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Brazilian Journal of Microbiology :... Sep 2023Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as...
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient's immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products' bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC) and inhibitory (IC) concentrations of 50% and the selectivity index (SI: CC/IC) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.
Topics: Mice; Animals; Acyclovir; Reinfection; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Meliaceae; Genitalia
PubMed: 37338788
DOI: 10.1007/s42770-023-01027-w -
Antiviral Research Jul 2023Genital herpes, most frequently caused by herpes simplex virus 2 (HSV-2) infection, is one of the most prevalent sexually transmitted infections. The current rationale...
Genital herpes, most frequently caused by herpes simplex virus 2 (HSV-2) infection, is one of the most prevalent sexually transmitted infections. The current rationale for the treatment of HSV-2 infection involves nucleoside analogs (e.g. acyclovir) to suppress reactivation. Enzymatic oxysterols are endogenous 27-carbon atoms molecules produced by enzymatic cholesterol oxidation, and recently emerged as a broad-spectrum host targeting antivirals. In this study, we screened selected members of an in-house synthesized library of oxysterol analogs for their activity against HSV-2, identifying three compounds, named PFM064, PFM067, and PFM069, endowed with 50% effective concentrations (EC) in the micromolar range, without exerting any apparent cytotoxicity. Moreover, the results obtained showed the ability of the novel derivatives to inhibit both cell-to-cell fusion induced by HSV-2, and the production of an intracellular viral progeny. Further experiments performed with PFM067 (which was selected for more-in-depth studies as the most effective synthetic analog) showed that these molecules act in a late stage of HSV-2 replicative cycle, by sequestering viral glycoproteins in the Golgi compartment, and likely inhibiting the nuclear egress of neo-synthetized viral capsids. Taken together, these results point to PFM067 as a promising chemical scaffold for the development of novel herpetic antivirals.
Topics: Humans; Herpesvirus 2, Human; Virus Replication; Oxysterols; Herpes Simplex; Antiviral Agents
PubMed: 37164189
DOI: 10.1016/j.antiviral.2023.105634 -
Cureus Aug 2023Herpes simplex virus (HSV) belongs to the family and is divided into two subtypes: HSV-1 and HSV-2. It is known that herpesviruses lie dormant in neural ganglion cells... (Review)
Review
Herpes simplex virus (HSV) belongs to the family and is divided into two subtypes: HSV-1 and HSV-2. It is known that herpesviruses lie dormant in neural ganglion cells and are reactivated during times of stress, trauma, fever, and immunosuppression. While HSV primarily causes mucosal infections such as cold sores or upper respiratory tract manifestations, it can also lead to serious, life-threatening infections, particularly in immunocompromised patients. Although HSV is occasionally detected in airway samples from critically ill patients, true HSV pneumonia is rare. HSV pneumonia is thought to result from the aspiration of salivary secretions that can travel from the pharynx and tracheobronchial areas to the lungs. It can be difficult to diagnose, and the presence of HSV in respiratory specimens does not necessarily indicate true infection. Treatment with antiviral drugs such as acyclovir should be considered based on the clinical presentation, corroborative findings, and the presence of cytopathological changes in the bronchoalveolar specimen. The prognosis of HSV pneumonia is generally poor and early detection is critical for better outcomes. This review discusses the risk factors, clinical presentation, diagnosis, treatment, and prognosis of HSV pneumonia and emphasizes the importance of distinguishing between true infection and carrier status.
PubMed: 37692679
DOI: 10.7759/cureus.43224 -
Microorganisms Nov 2023Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number... (Review)
Review
Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number of publications on EBV encephalitis mainly document isolated clinical cases. This study aimed to summarize published data on EBV encephalitis. A systematic literature search identified 97 EBV encephalitis cases. In the selected cases, EBV-related neurological disorders manifested as lymphocytic pleocytosis in the cerebrospinal fluid (CSF) with moderate hyperproteinorachia. The EBV PCR test was positive in 87% of the CSF samples, with wide-ranging viral loads. When encephalitis occurred in the context of past EBV infections, all of the EBV PCR tests on CSF samples were positive. On the contrary, negative EBV PCR tests on CSF samples occurred only in the context of primary infections. EBV PCR was rarely carried out on blood samples, contributing minimally to the diagnosis. For the treatment of EBV encephalitis, Aciclovir was used alone in 29% of cases, and in association with other drugs in 40% of cases. Ganciclovir (30%), corticoids (52%), and immunoglobulins (15%) were mainly used in association with other drugs. Cerebral imaging was abnormal in 69% of cases, mostly in the cerebellum and basal ganglia. This work highlights that the EBV PCR test on CSF samples is currently the main laboratory diagnostic test to diagnose EBV encephalitis. This diagnostic test is useful; however, it is imperfect. New complementary diagnostic tools, approved treatments, and standardized practices could improve patient management.
PubMed: 38137968
DOI: 10.3390/microorganisms11122825 -
International Journal of Molecular... Feb 2024Acyclovir and ganciclovir comprise the prophylaxis and treatment of herpesvirus and cytomegalovirus infections occurring in immunocompromised patients. Their therapeutic...
Acyclovir and ganciclovir comprise the prophylaxis and treatment of herpesvirus and cytomegalovirus infections occurring in immunocompromised patients. Their therapeutic drug monitoring is fundamental because of interindividual variability leading to side effects and drug resistance and is performed through several techniques, such as liquid chromatography coupled with UV spectrophotometry (HPLC-UV) or mass spectrometry (LC-MS/MS). Therefore, we developed and validated a low-cost, non-time-consuming, and low-sample-consuming HPLC-UV method. Briefly, 100 µL of sample was used for sample preparation, mainly consisting of precipitation through organic solvent. In total, 20 µL was injected into the instrument. Chromatographic separation was obtained eluting mobile phases A (10 mM ammonium formiate 0.01% formic acid) and B (acetonitrile) on a Poroshell 120 SB-C8 2.1 × 150 mm, 2.7 µm for 12 min isocratically (97:3; A:B) at a flow rate of 0.2 mL/min. The linearity range (0.5-40 mg/L) of the method allowed us to quantify both the Cmin and Cmax of acyclovir and ganciclovir. Plasma concentrations measured on a small cohort of patients undergoing acyclovir (31) and ganciclovir (9) treatment by the proposed method and the LC-MS/MS methods, already in use, were significantly correlated. The proposed HPLC-UV method may be implemented in diagnostics as an alternative method in case of the unavailability of the LC-MS/MS system.
Topics: Humans; Child; Acyclovir; Ganciclovir; Chromatography, High Pressure Liquid; Chromatography, Liquid; Tandem Mass Spectrometry; Sensitivity and Specificity; Reproducibility of Results
PubMed: 38473930
DOI: 10.3390/ijms25052685 -
Archives of Dermatological Research Jun 2024Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases.
Topics: Humans; Warts; Injections, Intralesional; Acyclovir; Male; Female; Adult; Antiviral Agents; Treatment Outcome; Young Adult; Hepatitis B Vaccines; Adolescent; Middle Aged
PubMed: 38822848
DOI: 10.1007/s00403-024-03001-4 -
Infection Aug 2023Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older... (Observational Study)
Observational Study
PURPOSE
Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years.
METHODS
We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years.
RESULTS
Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥ 65 years, including 74 (15%) ≥ 80 years. Patients ≥ 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm[13-220] in 65-79 years, 62 [17-180] in ≥ 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥ 80 years (P < 0.001). Age ≥ 80 years, coma on admission, CSF protein ≥ 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality.
CONCLUSION
Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.
Topics: Adult; Humans; Aged; Aged, 80 and over; Prospective Studies; Coma; Infectious Encephalitis; Encephalitis; Acyclovir; France; Herpesvirus 3, Human
PubMed: 36152225
DOI: 10.1007/s15010-022-01927-3 -
American Journal of Translational... 2023To explore the application value of intravenous acyclovir in children with infectious mononucleosis (IM) and its effects on immune function.
OBJECTIVE
To explore the application value of intravenous acyclovir in children with infectious mononucleosis (IM) and its effects on immune function.
METHODS
The data of 136 children with IM treated in Anhui Provincial Children's Hospital from March 2019 to March 2022 were retrospectively analyzed. According to the inclusion and exclusion criteria, 98 children were selected. Among them, 45 children treated with routine ribavirin were assigned to the control group, and the other 53 children treated with intravenous acyclovir were enrolled into the observation group. The two groups were compared in terms of efficacy, incidence of adverse reactions, recovery time of clinical symptoms, and immune function indexes, IgG, IgA, IgM, white blood cell (WBC) count and lymphocyte proportion, before and 10 days after the treatment. Independent risk factors affecting efficacy were analyzed by multivariate logistic regression analysis.
RESULTS
The observation group showed a significantly higher overall response rate than the control group (P=0.025). The control group experienced significantly longer recovery time of body temperature returning to normal, cure time of isthmitis, time for lymph node reduction, and alleviation time of hepatomegaly than the observation group (P<0.05). Additionally, the control group presented with a significantly higher incidence of adverse reactions than the observation group (P=0.028). After treatment, the observation group showed significantly lower levels of IgG, IgA, IgM, WBC count and lymphocyte proportion than the control group (all P<0.010). Longer average course of disease (OR: 1.449, 95% CI: 1.095-1.918), higher admission temperature (OR: 6.996, 95% CI: 1.350-36.257), higher admission IgA level (OR: 4.735, 95% CI: 1.357-16.520) and higher admission IgG level (OR: 1.470, 95% CI: 1.012-2.134) were independent risk factors for ineffective efficacy, while acyclovir (OR: 0.058, 95% CI: 0.005-0.729) was an independent protective factor.
CONCLUSION
In the treatment of IM, intravenous acyclovir can substantially improve the overall clinical response rate for patients, with less adverse reactions, and can greatly alleviate various clinical symptoms and signs including fever, isthmitis, cervical lymph node enlargement, and hepatosplenomegaly, with obvious regulating effects on the immune function, so it is worth popularizing and applying in clinical practice.
PubMed: 37692931
DOI: No ID Found -
Journal of Ayurveda and Integrative... 2023Herpes simplex virus type-1 and type-2 cause a viral disease named Herpes. Genital herpes is mainly caused by HSV-2 with symptoms of painful and itchy blisters on the... (Review)
Review
BACKGROUND
Herpes simplex virus type-1 and type-2 cause a viral disease named Herpes. Genital herpes is mainly caused by HSV-2 with symptoms of painful and itchy blisters on the vagina, cervix, buttocks, anus, penis, or inner thighs with blisters that rupture and convert into sores. The homeopathic remedy Rhus Tox has been widely used to treat herpes and has shown invitro anti-inflammatory effects in previous studies.
PURPOSE
The presented review focuses on relapses and harmful effects caused by acyclovir in modern medicine and the probable antiherpetic activity of Rhus Tox on HSV infection based on its pathophysiology, preclinical findings, on primary cultured mouse chondrocytes, mouse cell line MC3T3e1 and a comparative study of Natrum Mur with Rhus Tox on HSV infection.
STUDY DESIGN
The design of the study focuses mainly on the descriptive data available in various literature articles.
METHOD
Databases such as PubMed, Google Scholar, Medline and ScienceDirect were used to search the articles. Articles are selected from 1994 to 2022 focusing solely on the competence of Rhus Tox against herpes. Keywords used for the study are antiviral, Herpes, Rhus Tox, in vitro and homeopathy.
RESULTS
The review includes fifteen articles, including 4 full-text articles on HSV, 6 in vitro studies of homeopathic compounds performed on the herpes virus, and 5 articles based on the pathophysiology and effects of Rhus tox. The review article proposes the anti-inflammatory and antiviral action of the homeopathic remedy Rhus Tox which can be used in crisis conditions when the physician doubts the simillimum, as it prevents further outbreaks of HSV infection.
CONCLUSION
The homeopathic medicine Rhus Tox has no cytotoxicity observed under in vitro conditions and can be used to treat herpes infection. Further studies are needed to confirm the results under in vitro and in vivo conditions as well as in clinical trials.
PubMed: 37421729
DOI: 10.1016/j.jaim.2023.100739 -
European Journal of Pharmaceutics and... Dec 2023Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in...
Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in vitro is limited and multiple simulated intestinal fluid recipes have been developed but with no consensus which is optimal. This study has utilised nine bioequivalent simulated fed intestinal media recipes that cover over 90% of the compositional variability of sampled fed human intestinal fluid. The solubility of 24 drugs (Acidic; furosemide, ibuprofen, indomethacin, mefenamic acid, naproxen, phenytoin, piroxicam, valsartan, zafirlukast: Basic; aprepitant, atazanavir, bromocriptine, carvedilol, dipyridamole, posaconazole, tadalafil: Neutral; acyclovir, carbamazepine, felodipine, fenofibrate, griseofulvin, itraconazole, paracetamol, probucol) has been assessed to determine if structured solubility behaviour is present. The measured solubility behaviour can be split into four categories and is consistent with drug physicochemical properties and previous solubility studies. For acidic drugs (category 1) solubility is controlled by media pH and the lowest and highest pH media identify the lowest and highest solubility in 90% of cases. For weakly acidic, basic and neutral drugs (category 2) solubility is controlled by media pH and total amphiphile concentration (TAC), a consistent solubility pattern is evident with variation related to individual drug media component interactions. The lowest and highest pH × TAC media identify the lowest and highest solubility in 70% and 90% of cases respectively. Four drugs, which are non-ionised in the media systems (category 3), have been identified with a very narrow solubility range, indicating minimal impact of the simulated media on solubility. Three drugs exhibit solubility behaviour that is not consistent with the remainder (category 4). The results indicate that the use of two bioequivalent fed intestinal media from the original nine will identify in vitro the maximum and minimum solubility values for the majority of drugs and due to the media derivation this is probably applicable in vivo. When combined with a previous fasted study, this introduces interesting possibilities to measure a solubility range in vitro that can provide Quality by Design based decisions to rationalise drug and formulation development. Overall this indicates that the multi-dimensional media system is worthy of further investigation as in vitro tool to assess fed intestinal solubility.
Topics: Humans; Solubility; Hydrogen-Ion Concentration; Intestines; Pharmaceutical Preparations; Indomethacin; Intestinal Absorption
PubMed: 37890541
DOI: 10.1016/j.ejpb.2023.10.017