Reviews in Medical Virology最新文献

The Hepatitis C virus genotype 6 (HCV GT6), found in mainland Southeast Asia and Southern China, poses treatment challenges due to its genetic diversity. This systematic review and meta-analysis compared the efficacy and safety of two pan-genotypic direct-acting antiviral regimens, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), for treating chronic HCV GT6. We followed PRISMA guidelines and searched PubMed, Embase, and the Cochrane Library for trials and studies. The primary outcome was the 12-week sustained virologic response (SVR₁₂). We performed single-arm meta-analyses of proportions using methods robust for proportion data with prevalent boundary values and calculated the pooled risk difference (RD) for head-to-head comparisons. Twenty-seven studies published between 2015 and 2025, comprising 1522 patients (451 GLE/PIB and 1071 SOF/VEL), were included. The pooled single-arm SVR₁₂ rate for SOF/VEL was a highly consistent 99.0% (95% Confidence Interval (CI): 98.2%-99.4%). The initial pooled rate for GLE/PIB was 95.6% (95% CI: 93.2%-97.1%) with significant heterogeneity; however, a sensitivity analysis removing outlier studies yielded a rate of 99.2% (95% CI: 97.2%-99.8%) with no heterogeneity. Direct comparison across two studies found no significant difference in efficacy (pooled RD: 0.01, 95% CI: -0.01 to 0.02). Both regimens were exceptionally well-tolerated, with treatment discontinuation rates near zero. GLE/PIB and SOF/VEL are clinically equivalent to treating HCV GT6, achieving near-universal cure rates with excellent safety profiles. Regimen selection should consider practical factors such as GLE/PIB's shorter 8-week duration, comorbidities like cirrhosis, drug interaction profiles, and local cost-effectiveness, rather than minor efficacy differences.

In their review, Li et al. present a compelling framework linking arboviral infections to the dysregulation of osteogenic signalling pathways as a mechanistic basis for musculoskeletal complications. While we applaud this synthesis, our letter provides a critical appraisal to identify pivotal challenges that must be surmounted to translate this concept into viable therapies. We contend that the proposed strategy of targeting pathways like BMP or Wnt oversimplifies their profound context-dependency and pleiotropy, where systemic modulation risks unforeseen consequences like ectopic calcification or exacerbated inflammation. Furthermore, the causal nexus between direct viral manipulation of these pathways and indirect, bystander immunopathology remains ambiguously defined, critically impacting therapeutic choice. The translational pathway is further hampered by the lack of a temporal framework for intervention and the inadequacy of current preclinical models to mimic the human bone-immune-viral milieu. We conclude that while the hypothesis is innovative, its validation demands a more nuanced, systems-level research agenda that rigorously addresses these complexities before therapeutic potential can be realized.

Vaccination is an effective response to the COVID-19 pandemic, but vaccine hesitancy is a major challenge. This study aims to explore the pooled prevalence and factors of COVID-19 vaccine hesitancy. We searched the studies published from January 2020 to December 2023 in PubMed, Web of Science, and Embase. The studies with complete start time of the study and national information were included in the generalised additive model to explore the factors affecting the COVID-19 vaccine hesitancy rate by calculating OR and 95%CI. A total of 629 studies were included. The pooled global hesitancy rates of COVID-19 vaccine were 34.6% (95% CI: 31.2%-38.1%) in vulnerable population and 33.2% (95% CI: 31.7%-34.8%) in general populations. The regression model showed that the hesitancy rate of COVID-19 vaccine was correlated with the duration of the epidemic, the monthly governmental stringency index, the monthly incidence and mortality of COVID-19, SDI, geographical location, and health status. Local governments should pay special attention to vaccination of vulnerable population and encourage vaccination to cope with the next possible wave of pandemic as incidence declines and restrictions are eased. The international community should timely provide vaccines for low economy countries.

In their comprehensive review, Shekhar et al. (Rev Med Virol. 2025; 35:e70067) provide a valuable synthesis of the viral envelope (E) protein's role in subverting innate immunity and its potential as a pharmacological target. While we commend this timely work, our letter offers a critical perspective on the translational challenges and complexities that warrant deeper consideration. We argue that the context-dependent functionality of the E protein-wherein its immunomodulatory effects vary with infection stage, cell type, and viral load-poses a significant hurdle for therapeutic intervention, potentially limiting the efficacy of direct viroporin inhibitors. Furthermore, we highlight emerging mechanisms beyond those extensively covered, such as the E protein's role in inducing ER stress-mediated cellular dysfunction and its newly discovered capacity to degrade STAT2 via selective autophagy, thereby broadly suppressing interferon signaling. The structural intractability of the small, oligomeric E protein to conventional small-molecule drugs is another substantial barrier, shifting the focus towards host-directed therapies. Finally, we critically examine the evolutionary dynamics of this conserved target, emphasizing the need for combination strategies to preempt resistance. This critique aims to refine the roadmap for future research by underscoring the necessity for a nuanced, mechanism-driven, and translationally-aware approach to targeting the E protein.

Simian Virus (SV) 40 is a DNA virus that remains dormant in the body but occasionally induces tumours in animals. Evidence indicates that SV40 could be crucial in developing certain human cancers. There is no commercial vaccine available against SV40. Our study uses a reverse vaccinology strategy to design a vaccine containing the viral Major capsid protein VP1 protein of the Simian virus's B and T-cell epitopes. Eleven MHC-I restricted, ten MHC-II restricted, and five B-cell specific epitopes were prioritised for the design of vaccine model, based on non-allergenicity as a crucial feature and an antigenicity score of > 0.4. An immunogenic and stable vaccine design was generated using the 6-histidine tag, including a 30S ribosomal protein AS04 as an adjuvant with linkers (EAAAK, GPGPG, and AYY). Highly broad-spectrum vaccine was generated with 99.75% of global population coverage. Ramachandran score of 91.7% indicated the structural stability of the designed vaccine. The immunological simulations presented that a persistent antibody response occurred even if the antigen was expelled. IgM + IgG titres were predicted to rise to 6000 after 10 days of injection, and stabilised at 3000 after 30 days, suggesting that the vaccine is effective and provides long-lasting protection against SV40. Molecular docking and MD simulation analyses were performed to study the stability and dynamic confirmation of the designed vaccine model and immune receptor (8JBV), validating strong molecular interactions, hence triggering innate and immune responses against the SV40. Further immunological assays are required to validate the results of this study.

The Envelope (E)-protein is a key structural element of enveloped viruses that plays a significant role in host-pathogen interactions, viral growth, and hijacking of host innate immune system. Due to lack of antiviral agents and significant adverse effects and less affordability of vaccines, the E-protein targeted drug development is gaining critical attention among the researchers. The present review explores the structural and genomic diversities of E-protein among animal viruses with special interest to flaviviruses, coronaviruses, and herpesviruses. E-protein's viroporin activity damages host cell membrane and induces inflammation that advances the disease progression. The review also explains the viroporin-mediated NOD-like receptor family pyrin domain-containing 3 (NLRP3), Toll-like receptors (TLRs), nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs), and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-linked cellular mechanisms in virus-mediated inflammation. The E-protein is considered an alternative promising antiviral target as its functional domain is conserved. This review further enlists the natural, and synthetic inhibitors of E-protein in the development of antiviral agents based on computational, in vitro, and in vivo studies. The E-protein's universal conservation ability to fasten to cellular membranes and limited structural data imparts significant challenge to selective drug inhibition. The present review highlights that the E-protein together with multiple viral factors will boost treatment performance while minimising viral resistance. In addition, broad-range inhibitors targeting E-proteins have the potential to produce single treatment solutions in combating viral infections including several viral strains. In conclusion, E-protein targeted drug would be beneficial in developing potential antiviral agents with high drug specificity, and less viral resistance.

Japanese encephalitis virus (JEV) and dengue virus (DENV) are two major arboviruses known as significant public health issues worldwide. Arboviruses are a heterogeneous group of vector-borne viruses that are clinically associated with various consequences ranging from asymptomatic infections to serious forms of haemorrhagic fever marked by bleeding complications. Despite advancements in understanding the pathogenesis of arboviruses the molecular mechanisms underlying clinical outcomes remain incompletely understood. Autophagy, a cellular process crucial for maintaining homeostasis through the degradation and recycling of cellular components, has emerged as a key player in viral infections. Recent studies have highlighted the dual role of autophagy in modulating the host-pathogen interaction, where it may serve as both a defence mechanism against viral replication and a tool exploited by viruses to enhance survival. In the case of arboviruses, autophagy appears to influence viral replication and modulate the host immune response, contributing to both viral persistence and the extent of clinical outcomes. This review describes the role of autophagy in the pathogenesis of JEV and DENV, focusing on the molecular mechanisms that govern autophagic processes and their interaction with JEV and DENV replication. It shows that how JEV and DENV manipulates host autophagic machinery to its advantage, the impact of autophagic dysregulation on disease severity, and potential therapeutic strategies targeting autophagy to mitigate viral encephalitis. Understanding the intricate balance between autophagy and JEV and DENV may provide novel insights into therapeutic approaches for combating these viruses.

Dengue virus is a neurotropic virus capable of infecting the supporting cells of the central nervous system. One of the most severe neurological consequences of this infection is intracerebral haemorrhage, which is a leading cause of death worldwide. This study aimed to systematically review and analyse the existing literature on this topic, providing insights into the potential neurological consequences for patients with dengue fever. A comprehensive search was conducted across the PubMed, Scopus, Web of Science, and Embase databases to extract relevant published data up to February 2025. This meta-analysis included articles that were designed as cohort studies. A critical appraisal was conducted using the Newcastle-Ottawa Scale (NOS) score. Risk was employed as a measure of pooled effect size based on a random-effects model. Heterogeneity was assessed using the Q test and the I² index. This meta-analysis included 6 studies involving a total of 2861 individuals who directly assessed the risk of intracerebral haemorrhage. The reported risk of intracerebral haemorrhage was 14 cases per 1000 dengue fever patients [0.014 (95% CI: 0.002, 0.026), p = 0.020, I² = 94.64%]. Notably, prospective studies with low methodological quality indicate a higher risk of intracerebral haemorrhage compared to retrospective studies and those of high quality. Given the high risk of intracerebral haemorrhage in patients with dengue fever, it is essential for physicians to evaluate affected individuals for the potential occurrence of cerebral haemorrhage.

Chronic obstructive pulmonary disease (COPD) is a progressive condition affecting the lungs, marked by persistent respiratory symptoms. The prevalence and the risk of COPD in arboviruses types is not fully addressed clinically. We aim to determine the prevalence and the risk of COPD in arboviruses by a systematic review and meta-analysis. A comprehensive literature review was conducted systematically across several databases, including PubMed/Medline, Scopus, Web of Science (WoS), and Embase to find relevant studies up to April 30, 2025. A random-effects model was employed to analyse the relationship between the presence of arboviruses and the clinical implications associated with COPD. This systematic review and meta-analysis was conducted following the standard methodology outlined in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol. We identified 17 studies that met the inclusion criteria for this analysis. The prevalence of COPD in individuals with arbovirus was (10%, 95% CI 6%-13.5%). Moreover, the prevalence of COPD was in dengue virus (5.2%, 95% CI 3.2%-8.2%), chikungunya virus (26.4%, 95% CI 9.7%-54.3%) and West Nile virus (7.6%, 95% CI 4.9%-11.7%). The summary odds ratio (SOR) showed a significant risk of COPD in chikungunya virus (5.1, 95% CI 2.08-12.8) and West Nile virus (1.7, 95% CI 1.25-2.5) but not in patients with dengue virus. Subgroup analysis demonstrated significant association between severity COPD with age and type of study design. Higher prevalence of COPD was found in individuals with chikungunya virus compared with other arboviruses. Findings of the current study will help to public health practitioners and clinicians for better understanding and proper management of COPD in individuals with arbovirus in general population.