Antiviral research最新文献

Rhinovirus (RV), a common cold virus, is a predominant circulating virus which is increasingly recognized for its contribution to severe respiratory tract infections. Given the lack of vaccines, bacterial lysates are a promising alternative to prevent recurrent respiratory tract infections. OM-85, a bacterial lysate from 21 respiratory bacteria, has long been used safely as an oral drug to prevent recurrent respiratory tract infections in clinics. However, with inhalation emerging as preferred route to directly target the site of airway infection, OM-85 is being developed for local administration in the respiratory tract to enhance mucosal immunity. This study evaluated the prophylactic efficacy of intranasally administered OM-85 in a murine model of RV infection. Mice were treated over a period of 12 days prior to RV infection and the immune response and viral load were assessed. Intranasal administration of OM-85 primed the host immune response by the recruitment of innate immune cells to the lung, resulting in enhanced viral clearance. This was accompanied by a modulation of the RV-induced immune response toward a less pro-inflammatory phenotype, marked by substantial reduction of pro-inflammatory cytokines and neutrophil infiltration. The immune response was shifted towards an anti-inflammatory state supporting control of inflammation. Complementary precision-cut lung slice experiments confirmed the initial immune-priming activity of OM-85 independent of RV infection. These findings demonstrate that local administration of OM-85 in the airways effectively primes the innate immune response and confers mucosal protective effects against RV-induced respiratory tract infection.

The advent of highly effective direct-acting antivirals (DAAs) has transformed hepatitis C virus (HCV) infection into a curable disease, with cure rates exceeding 95% across viral genotypes and clinical settings. Along with simplified, short-course treatment regimens and significant advancements in diagnostic technologies, these therapeutic breakthroughs have made eliminating HCV as a public health concern, as defined by the World Health Organization, a realistic goal. However, despite this progress, global advances toward elimination have fallen short of expectations. This review examines why HCV elimination appears to be within reach yet remains elusive. First, the molecular virology of HCV and the pharmacological rationale underlying modern DAA combination therapies are summarized to highlight how complementary antiviral mechanisms and high genetic barriers to resistance enable definitive virological cure. Then, the key factors limiting the translation of individual-level cures into population-level impact are analyzed. Persistent transmission in high-risk and marginalized populations, including people who inject drugs, incarcerated individuals, and men who have sex with men, continues to drive new infections. Incomplete case identification, losses along the care cascade, reinfection in the absence of protective immunity, and the lack of a prophylactic vaccine further constrain treatment-based prevention strategies. Structural and systemic barriers, including stigma, criminalization, inequitable access to diagnostics and treatment, fragile health systems, and uneven political commitment, exacerbate these challenges, particularly in low- and middle-income countries. Eliminating HCV will require sustained political commitment, equitable scaling up of testing and treatment, integration of care into primary and community-based services, robust harm reduction interventions, and coordination.

Measles remains one of the most contagious viral infections, and its resurgence due to declining global vaccination coverage has renewed interest in therapeutic and preventive strategies. This systematic review analyzes current and emerging acute therapies and their relationship to measles virology and clinical outcomes. A systematic search of PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and Google Scholar (1990-2025) was conducted using predefined inclusion and exclusion criteria to identify clinical studies on acute measles treatment. Despite being used off-label, ribavirin and interferon-α have demonstrated reductions in severity and complications in small clinical trials and case reports. Vitamin A supplementation remains the only widely recommended therapy with strong evidence for reducing morbidity and mortality, particularly in children with deficiency. Traditional Chinese medications such as Tanreqing and Xiyanping show symptomatic improvement but require mechanistic validation. Investigational therapeutics, including polymerase inhibitors such as ERDRP-0519, monoclonal antibodies targeting the fusion protein, and antiviral candidates such as remdesivir, offer promising future options. While vaccination remains essential, adjunctive therapies provide additional tools to reduce complications in under-vaccinated populations.

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the ongoing need for effective antiviral therapies targeting this now-endemic virus. Ibuzatrelvir, a second-generation SARS-CoV-2 main protease (Mpro) inhibitor, has demonstrated potent antiviral activity without the need for a pharmacokinetic booster such as ritonavir. In the present study, we show that ibuzatrelvir maintained its antiviral efficacy against all major SARS-CoV-2 variants circulating between 2020 and 2024 (alpha (α), beta (β), gamma (γ), lambda (λ), delta (δ), mu (μ) and omicron (ο)). Additionally, we characterized the in vitro resistance profile of ibuzatrelvir by selecting viral mutations under drug pressure. This approach identified several resistance-associated amino acid substitutions in Mpro, including T21I, L232R, and S144A, as well as substitution combinations E166V+L232R and S144A+L232R+L253L/F. Among these, the E166V+L232R double substitution conferred the highest level of resistance to ibuzatrelvir. Surveillance studies have shown very low prevalence of the E166V substitution in both GISAID datasets and in breakthrough cases from clinical trials. Cross-resistance testing revealed that this double substitution retained susceptibility to remdesivir and also conferred resistance to nirmatrelvir. Ibuzatrelvir and nirmatrelvir remained active against viruses containing the ensitrelvir-specific resistance Mpro substitution M49L. The sustained efficacy of ibuzatrelvir against circulating variants, combined with the low prevalence of the E166V substitution, supports its continued evaluation in phase 3 studies.

Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral infection associated with high morbidity and mortality. Understanding the metabolic alterations associated with the disease may uncover novel biomarkers for diagnosis and disease severity assessment. In this study, we conducted a targeted metabolomic analysis using LC-MS/MS to quantify serum organic acid levels in 115 CCHF-positive patients, 30 CCHF-negative patients, and 45 healthy controls. This is the first study to comprehensively profile organic acid alterations in CCHFV using targeted metabolomics. Our findings revealed that several organic acids, notably alpha-ketoglutaric acid, malic acid, p-hydroxyphenyllactic acid, and 3-hydroxyisobutyric acid, were significantly elevated in CCHFV patients and positively correlated with markers of inflammation and coagulation. These metabolites demonstrated strong prognostic performance for intensive care unit (ICU) admission. Additionally, survival analysis indicated that elevated levels of specific organic acids were associated with increased mortality risk. Pathway enrichment analysis identified dysregulation of the TCA cycle, pyruvate metabolism, and amino acid pathways in CCHF patients. Our results suggest that specific organic acids may serve as novel biomarkers for disease severity and prognosis, offering potential tools for early risk stratification and improved clinical management of CCHF.

Chronic hepatitis B virus (HBV) infection is a major global health problem. Currently, existing antiviral drugs are difficult to achieve a functional cure for chronic hepatitis B (CHB). Therefore, it is necessary to develop new antiviral targets, especially those that can directly target HBV covalently closed circular DNA (cccDNA) in hepatocytes. Here, we identified a conserved SOX6 binding site in the enhancer I (ENI) region of the HBV genome, and found that SOX6 promotes the replication of multiple genotypes HBV through its HMG domain. Mechanistically, SOX6 binds to the conserved binding site located in the HBV ENI region through its HMG domain, thereby promoting HBV replication by enhancing the transcriptional activity of ENI. Moreover, cisplatin and doxorubicin not only promote HBV replication but also promote SOX6 expression. Knocking down the expression of endogenous SOX6 or mutating the SOX6 binding site in the HBV ENI region significantly weakens the direct promoting effect of cisplatin and doxorubicin on HBV replication. In summary, SOX6 promotes HBV replication by enhancing the transcriptional activity of HBV ENI through its HMG domain, suggesting that it can serve as a potential target for regulating HBV cccDNA transcription. In addition, SOX6 participates in the direct promotion of HBV replication by cisplatin and doxorubicin, providing new insights into the molecular mechanisms of tumor chemotherapy related HBV reactivation (HBVr) and potential targets for the prevention of HBVr during tumor chemotherapy.