Search Results (146)

During the current outbreak of Marburg virus disease (MVD) in Rwanda, we synthesized evidence from the literature to improve case management. Accordingly, experimental treatment was offered to patients under close follow-up. Remdesivir alone or in combination with monoclonal antibody treatment (MBP091) complemented with supportive care has improved the clinical outcomes of patients. Additionally, we have identified several experimental therapies currently under investigation, including antiviral drugs such as favipiravir, galidesivir, obeldesivir, and remdesivir, along with monoclonal and polyclonal antibodies (e.g., polyclonal IgG, monoclonal antibody MR-78-N; MR82-N; MR191-N; monoclonal antibodies MR186-YTE and MBP091). Furthermore, substantial progress is being made in vaccine development, with promising candidates including adenovirus-vectored vaccines, DNA vaccines, and the recombinant vesicular stomatitis virus (rVSV) vaccine. Moreover, innovative preventive and treatment strategies—such as synthetic hormones like estradiol benzoate, small interfering RNA (siRNA), interferon-β therapy, and phosphorodiamidate morpholino oligomers—are emerging as potential options for MVD management. Further investment is needed to accelerate research and optimize these therapeutics and preventive modalities. Additional epidemiological, preclinical, and clinical studies are warranted to generate the evidence required to inform policymaking, resource mobilization, and the implementation of cost-effective interventions for the prevention, control, and treatment of MVD. Full article

The presence of pharmaceuticals in wastewater raises concerns about the toxicological risks associated with its discharge and reuse. During the COVID-19 pandemic, widespread use of antivirals (ATVs), along with plastic gloves and masks, further contributed to pharmaceuticals in wastewater. Chlorination, commonly used for wastewater disinfection, may alter the toxicity of antivirals in the presence of microplastics (MPs) and complex organics in secondarily treated wastewater. To investigate this, synthetic secondary effluent containing Favipiravir (FAV) and Oseltamivir (OSE) was exposed to various chlorination conditions, both with and without MPs. The changes in the concentrations of FAV and OSE were measured using LC-MS/MS with isotopically labeled standards. Chlorination was more effective in removing Favipiravir (42 ± 4%) than Oseltamivir (26 ± 3%). The ecotoxicological effects were assessed on two species—Aliivibrio fischeri (a bacterium) and Enchytraeus crypticus (a soil invertebrate)—to evaluate potential impacts on aquatic and soil environments, though discharge of or irrigation with treated wastewater, respectively. Results indicated that chlorination of wastewater itself increased toxicity more significantly than the chlorination of antivirals to either species, suggesting that chlorination may not be as beneficial despite its cost-effectiveness. The effects of MPs in chlorinated wastewater on toxicity highlighted the importance of sample matrices in environmental toxicity studies. Full article

Ribavirin, 1-(β-D-Ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide, which is included in the list of drugs recommended in the guidelines for the diagnosis and treatment of SARS-CoV-2 infection, has been the subject of experimental and theoretical investigation. The most thermodynamically stable polymorphic form was studied using ¹H-¹⁴N NQR cross-relaxation, periodic DFT/QTAIM/RDS/3D Hirshfeld surfaces, and molecular docking. For the first time, a ¹H-¹⁴N cross-relaxation spectrum of ribavirin was recorded and interpreted. Twelve resonance frequencies were assigned to four inequivalent nitrogen positions in the molecule using combined experimental techniques and solid-state quantum chemical calculations. The influence of the structural alteration on the NQR parameters was modeled using GGA/RPBE. The differences in the binding pattern of ribavirin, acadesine, inosine, guanosine, and favipiravir-ribofuranosyl in the solid state and the protein-ligand complex were assessed to elucidate the differences in the binding mechanism at the molecular level due to aglycone modification. The replacement of the carbon adjacent to the ribose with nitrogen, in conjunction with the absence of oxygen at the 2-position of the ring, resulted in an increased flexibility of the RBV structure in comparison to the favipiravir-ribofuranosyl structure. The present study identified the intramolecular hydrogen bond NH···N in RBV as playing a crucial role in the formation of a quasi-five-membered ring. However, this bond was proven to be too weak to force positioning of the amide group in the ring plane. The ribofuranosyl in RBV inhibits tautomerism and freezes the conformation of the amide group. The results of the molecular dynamics simulations demonstrated that RBV and favipiravir-ribofuranosyl incorporated into the RNA primer exhibited comparable stability within the protein binding region. The titular anti-butterfly (inverted butterfly) effect is associated with the consequences of both the changes in aglycone moiety and the neighborhood alteration. Seven structure-binding strength indices and six novel quadrupolar indices defined in this study have been proven to facilitate the evaluation of the similarity of binding motifs in the solid state and protein-ligand complex. Full article

The Ebola virus (EBOV), a highly lethal pathogen causing hemorrhagic fever, poses a persistent public health threat, with devastating multi-organ complications and high transmission potential through bodily fluids. EBOV’s pathogenesis is marked by severe oxidative stress and immune dysregulation, where increased reactive oxygen species (ROS) levels foster cellular damage, hinder immune defenses, and facilitate viral replication. Through immune evasion and suppression of cellular stress responses, EBOV affects both innate and adaptive immunity, activating pyroptosis, PANoptosis, necroptosis, and lymphocyte apoptosis, thereby amplifying inflammation and disease severity. Recent research suggests that bioactive molecules, including quercetin, curcumin, eugenol, and p-anisaldehyde, may offer therapeutic potential due to their antioxidant, anti-inflammatory, and immunomodulatory effects. This review also underscores the potential of conventional treatments, including amiodarone, favipiravir, remdesivir, azithromycin, chloroquine, and nitazoxanide, as therapeutic agents against EBOV, thanks to their antiviral and anti-inflammatory properties, although their efficacy varies across experimental models. These natural compounds could enhance immune resilience by scavenging ROS, modulating inflammation, and mitigating immune dysregulation, presenting promising adjunctive strategies to support conventional EBOV therapies. Full article

Canine distemper is a severe and lethal viral disease of dogs and wild carnivores with an urgent need for the identification of effective antiviral agents against canine distemper virus (CDV). We assessed multiple agents for their ability to block the replication of three different lineages of CDV isolated from wild carnivores in the United States. Six antiviral compounds were selected after preliminary experiments that excluded ribavirin, hesperidin and rutin: a protease inhibitor (nirmatrelvir), a polymerase inhibitor (favipiravir) and four nucleoside analogs (remdesivir, GS-441524, EIDD2801 and EIDD1931). Antiviral efficacy was determined by the attenuation of the cytopathic effect in a CDV-susceptible cell line and the inhibition of viral RNA replication. The nucleoside analog GS-441524 effectively blocked the replication of CDV at pharmacologically relevant concentrations. Four other antiviral agents inhibited CDV replication to a lesser degree (remdesivir, nirmatrelvir, EIDD2801 and EIDD1931). The replication of different viral lineages was differentially inhibited by the antivirals. Several of the nucleoside analogs have been safely used previously in carnivore species for the treatment of other viral diseases, suggesting that they may be promising candidates for the treatment of canine distemper in dogs. Our results emphasize the need to consider different viral lineages in the screening of antiviral compounds. Full article

Every year, dengue virus affects hundreds of millions of individuals worldwide. To date, there is no specific medication to treat dengue virus infections. Nucleobases, the base of a nucleoside without ribose, are understudied as potential treatments for viral infections. Antiviral nucleobases are converted in infected cells to their corresponding nucleoside triphosphate active form. Importantly, the conversion of nucleobases to their active nucleotide form and their antiviral effect can be enhanced when combined with de novo nucleotide biosynthesis inhibitors. In this work, we evaluated seven purine and pyrimidine nucleobases alone or combined with six purine or pyrimidine de novo nucleotide biosynthesis inhibitors, including novel prodrugs. Our study revealed that while a strong potentiation of purine nucleobases by purine de novo nucleotide biosynthesis inhibitors was observed, the pyrimidine nucleobases were not potentiated by pyrimidine de novo nucleotide biosynthesis inhibitors, possibly highlighting a significant difference between the modulation of purine versus pyrimidine de novo pathways and their impact on nucleobase potentiation. Most significant antiviral effects and potentiation were observed for Favipiravir, T-1105, and ribavirin nucleobases combined with purine nucleotide de novo synthesis inhibitors. These results are significant because drug combinations may solve the limited efficacy observed for some antiviral nucleobase drugs such as Favipiravir. Full article

Background: Coronaviruses, including SARS-CoV-2, cause a range of respiratory and gastrointestinal illnesses, with COVID-19 becoming a global pandemic in 2020. Favipiravir, an antiviral drug, has shown promising results in reducing disease progression and improving recovery in COVID-19 patients. Methodology: This retrospective cohort study evaluated the efficacy, safety, and clinical outcomes of favipiravir in COVID-19 pneumonia patients admitted to the AFHSR. The analysis included patient characteristics, treatment responses, and laboratory parameters. Data were cleaned using Excel and analyzed with IBM SPSS version 29.0.0. Results: Our study included 297 COVID-19 pneumonia patients treated with favipiravir, with 129 (43.4%) females and 165 (55.6%) males with a mean age of 61.47 years. Comorbidities were present in 223 patients (75.1%), most commonly diabetes (N = 78, 33.6%) and hypertension (N = 72, 31.0%). Common symptoms were shortness of breath (N = 92, 31.0%), a cough (N = 86, 29.0%), and fever (N = 69, 23.3%). Complications occurred in 53 patients (17.8%), with acute kidney injury in 15 patients (5.1%). The overall mortality was 62 (20.9%), higher in those with comorbidities (75.7%, p = 0.017). Kaplan–Meier analysis showed worse survival for patients with comorbidities (p = 0.049) and smokers (p = 0.042). Elevated WBCs, LDH, AST, and CRP were linked to better survival (p < 0.05). Non-survivors had more severe respiratory impairment (FiO₂, p = 0.035). Conclusions: Our study suggests favipiravir may help reduce ICU admissions and mortality in COVID-19 pneumonia patients, but outcomes are significantly influenced by age, comorbidities, and complications. This highlights the need for individualized treatment strategies. Further randomized controlled trials are essential to define favipiravir’s role in COVID-19 management. Full article

Favipiravir (FVP) and remdesivir (RDV) have demonstrable antiviral activity against SARS-CoV-2. Here, the efficacy of FVP, RDV, and FVP with RDV (FVP + RDV) in combination was assessed in Syrian golden hamsters challenged with SARS-CoV- 2 (B.1.1.7) following intraperitoneal administration. At day 4 post infection, viral RNA and viral antigen expression were significantly lower in lungs for all three treatment groups compared to the sham treatment. Similarly, viral titres in the lungs were lower in all treatment groups compared to the sham treatment. The FVP + RDV combination was the only treatment group where viral RNA in nasal turbinate and lung, virus titres in lung, and viral antigen expression (lung) were all lower than those for the sham treatment group. Moreover, lower viral titre values were observed in the FVP + RDV group compared to other treatment groups, albeit only significantly lower in comparison to those in the RDV-only-treated group. Further assessment of the potential utility of FVP in combination with RDV may be warranted. Future studies should also consider whether the combination of these two drugs may reduce the speed at which drug resistance mutations are selected. Full article

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection. Full article

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has posed significant health challenges worldwide. While children generally experience less severe illness compared to adults, pneumonia remains a substantial risk, particularly for those under five years old. This study examines the clinical characteristics and treatment outcomes of pediatric COVID-19 pneumonia patients treated with favipiravir in Thailand, aiming to identify associated factors for pneumonia. A retrospective review was performed on pediatric patients aged 1 month to 18 years hospitalized with COVID-19 at Srinagarind Hospital, Khon Kaen University, from 13 January 2020 to 15 November 2021. Data on demographics, clinical symptoms, treatment, and outcomes were collected, and logistic regression analysis was used to identify factors associated with pneumonia. Among 349 hospitalized children, the median age was 8 years, with 51.9% being male. Symptoms included a fever (100%), a cough (74.2%), and a rash (24.9%). COVID-19 pneumonia was diagnosed in 54.7% of the children. Favipiravir was administered as the standard treatment, showing mild adverse effects, including a rash (4.3%) and nausea (2.8%). Monocytosis was significantly associated with COVID-19 pneumonia (aOR 30.85, 95% CI: 9.03–105.41, p < 0.001), with an ROC curve area of 0.77 (95% CI: 0.71–0.83). Pediatric COVID-19 patients typically exhibit mild-to-moderate symptoms, with pneumonia being common in the early pandemic phase. Monocytosis is a significant factor associated with COVID-19 pneumonia. Favipiravir demonstrated mild adverse effects. Further studies are needed to validate these findings across different settings and phases of the pandemic. Full article

Favipiravir (FP) and ebselen (EB) belong to a diverse class of antiviral drugs known for their significant efficacy in treating various viral infections. Utilizing molecular dynamics (MD) simulations, machine learning, and van der Waals density functional theory, we accurately elucidate the binding properties of these antiviral drugs on a phosphorene single-layer. To further investigate these characteristics, this study employs four distinct machine learning models—Random Forest, Gradient Boosting, XGBoost, and CatBoost. The Hamiltonian of antiviral molecules within a monolayer of phosphorene is appropriately trained. The key aspect of utilizing machine learning (ML) in drug design revolves around training models that are efficient and precise in approximating density functional theory (DFT). Furthermore, the study employs SHAP (SHapley Additive exPlanations) to elucidate model predictions, providing insights into the contribution of each feature. To explore the interaction characteristics and thermodynamic properties of the hybrid drug, we employ molecular dynamics and DFT calculations in a vacuum interface. Our findings suggest that this functionalized 2D complex exhibits robust thermostability, indicating its potential as an effective and enabled entity. The observed variations in free energy at different surface charges and temperatures suggest the adsorption potential of FP and EB molecules from the surrounding environment. Full article

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo. Full article

In this work, we conducted a study of the interaction between DNA and favipiravir (FAV). This chemotherapeutic compound is an antiviral drug for the treatment of COVID-19 and other infections caused by RNA viruses. This paper examines the electroanalytical characteristics of FAV. The determined concentrations correspond to therapeutically significant ones in the range of 50–500 µM (R² = 0.943). We have shown that FAV can be electro-oxidized around the potential of +0.96 V ÷ +0.98 V (vs. Ag/AgCl). A mechanism for electrochemical oxidation of FAV was proposed. The effect of the drug on DNA was recorded as changes in the intensity of electrochemical oxidation of heterocyclic nucleobases (guanine, adenine and thymine) using screen-printed graphite electrodes modified with single-walled carbon nanotubes and titanium oxide nanoparticles. In this work, the binding constants (Kb) of FAV/dsDNA complexes for guanine, adenine and thymine were calculated. The values of the DNA-mediated electrochemical decline coefficient were calculated as the ratio of the intensity of signals for the electrochemical oxidation of guanine, adenine and thymine in the presence of FAV to the intensity of signals for the electro-oxidation of these bases without drug (S, %). Based on the analysis of electrochemical parameters, values of binding constants and spectral data, intercalation was proposed as the principal mechanism of the antiviral drug FAV interaction with DNA. The interaction with calf thymus DNA also confirmed the intercalation mechanism. However, an additional mode of interaction, such as a damage effect together with electrostatic interactions, was revealed in a prolonged exposure of DNA to FAV. Full article

First recognized 15 years ago, Heartland virus disease (Heartland) is a tickborne infection contracted from the transmission of Heartland virus (HRTV) through tick bites from the lone star tick (Amblyomma americanum) and potentially other tick species. Heartland symptoms include a fever <100.4 °F, lethargy, fatigue, headaches, myalgia, a loss of appetite, nausea, diarrhea, weight loss, arthralgia, leukopenia and thrombocytopenia. We reviewed the existing peer-reviewed literature for HRTV and Heartland to more completely characterize this rarely reported, recently discovered illness. The absence of ongoing serosurveys and targeted clinical and tickborne virus investigations specific to HRTV presence and Heartland likely contributes to infection underestimation. While HRTV transmission occurs in southern and midwestern states, the true range of this infection is likely larger than now understood. The disease’s proliferation benefits from an expanded tick range due to rising climate temperatures favoring habitat expansion. We recommend HRTV disease be considered in the differential diagnosis for patients with a reported exposure to ticks in areas where HRTV has been previously identified. HRTV testing should be considered early for those matching the Heartland disease profile and nonresponsive to initial broad-spectrum antimicrobial treatment. Despite aggressive supportive therapy, patients deteriorating to sepsis early in the course of the disease have a very grim prognosis. Full article