of 2004 to the fourth quarter of 2022 were collected from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) methods for data mining. Results A total of 18,591, 24,206, 6,150, and 419 reports of ADEs associated with acyclovir (ACV), valacyclovir (VACV), ganciclovir (GCV), and famciclovir (FCV) were screened and extracted from the FAERS. In this study, the report summarized the high frequency and strong correlation of ADEs for the four drugs at the Preferred Term (PT) level. Additionally, the analysis also identified the relationship between ADEs and factors such as age, gender, and severity of outcome at the System Organ Class (SOC) level. Conclusion The safety reports for the four-nucleoside analogue anti-herpesvirus drugs are diverse and interconnected. Dosing for patients with herpesvirus infections should be tailored to their specific conditions and the potential risk of disease.

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.

Remission of HPV-Related Diseases by Antivirals for Herpesvirus: Clinical Cases and a Literature Review.

Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient's symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.

In Silico Identification of Novel HDAC2 Inhibitors for Reinstating Synaptic wiring in Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an increasing incidence rate. For the treatment of ASD, several pharmaceutical approaches, dietary supplements, and behavioral therapy have been proposed, but a definitive cure remains elusive. Histone deacetylases (HDACs) are critical epigenetic regulators whose molecular and pharmacological roles are being studied extensively in medically significant ailments such as neuropsychiatric disorders, neurodegenerative diseases, and cancer on a global scale. HDAC2's specific expression pattern in CNS makes it an appealing therapeutic target for neurological illnesses such as ASD.Methods: The study used PyRx software (version 0.8) to screen a library of 401 alkaloid compounds against HDAC2. In addition, the DS software was used to predict the physicochemical and DMET properties of the compound library.Results: Valaciclovir hydrochloride, Dihydrocapsaicin, Guanosine, Santacruzamate A, and 2'-Deoxyguanosine monohydrate compounds exhibited strong interactions with HDAC2. These compounds had a higher binding energy than the control compound, and they have promising drug-like properties and ADMET characteristics.Conclusion: These identified compounds could be used as HDAC2 inhibitors for the management of ASD, however, experimental research is needed to optimize them as HDAC2 inhibitors.Keywords: Autism spectrum disorder; Histone deacetylases; Alkaloid compounds; Drug-likeness

Clinical features of acyclovir encephalopathy without acute kidney injury

Few reports have described acyclovir (ACV) encephalopathy without acute kidney injury (AKI). This study clarified the clinical features of ACV encephalopathy without AKI compared to that with AKI. Creatinine (Cre) levels were measured on admission. After admission, Cre was measured in a timely manner for the first seven hospital days. The minimum Cre level in these measurements was then determined. ACV encephalopathy was defined when two criteria were met: 1) neurological symptoms appeared after valacyclovir (VACV) administration, and 2) neurological symptoms improved after VACV discontinuation. AKI was defined when the Cre level on admission was >1.5 times higher than the minimum Cre level. The subjects were divided into AKI and non-AKI groups based on these findings. Eighteen patients had ACV encephalopathy (5 males, mean age 81.3±5.5 years old). All patients were prescribed VACV 3,000 mg/day. The minimum Cre was 1.93±1.76 mg/dL. AKI occurred in 10 (56.6%) patients. VACV was discontinued in all patients, and emergency hemodialysis treatment was administered in 10 (55.6%) patients. All patients recovered. Compared to the AKI group, the non-AKI group had a lower history of taking a Ca-blocker (33.3% vs 80.0%, p=0.092), a lower rate of emergency dialysis (16.9% vs 70.0%, p=0.059) and a longer time to clinical improvement (3.67±1.86 vs 2.20±0.63 days, p=0.073). ACV encephalopathy without AKI is characterized by a low rate of emergency dialysis, which may be linked to a prolonged duration of symptoms.

Inhibitory effect on acute herpes and prevention of postherpetic neuralgia in herpes simplex virus-1-infected mice using Ricinus communis extract

Ricinus communis and valacyclovir (VACV) were tested for their effects on the progression of skin observation and pain responses in mice infected with herpes simplex virus type 1 (HSV-1). The mice were infected with HSV-1 and treated with R. communis (8, 16, or 48 mg/kg) or VACV (15, 45, or 90 mg/kg) twice daily from days 2 to 8 post-infection. Skin lesion development and pain-associated reactions were assessed 27 days after infection. HSV-1 infection resulted in zosteriform skin observation and increased pain-related scores. Both R. communis and VACV demonstrated a dose-dependent reduction in skin observation and pain-related ratings. The study also investigated the impact of the timing of R. communis and VACV administration on skin observation and pain responses and found that lesion scores were significantly reduced when R. communis treatment was initiated on day 2 post-infection. The inhibitory effects of R. communis and VACV on HSV-1 dissemination in the dorsal root ganglia were studied, showing a significant reduction in HSV-1 DNA replication number after the administration of both drugs. Additionally, the study aimed to investigate the impact of R. communis and VACV on the expression levels of pain-associated mRNA in the spinal cord of HSV-1-infected mice. The study demonstrated that R. communis therapy exhibited an inhibitory effect on pain-related factors.

Molecular and qualitative characterization of compatibility between valacyclovir hydrochloride and excipients as raw materials for the development of solid oral dosage formulation

Objectives: The objective of this present study is to know the compatibility of valacyclovir hydrochloride (VCH) with common excipients that would be utilized to develop solid oral dosage forms. Several spectroscopy techniques were used to know the possible interactions of VCH with excipients. More, a molecular docking study was also carried out to see the interaction of VCH with excipients. In vitro study of a physical mixture of VCH with excipients was executed to know the release of a drug. Material and Methods: Several analytical techniques such as differential scanning calorimetry, nuclear magnetic resonance spectrometer, and Fourier-transform infrared (FTIR) spectroscopy have been utilized to know the drug-excipient compatibility. Further, possible interactions between valacyclovir and different excipients were assessed by thin-layer chromatography. In vitro dissolution studies in different sets of experiments were done to determine the influence of the hydrophobic and hydrophilic nature of excipients (on the dissolution profile of VCH using USP II-type dissolving apparatus). Moreover, in silico molecular docking studies were also done to know any possible molecular interactions among drugs and excipients using AutoDock VINA 1.2.0 software and GROMACS 5.0 software. Results: FTIR and 1H NMR spectra of VCH and physical mixtures of VCH and excipients were compared and it was observed that no significant deviation of characteristic peaks in infrared spectroscopy and 1H NMR signals was detected. The endothermic peak of VCH in the physical mixtures of drugs and excipients was found in approximately the same position. In vitro dissolution studies displayed the influence of the hydrophobic and hydrophilic nature of excipients on the dissolution profile of VCH. For the physical mixture of VCH with lactose (LAC) and dicalcium phosphate (DP), % drug release was found to be 31.96% and 33.16% at 10 min, whereas the amount of % drug released for the mixture of VCH and talc was 25.00%. For two other excipients such as LAC and DP, the % drug release was determined to be 42.96% and 41.64%, respectively, for 30 min. The docking study also provided insights into the lowest energy conformations. Docking study anticipated that the number of interactions were more between valacyclovir and LAC (four nos.) in comparison to valacyclovir and microcrystalline cellulose (MCC) (two nos.). This interaction showed that in vitro drug release for the physical mixture of VCH with MCC was higher than a mixture of valacyclovir with LAC. Conclusion: A compatibility study of VCH by analytical techniques established that VCH was compatible with utilized excipients. Drug dissolution of VCH and physical mixture of MCC exhibited the maximum amount of drug release whereas a mixture of VCH with magnesium stearate released the minimum amount of drug for both short (10 min.) and long (30 min.) period. Docking studies disclosed that the LAC complex showed less deviation with less root mean square deviation value in comparison to the microcrystalline complex. Thus, the LAC complex has more hydrogen bonds and it was more stable as compared with the MCC complex. Therefore, VCH and used excipients could be used for solid dose formulations.

Cytomegalovirus Infection in Pregnancy Prevention and Treatment Options: A Systematic Review and Meta-Analysis.

Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and developmental delays among infected infants. Notably, this study examines CMV infection in pregnancy, its management, prevention mechanisms, and treatment options. Specifically, information from the Cochrane Library, PUBMED, Wiley Online, Science Direct, and Taylor Francis databases were reviewed along with additional records identified through the register, the Google Scholar search engine. Based on the search, 21 articles were identified for systematic review. A total of six randomized controlled trials (RCTs) were utilized for a meta-analytic review. As heterogeneity was substantial, the random effects model was used for meta-analysis. Utilizing the random-effects model, the restricted maximum likelihood (REML) approach, the estimate of effect size (d = -0.479, 95% CI = -0.977 to 0.019, p = 0.060) suggests the results are not statistically significant, so it cannot be inferred that the prevention methods used were effective, despite an inverse relationship between treatment and number of infected cases. The findings indicated that several techniques are used to prevent, diagnose, and manage CMV infection during pregnancy, including proper hygiene, ultrasound examination (US), magnetic resonance imaging (MRI), amniocentesis, viremia, hyperimmunoglobulin (HIG), and valacyclovir (VACV). The current review has significant implications for addressing CMV infection in pregnancy. Specifically, it provides valuable findings on contemporary management interventions to prevent and treat CMV infection among expectant mothers. Therefore, it allows relevant stakeholders to address these critical health concerns and understand the effectiveness of the proposed prevention and treatment options.

Enhanced Anti-Herpetic Activity of Valacyclovir Loaded in Sulfobutyl-ether-β-cyclodextrin-decorated Chitosan Nanodroplets.

Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments.

Separation and quantitation of valacyclovir enantiomers using stability‐indicating chiral liquid chromatography method with a chiral stationary phase of amylose tris‐(3,5‐dimethylphenylcarbamate)

AbstractThe present research developed and validated a new stability‐indicating technique for the stereo‐selectively enantiomers of the antiviral nucleoside analog Valacyclovir hydrochloride (VAL). The chiral separation was performed using normal‐phase high‐performance liquid chromatography (HPLC) with a chiral stationary phase consisting of amylose tris(3‐chloro‐5‐methylphenylcarbamate) and a mobile phase of “n‐hexane, methanol, ethanol, and diethylamine”, flow rate of 0.60 mL/min, column temperature of 30°C, injection volume of 10‐μL, detection wavelength of 254‐nm, and run time of 25‐min. The enantiomers (S‐enantiomer, L‐isomer, R‐enantiomer, and D‐isomer) of Valacyclovir were separated with a resolution of 4.8 and no interference. The validation parameters verified for the proposed method, linearity in a range of 0.1002–24.3486 μg/mL (0.02–4.86%) with a regression coefficient of 0.999, and the accuracy was determined with excellent recoveries ranging from 94.38%–109.97%. The concentrations established for the detection limit and quantitation limit were 0.01% and 0.02%, respectively. The forced degradation experiments were used to assess the stability‐indicating qualities. D‐Valacyclovir impurity was successfully evaluated in release and stability samples of VAL in drug substance and tablet dosage forms using the proposed normal phase chiral HPLC approach.

New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Development of manganese oxide nanoparticles based chemical sensor for sensitive determination of an antiviral drug valaciclovir

The electrochemical analysis of valaciclovir (VAL) was carried out by electro-deposition of manganese oxide nanoparticles on glassy carbon electrode (MnO2/GCE). The surface morphology of prepared sensor material was analysed by scanning electron microscopy (SEM). Effects of scan rate, solution pH, and concentration variation on the electrochemical behaviour of VAL were studied using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The increase in anodic current by the use of a modified electrode (5.76 μA) compared with the peak current of bare GCE (1.18 μA) confirms the enhancement of the surface area and catalytic property of manganese oxide nanoparticles. A linear response in the concentration of VAL was observed by DPV from 1.0 × 10−8 M to 14.0 × 10−6 M at the sensor. The limit of detection and quantification were found to be 0.95 nM and 3.17 nM, respectively. The real-world application of the sensor was validated by applying for pharmaceutical and real sample analysis. Thus, it has been proved that the proposed electrochemical sensor has a strong potential to be employed in quality control laboratories for the testing of pharmaceutical products.

Green RP-HPLC method for simultaneous determination of sofosbuvir, ledipasvir, velpatasvir antivirals and beyond in their bulk material and co-formulated products

In the present era, pharmaceutical industry is floated with the development of novel antiviral medications either in single or co-formulated pills. This growth of antiviral drug market is gaining the interest due to economic and therapeutic policies. Therefore, it is a real demand to validate analytical methods that monitor the entire standards considering their quality, safety and efficacy with maximum accuracy and maximum time and cost efficiency.HPLC offers a quick, automated, and highly accurate method to identify certain chemical components in a sample. Medical, forensic, bioavailability, environmental and manufacturing labs use the technique to quantify and separate the chemicals in a multicomponent sample. Consequently, an HPLC method is developed for quantitative analysis of a mixture containing five anti-viral agents namely, sofosbuvir (SF), ledipasvir (LD), velpatasvir (VL), daclatasvir (DC), and valacyclovir (VC) The method based on partitioning between reversed phase and methanol/water mobile phase with gradient elution at 1 mL/min flow rate and UV detection at 260 and 330 nm wavelengths along linear concentration ranges 5.00–80.00, 2.00–50.00, 5.00–50.00, 2.00–80.00 and 5.00–45.00 µg/ mL for SF, LD, VL, DC and VC, respectively.The greenness profile was assessed using Analytical Eco-scale and GAPI tools and found to be in agreement with the green analytical chemistry principles. The proposed method was validated experimentally and statistically and found to be a viable choice for single and multicomponent analysis in multi-tasks laboratory that consider the environmental impact and quality-cost balance with precision RSD% <2.00 % and accuracy ranging from 99.79 to 100.90 %.

Post-exposure prophylaxis to prevent varicella in immunocompromised children

SummaryBackgroundVaricella-zoster virus (VZV) infection can cause life-threatening events in immunocompromised patients. Post-exposure prophylaxis (PEP) is required to prevent secondary VZV infection. Limited evidence is available for the use of acyclovir (ACV)/valacyclovir (VCV) as PEP.MethodsHerein, we retrospectively analyzed immunocompromised paediatric patients with significant exposure to VZV. Patients administered PEP were categorized into four groups: 1) ACV/VCV group; 2) intravenous immunoglobulin (IVIG) group; 3) ACV/VCV/IVIG group; 4) vaccine group.ResultsAmong 69 exposure events, 107 patients were administered PEP (91, ACV/VCV; 16, ACV/VCV/IVIG) and 10 patients did not receive PEP (non-PEP group). The index case was diagnosed based on clinical symptoms in 55 cases (79.7%). Fourteen cases (20.3%) were confirmed using direct virological diagnostic procedures. In the PEP group, only 2 patients (2.2%) developed secondary VZV infections. Additionally, 2 patients in the non-PEP group (20.0%) developed secondary VZV infection. The incidence of secondary VZV infection was significantly lower in the PEP group than in the non-PEP group (P=0.036). Among patients administered PEP, no antiviral drug-induced side effects were detected.ConclusionsAntiviral agents administered as PEP are effective and safe for preventing VZV infections in immunocompromised patients. Rapid virological diagnosis of index cases might allow efficient administration of PEP after significant exposure to VZV infection.

Cerebral Organoids for Modeling of HSV-1-Induced-Amyloid β Associated Neuropathology and Phenotypic Rescue

Herpes simplex virus type I (HSV-1) infection is a potential risk factor involved in the Amyloid β (Aβ) associated neuropathology. However, further understanding of the neuropathological effects of the HSV-1 infection is hampered by the limitations of existing infection models due to the distinct differences between human brains and other mammalians’ brains. Here we generated cerebral organoid models derived from pluripotent stem cells to investigate the HSV-induced Aβ associated neuropathology and the role of antiviral drugs in the phenotypic rescue. Our results identified that the HSV-1-infected cerebral organoids recapitulated Aβ associated neuropathology including the multicellular Aβ deposition, dysregulated endogenous AD mediators, reactive gliosis, neuroinflammation, and neural loss, indicating that cerebral organoids offer an opportunity for modeling the interaction of HSV-1 with the complex phenotypes across the genetic, cellular, and tissue levels of the human Alzheimer’s disease (AD). Furthermore, we identified that two antiviral drugs, namely Ribavirin (RBV) and Valacyclovir (VCV), inhibited HSV-1 replication and rescued the neuropathological phenotypes associated with AD in the HSV-1-infected cerebral organoids, implying their therapeutic potential to slow down the progression of AD. Our study provides a high-fidelity human-relevant in-vitro HSV-1 infection model to reconstitute the multiscale neuropathological features associated with AD and discover therapeutic drug candidates relevant to the AD viral hypothesis.

Nano-Au particle decorated poly-(3-amino-5-hydroxypyrazole) coated carbon paste electrode for in-vitro detection of valacyclovir

A versatile reusable electrochemical biosensor has been formulated by using colloidal gold nanoparticle (AuNPs) suspension and conducting polymer poly-(3-amino-5-hydroxypyrazole (poly-AHP) modified carbon paste electrode (AuNPs/poly-AHP/CPE) for detection of an important anti-viral drug valacyclovir (VAL). A thin film of poly-AHP incorporated with homogeneous distribution of AuNPs on the surface of carbon paste electrode is fabricated stepwise by applying one by one. An electrochemical potentiodynamic polymerization of AHP was followed by a potentiostatic electrodissolution–induced deposition of AuNPs on poly-AHP. The sensor surface has been characterized by scanning electron microscopy (SEM), energy dispersive X-Ray spectroscopy (EDX), X-ray powder diffraction (XRD) and UV–visible spectroscopy for surface topological/morphological characteristics. Electrochemical efficiency of the present sensor system towards the detection of VAL is explored by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV) and hydrodynamic steady-state current–time analysis, and the fabricated AuNPs/poly-AHP/CPE is recognized as a capable sensor system for electrochemical determination of VAL. Applying DPV under optimized conditions, the anodic peak current exhibited a linear relationship against VAL over the range of 5–80 nM with a detection limit of as low as 1.9 nM and an analysis time of 15 s. Under hydrodynamic conditions mimicking flow-cell analysis, the low detection limit was as low as 2.5 nM (S/N > 4) with rapid analysis time of mere 5 s. Selective determination of VAL was performed in the presence of dopamine and serotonin. Practical utility of the AuNPs/poly-AHP film sensor has been demonstrated for the detection of VAL directly from artificial urine, pharmaceutical formulations and diluted human serum with good recovery limits.

Comparative Study of the Selectivity Power of Colorimetric Method Over Chromatographic Methods for the Analysis of Valaciclovir Hydrochloride.

Valaciclovir hydrochloride (VAL) is an essential antiviral prodrug used to cure various types of herpes. Analysis of VAL by different analytical techniques demonstrates a persuasive aspect that is favorable in quality control application. This study describes a comparison between colorimetric and chromatographic (RP-high performance liquid chromatography (HPLC) and thin-layer chromatography (TLC)-densitometric) methods concerning selectivity and specificity for the determination of VAL in all possible degradation products (alkali- and acid-induced degradation products, namely aciclovir [ACI] and guanine [GUA], respectively) in their synthetic mixture and pharmaceutical formulations. The colorimetric method was accomplished by forming a highly colored complex with ferric hydroxamate reagent measured at 493 nm in the concentration range (0.20-1.60 mg/mL). Both chromatographic methods were successfully applied using ultraviolet (UV) detection at 256 nm in the concentration range (2.00-5.00 µg/mL) for the RP-HPLC method and (10.00-900.00 ng/band) for the TLC-densitometric method. The linearity studies, regression equations, assay parameters, and validation sheet of the proposed colorimetric and chromatographic methods to determine VAL were obtained with highly acceptable values. The International Council for Harmonization (ICH) guidelines were followed to validate the described methods and the statistical comparison regarding both accuracy and precision, and satisfactory results were accomplished. In this study, we configure a full comparative study between different analytical methods for the analysis of challengeable mixture containing the drug of interest, VAL, along with its degradation products, ACI and GUA.

Antiviral drugs suppress infection of 2019-nCoV spike pseudotyped virus by interacting with ACE2 protein.

The outbreak of coronavirus disease 2019 (COVID‐19) has induced a large number of deaths worldwide. Angiotensin‐converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019‐nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID‐19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019‐nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the K D value of (4.33 ± 0.09) e−8, (6.29 ± 1.12) e−6, (2.37 ± 0.59) e−5, and (4.85 ± 1.57) e−5 M, respectively. But only ZDV and EFV prevent the 2019‐nCoV spike pseudotyped virus to enter ACE2‐HEK293T cells with an EC50 value of 4.30 ± 1.46 and 3.92 ± 1.36 μM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019‐nCoV infection of ACE2‐HEK293T cells by interacting with ACE2.

Kinetics and mechanistic investigations on antiviral drug-valacyclovir hydrochloride by heptavalent alkaline permanganate.

Kinetics of Permanganate (MnO4−) oxidation of antiviral drug, valacyclovir hydrochloride (VCH) has been studied spectrophotometrically at a constant ionic strength of 0.1 mol dm−3. The reaction exhibiting a 2:1 stoichiometry (MnO4−:VCH) has been studied over a wide range of experimental conditions. It was found that the rate enhancement was associated with an increase in concentrations of alkali, reductant and temperature. A plausible mechanism involving an intermediate Mn(VII)-VCH complex (C) was expected and rate law is derived accordingly. Calculated activation parameters also supported the anticipated mechanism.Graphic abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s12039-021-01969-4.