Combining different drugs synergistically is an essential aspect of developing effective treatments. Although there is a plethora of research on computational prediction for new combination therapies, there is limited to no research on combination therapies in the treatment of viral diseases. This paper proposes AI-based models for predicting novel antiviral combinations to treat virus diseases synergistically. To do this, we assembled a comprehensive dataset comprising information on viral strains, drug compounds, and their known interactions. As far as we know, this is the first dataset and learning model on combination therapy for viruses. Our proposal includes using a random forest model, an SVM model, and a deep model to train viral combination therapy. The machine learning models showed the highest performance, and the predicted values were validated by a t-test, indicating the effectiveness of the proposed methods. One of the predicted combinations of acyclovir and ribavirin has been experimentally confirmed to have a synergistic antiviral effect against herpes simplex type-1 virus, as described in the literature.

Measles is a highly contagious but vaccine-preventable airborne-transmitted viral infection for which there has been a recent resurgence of cases worldwide over the past year, including in countries such as the United Kingdom (UK) which had previously successfully achieved endemic measles elimination through vaccination programs. Measles is typically a self-limiting illness, but can rarely cause severe, life-threatening disease, particularly when complicated by respiratory or neurological involvement. These severe complications are not typically seen in the absence of immunosuppression. We describe a rare case of severe measles with pneumonitis in an immunocompetent adult necessitating admission to an intensive care unit (ICU).

BACKGROUND: Respiratory syncytial virus (RSV) is a single-stranded RNA virus that commonly causes symptoms of upper respiratory tract infections in humans, with a clear seasonal trend. However, in immunocompromised and elderly patients, RSV infections still result in high rates of hospitalization and even risk of death.
METHODS: We report a case of RSV infection in an adult with immunodeficiency, which initially showed only mild symptoms of upper respiratory tract infection, which did not improve after receiving empirical anti-infective treatment, and the foci of infection in the lungs continued to expand, which led to the aggravation of the disease. The diagnosis of RSV infection was finally confirmed by electron bronchoscopy and pathogenetic examination of the bronchoalveolar lavage fluid. The patient was given intravenous ribavirin treatment for one week. After one week of intravenous ribavirin treatment, the patient\'s symptoms improved significantly. A repeat chest CT suggested that the lung lesions were smaller than before. In order to improve clinicians\' awareness of this disease, we jointly conducted a literature analysis.
RESULTS: The final diagnosis of RSV was made by analyzing the patient\'s history, symptoms, and signs and performing relevant examinations.
CONCLUSIONS: For patients with poor results of empirical application of antibiotics, electronic bronchoscopy and pathogenetic examination should be carried out at an early stage to clarify the nature of the lesions and to avoid rapid deterioration of the condition leading to life-threatening conditions in the patients. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and appropriate treatment should be given at an early stage.

UNASSIGNED: Therapeutic drug monitoring (TDM) can be a useful tool in the clinical management of anti-hepatitis C virus (anti-HCV) drugs. Methods for the determination of various types of anti-HCV drugs in biological samples are, therefore, needed for clinical laboratories.
UNASSIGNED: In this work, employing the LC-MS/MS approach, we aimed to develop a multiplexed method for identification of the following anti-HCV drugs: Ribavirin (RBV), Boceprevir (BOC), Telaprevir (TVR), Simeprevir (SIM), Daclatasvir (DAC), Sofosbuvir (SOF) and its metabolite GS 331007 (SOFM) in liquid plasma and in dried plasma spots (DPSs).
UNASSIGNED: A single-step extractive-deproteinization was employed for both liquid plasma and DPSs. Reverse-phase liquid chromatography coupled with MRM detection was developed for multiplexed drug detection and quantification.
UNASSIGNED: Sensitivities (expressed as LOQ) were 10 (±1.2), 10 (±4.9), 10 (±4.4), 10 (±4.4), 10 (±6.4), 10 (±3.4), 10 (±6.4) ng/ml for RBV, SOFM, SOF, DAC, BOC, TVR, and SIM, respectively; accuracy (expressed as BIAS%) was <10% for all drugs; reproducibility (intra- and inter-day CV%) was <10% for all drugs; dynamic range was 10-10,000 ng/ml for all drugs.
UNASSIGNED: A novel, simple, rapid and robust LC-MS/MS multiplex assay for the TDM of various anti-HCV drugs that are currently in the clinic was successfully developed. Application to DPS samples enabled TDM to be used for outpatients as well.

Reproductive toxicity is one of the major concerns in drug development. Thus, we have developed its screening system using Caenorhabditis elegans, which has a life cycle of three days and similar coding genes as humans. Antiviral nucleoside analogs used for acute infections are known to cause reproductive toxicity, contraindicated for pregnant women, and are used for comparing their reproductive toxicity in C. elegans and experimental animals. None of the drug treatments affected the number of offspring and the concentrations without toxicity to nematodes were consistent with no cytotoxicity or toxicity in experimental animals or humans. Favipiravir, ribavirin, molnupiravir (NHC), acyclovir, ganciclovir, zidovudine, and thalidomide significantly increased the incidence of arrested embryos but amenamevir, letermovir, and guanosine did not. RNA-dependent RNA polymerase (RdRp) inhibitors, in the order of favipiravir, ribavirin, and NHC increased the incidence of arrested embryos, possibly due to the specificity of favipiravir for RdRp and less cytotoxicity. RdRp inhibitors would impair RNA interference through RdRp expressed by telomerase reverse transcriptase during embryogenesis and cause embryo-fetal toxicity. The incidence of arrested embryos may be affected by differences in the substrate specificity of DNA polymerases and metabolism between C. elegans, animals, and humans. The concordance between the results of the screening system for reproductive toxicity of antivirals in C. elegans and those in experimental animals based on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, reproductive toxicology confirms its appropriateness as a screening system for reproductive toxicity. Favipiravir and zidovudine were the least toxic to C. e legans among the antiviral drugs examined.

OBJECTIVE: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles.
METHODS: We evaluated the TS for the treatment of hepatitis C (HCV) in an international cohort of patients treated with direct-acting antivirals between 2015 and 2020. The primary outcome was the number of patients receiving one of the two preferred treatment options of the HCV TS, based on the highest level of evidence, cure rate, absence of ribavirin-associated adverse effects, and treatment duration.
RESULTS: We enrolled 567 patients. The number of patients treated with one of the two preferred treatment options according to the HCV TS ranged between 27% (2015) and 60% (2020; p < 0.001). Most of the patients received a regimen with a longer treatment-duration (up to 34%) and/or addition of ribavirin (up to 14%). The effect on the expected cure-rate was minimal (1-6% higher) when the first preferred TherapySelector option was given compared to the actual treatment.
CONCLUSIONS: Medical decision-making can be optimised by a guideline add-on; in HCV its use appears to minimise adverse effects and cost. The use of such an add-on might have a greater impact in diseases with suboptimal cure-rates, high costs or adverse effects, for which treatment options rely on specific patient characteristics.

UNASSIGNED: This study aimed to assess the overall treatment response of Genotype-3 Chronic HCV Pakistani Patients with or without cirrhosis to Ledipasvir plus Sofosbuvir combination.
UNASSIGNED: In this observational study, HCV Genotype-3 patients were enrolled from Liver Center, DHQ Hospital, Faisalabad and divided into two groups, i.e., non-cirrhotic and compensated cirrhotic patients. The study spanned for a period of 24 months (November 2019 - November 2021) from the first enrollment to the last follow up. Non-cirrhotic patients received Ledipasvir/Sofosbuvir (LDV/SOF) 90/400mg for 12 weeks and cirrhotic patients received LDV/SOF with Ribavirin (RBV) for 12 weeks and without RBV for 24 weeks. The treatment efficacy in terms of sustained virological response (SVR12) was monitored 12 weeks post-treatment. The safety profile, and health-related quality of life (HRQoL) were monitored from baseline to follow-up visits.
UNASSIGNED: Two hundred and ninety out of 309 (93.85%) non-cirrhotic and 31 out of 33 (93.94%) compensated cirrhotic patients achieved SVR-12. The safety profile of the non-cirrhotic and compensated cirrhotic patients was comparable throughout the study duration. Fatigue was the most commonly reported adverse event (AE) in non-cirrhotic and compensated cirrhotic patients, followed by headache, nausea, and fever. The HRQoL improved from baseline to follow-up visits among patients of both groups.
UNASSIGNED: It is concluded that LDV and SOF combination regimen is safe and effective for treating Genotype-3 HCV patients without cirrhosis/compensated cirrhosis, and also improves the patient\'s HRQoL.

Rabies is a fatal neurological disorder caused by rabies virus (RABV) infection. Approximately 60,000 patients die from rabies annually, and there are no effective treatments for this disease. Nucleoside analogs are employed as antiviral drugs based on their broad antiviral spectrum, and certain nucleoside analogs have been reported to exhibit anti-RABV activity. The nucleoside analog β-d-N4-hydroxycytidine (NHC) has antiviral effects against a range of RNA viruses. Molnupiravir (MPV), a prodrug of NHC, is clinically used as an oral antiviral drug for coronavirus infections. Despite its broad-spectrum activity, the antiviral activity of NHC against RABV remains unclear. In this study, we reveal that NHC exhibits comparable in vitro anti-RABV activity as ribavirin and favipiravir (also known as T-705) with a 90% effective concentration of 6 μM in mouse neuroblastoma cells. NHC reduced viral loads in neuronal and nonneuronal cells in a dose-dependent manner. Both laboratory and field RABVs (fixed and street strains, respectively) were susceptible to NHC. However, no increase in survival or reduction in viral titers in the brain was observed in RABV-infected mice treated prophylactically with MPV. These findings highlight the potential and challenges of NHC in the treatment of RABV infection.

α-Synuclein (α-syn) is an intrinsically disordered protein, linked genetically and neuropathologically to Parkinson\'s disease where this protein aggregates within the brain. Hence, identifying compounds capable of impeding α-syn aggregation puts forward a promising approach for the development of disease-modifying therapies. Herein, we investigated the efficacy of Ribavirin, an FDA-approved compound, in curtailing α-syn amyloid transformation, employing an array of bioinformatic tools and systematic analysis using biophysical techniques. Ribavirin shows a dose dependent anti-aggregation propensity where it effectively subdued the formation of mature fibrillar aggregates of α-syn, where even at the lowest concentration there was a 69 % reduction in the ThT maxima. Ribavirin averts the formation of mature fibrillar aggregates by interacting with the NAC domain of α-syn. Ribavirin redirects the amyloid transformation of α-syn by emanating aggregates of lower order with reduced cross β-sheet signature and revokes the formation of on-pathway amyloids. Collectively, our study puts forward the novel potency of Ribavirin as a promising molecule for therapeutic intervention in Parkinson\'s disease.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/RACV) in Vero E6 cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(β-D-ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β-D-ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased.