Search Results (141)

SARS-CoV-2, the causative agent of COVID-19, has led to over seven million deaths worldwide prior to May 2025. Despite widespread vaccination programs, COVID-19 remains a persistent global health challenge, underscoring the urgent need for new therapeutic approaches. Orientin is a flavonoid with reported antiviral activity, though its potential against SARS-CoV-2 remains poorly explored. This study aimed to investigate whether Orientin interacts with the viral Spike protein and impacts viral replication. Molecular docking simulations using DockThor were employed to predict the binding affinity between Orientin and the receptor-binding domain (RBD) of the Spike protein. Fluorescence spectroscopy assays were performed to assess direct interactions between Orientin and the trimeric form of the Spike protein. Additionally, cytotoxicity and viral replication assays were carried out in Vero cells to evaluate Orientin’s antiviral effects. Docking results indicated that Orientin likely binds to key RBD residues involved in ACE2 receptor recognition. Spectroscopic analyses showed a decrease in intrinsic tryptophan fluorescence, suggesting direct interaction. Orientin demonstrated no cytotoxicity in Vero cells and exhibited moderate inhibition of viral replication. These findings suggest that Orientin interacts with critical regions of the Spike protein and may act as a moderate in vitro inhibitor of SARS-CoV-2, warranting further investigation into its therapeutic potential. Full article

Conventional ultrasound (US) has long been central to hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, due to its low cost, wide availability, non-invasiveness, and adequate sensitivity for detecting small nodules. However, its specificity in distinguishing HCC from other lesions is limited. Contrast-enhanced ultrasound (CEUS) has significantly improved the characterization of nodules first identified on conventional US. Yet, when CEUS is performed using sulfur hexafluoride (SonoVue)—the only contrast agent available in Western countries—assessment remains restricted to a single nodule per examination, and enhanced CT or MRI is still required for full characterization and staging. In clinical settings, such as hepatology, internal medicine, infectious diseases, and surgery, CEUS offers the advantage of immediate availability, enabling rapid characterization of suspicious nodules in cirrhotic livers and facilitating timely therapeutic decisions. Although the introduction of direct-acting antivirals (DAAs) has substantially reduced HCV-related HCC, HCC incidence is increasingly driven by metabolic dysfunction-associated steatohepatitis (MASH). Evidence on surveillance strategies for MASH patients remains limited, and current EASL guidelines recommend monitoring only patients with >F2 fibrosis. Additionally, the effectiveness of US in obese or diabetic/obese populations is under ongoing investigation; abbreviated non-contrast MRI has been proposed as an alternative surveillance tool, but its adoption would entail significant economic implications for healthcare systems. HCC arising from MASH—sometimes even without cirrhosis—exhibits different sonographic and pathological features. Instead of small, hypoechoic nodules, typically seen in HCV-related cirrhosis, clinicians increasingly encounter larger or multiple lesions, often accompanied by macrovascular invasion, limiting access to curative treatments. Furthermore, typical CEUS LI-RADS patterns are less frequently observed. This review summarizes the evolving US findings in the era of MASH-related HCC and underscores the continued importance of US as the primary imaging tool in routine clinical practice. Full article

People who use crack cocaine (PWUCC) constitute a key population due to vulnerability and marginalization, especially in a socio-ecologically diverse, relatively isolated region with limited public health infrastructure. This study aimed to perform a genetic characterization of circulating HCV among PWUCC in the municipality of Bragança, situated on the Brazilian Amazon coast, identifying viral genotypes, subtypes, resistance-associated substitutions (RAS)—naturally occurring mutations in the viral genome that can reduce the efficacy of direct-acting antiviral (DAA) agents—and predictions of phenotypic resistance. Methods: Between 2016 and 2018, biological samples and epidemiological data were obtained from 165 PWUCC. Viral detection was performed using RT-PCR, while genotyping, subtyping, and RAS profiling were conducted through nucleotide sequencing and fragment analysis. Results: In 165 PWUCC, 22 (13.3%) tested positive for HCV RNA. Most of them had not had access to public health services (91.5%), and more than half (57.0%) reported living in unstable housing conditions. HCV subtypes 1a (27.3%), 1b (40.9%), and 3a (31.8%) were detected. Evidence of resistance associated with DAAs, such as daclatasvir and dasabuvir, was detected in five PWUCC with HCV (22.7%). Conclusions: The high prevalence of HCV infection, predominantly subtype 1b, and significant levels of resistance are very concerning. This demonstrates the urgent need for targeted public health interventions to expand access to testing, treatment, and effective antiviral therapy in this vulnerable population of the Brazilian Amazon. Full article

Background/Objectives: Coxsackievirus B3 (CVB3), a neurotropic enterovirus, is a major causative agent of viral encephalitis and myocarditis, yet no protective vaccine or effective antiviral therapy is currently available. Autophagy plays a dual role in viral infections, acting as both an antiviral defense and a process that can be exploited by certain viruses. Although CVB3 has been proposed to utilize autophagosomes as replication platforms, the underlying mechanisms remain controversial. Methods: In this study, we investigated the relationship between CVB3 replication and autophagosome formation under starvation-induced conditions and in ATG5 knockout cells. Results: While nutrient deprivation robustly induced autophagy, CVB3 infection did not trigger autophagosome formation. Moreover, viral replication proceeded efficiently in ATG5-deficient cells lacking autophagosomes. Pharmacological modulation of autophagy using rapamycin, a potent autophagy inducer, did not alter intracellular viral titers or protein expression, although extracellular viral release was modestly reduced. These results indicate that CVB3 replication occurs independently of autophagosome formation, suggesting that pharmacological targeting of autophagy provides limited therapeutic benefit. Conclusions: This study refines our understanding of autophagy as an antiviral target and highlights the need to identify alternative host-directed pathways for antiviral drug development. Full article

Background/Objectives: The prevalence of Hepatitis C Virus (HCV) among men who have sex with men (MSM) is not negligible; however, data from Italy—especially regarding MSM who are not infected with Human Immunodeficiency Virus (HIV)—are limited. We report data from an HCV screening programme targeted at MSM in Rome, starting in 2019 in two hospital settings and in four urban community-based (CB) settings run by non-governmental organizations (NGOs). Methods: Adult MSM (>18 years old) who presented for HIV or sexually transmitted infection testing, or who attended CB activities, were invited to undergo a free-of-charge rapid HCV antibody test (OraQuick HCV^®), after providing informed consent. For all participants, demographic, clinical and behavioural data were collected using an anonymous questionnaire for all participants. Free confirmatory standard serology tests were offered for those found reactive at a rapid HCV test. Individuals with confirmed chronic HCV infection were referred through a dedicated “fast track” pathway for further clinical and laboratory assessment and direct-acting antiviral agents (DAAs) treatment according to the national treatment guidelines. Results: Between July 2019 and July 2023, 2714 MSM agreed to be screened for HCV infection. The median age was 36 years (interquartile range, IQR = 29–46), 91.0% were Italians, 58.0% enrolled in the two clinical centres and 10.7% reported living with HIV (people living with HIV, PLWH). Overall, 9 (0.33%) MSM tested reactive for HCV-specific antibodies using a rapid test. Eight MSM were retested and seven were confirmed to have chronic HCV infection (HCV viremia range: 8 × 10³–23 × 10⁶ IU/mL). The prevalence of confirmed cases was 0.26% (7/2714; 95%CI: 0.10–0.53) and was higher in PLWH compared to those not reporting HIV infection (1.04% vs. 0.17, p = 0.03). Four of seven confirmed HCV cases attended the STI clinic. All confirmed HCV cases reported high-risk behaviours for HCV infection and/or history of sexual transmitted infection (STI). Bening a PLWH (OR = 6.30) and current/former IDU (O = 17.02) resulted in being significantly associated with HCV infection. Other risk factors such as fisting, groupsex, chemsex and condomless anal intercourse were more common in the HCV case (OR > 2), but lacked statistical significance, likely due to small sample size. All seven individuals were linked to care, clinically assessed and started on DAAs treatment, achieving sustained viral response (SVR) in all cases. Conclusions: These data suggest the feasibility and potential effectiveness of a preventive programme targeting MSM living in Rome, combining HCV screening, case finding and prompt linkage to care. HCV prevalence in the screened population was lower than anticipated, although it is significantly higher in PLWH and in those with high-risk behaviours. Considering this condition of low prevalence of HCV infection among MSM in Italy, a targeted screening in PLWH and in individuals with high-risk behaviours may be more effective to achieve HCV eradication than universal screening in MSM. Full article

Background: In recent decades, research on Hepatitis C Virus (HCV) drug-resistant variants has expanded; however, critical gaps remain in our understanding of global contributions, emerging trends, and future research directions. Here, we present a bibliometric analysis to understand the research themes and trends in research related to HCV drug-resistant variants published between 1999 and 2025. Methods: Publications related to HCV drug-resistant variants published between 1999 and 2025 were searched on the Web of Science and Scopus databases. Publication metadata and content-based data were extracted and analyzed using Bibliometrix and VOSviewer for keyword co-occurrence plot and cluster analysis. Results: The analysis of 653 articles revealed a clear paradigm shift, driven by the introduction of direct-acting antivirals (DAAs), which led to a significant surge in annual publications, peaking between 2014 and 2018. This shift in focus led to an emphasis on DAA efficacy, resistance mechanisms, and advanced genotyping. The United States was the most productive country, with the highest number of publications (n = 134) and citations (n = 6458). The University of São Paulo was the most productive institution (n = 40), while Antimicrobial Agents and Chemotherapy published the highest number of articles in this field (n = 40). Susser S. was the most productive researcher. Collaboration networks were found to be predominantly centered in high-income countries. Analysis of studies on minority variants showed that most studies originated from Europe and the United States, identifying low-frequency resistance-associated substitutions (RASs) such as A156V, D168V, Y93H, and S282T, with prevalence ranging from <1% to 35%, which were frequently associated with viral breakthrough and reduced treatment response. Conclusions: The field successfully transitioned to the DAA era, but research output and collaboration networks were primarily driven by high-income countries, leaving a critical gap in data from Low- and Middle-Income Countries (LMICs). Closing this gap by integrating LMIC data is the next essential step to ensure global elimination strategies are effective for all countries from different income strata. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge, partly due to the prolonged duration and toxicity of standard antibiotic regimens. Adjunctive therapies that enhance antimicrobial efficacy and modulate host immunity are urgently needed. Curcumin, a natural bioactive compound derived from Curcuma longa, possesses broad therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and antiviral effects. This study evaluated the effects of curcumin in combination with first- and second-line antibiotics against Mtb in both in vitro and in vivo models. Our results demonstrated that curcumin exerts direct antibacterial activity against both the drug-sensitive H37Rv strain and a multidrug-resistant (MDR) clinical isolate. Furthermore, curcumin synergized with conventional antibiotics, enhancing bacterial clearance in infected macrophages while promoting the production of IL-12, a key cytokine in protective immune responses. In a murine model of progressive pulmonary TB, combination therapy with curcumin and first-line antibiotics significantly reduced the lung bacterial burden and improved behavioral outcomes compared to antibiotic treatment alone. These findings suggest that curcumin acts through both direct antimicrobial mechanisms and immune modulation, supporting its potential as an adjunctive therapy agent for TB. Future studies should focus on optimizing curcumin formulation, dosing, and bioavailability to facilitate the clinical translation of this compound. Full article

Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management, offering high cure rates, favorable safety, and simplified regimens. Management in immunosuppressed patients remains challenging due to drug–drug interactions (DDIs). The objective of this review is to summarize clinical outcomes, safety, and pharmacologic considerations of DAA therapy in immunosuppressed patients, including solid organ transplant recipients and those on biological agents. We reviewed clinical studies, pharmacologic databases, and guidelines to characterize DAA classes, mechanisms, and relevant DDIs in immunosuppressed HCV patients. In transplant recipients, DAAs achieved sustained virological response (SVR) > 90% with minimal graft rejection. Safety profiles were favorable, and immunosuppressant dose adjustments were rarely needed. DDIs, particularly with calcineurin inhibitors (tacrolimus, cyclosporine), require careful monitoring due to variable trough-level effects. Evidence also supports the efficacy and safety of DAAs in patients on biological agents, without compromising SVR. Pharmacokinetic data indicate DAAs maintain antiviral activity across HCV genotypes in the presence of immunosuppressants, though mTOR inhibitors may alter efficacy in certain HCV genotypes. DAAs are highly effective and safe in immunosuppressed patients, achieving high SVR rates and potential graft survival benefits. Prospective studies are needed to assess DAA therapy in patients receiving biological agents and to optimize co-administration strategies with immunosuppressive agents. Full article

Background/Objectives: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effects against the SARS-CoV-2 virus. Methods: Compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues, were evaluated in vitro against SARS-CoV-2 to a antiviral activity and inhibitory effect against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect affecting the interaction between the receptor-binding domain (RBD) protein and/or ACE2 was evaluated using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of the compounds after 3 days of treatment. Results: Compounds PQM-243 and PQM-249 exhibited IC₅₀ values of 0.0648 ± 0.041 µM and 0.2860 ± 0.057 µM against SARS-CoV-2 with a selective index of >1543.21 and 349.65, respectively, and IC₅₀ values of 12.1 nM and 13.3 nM, respectively, against ACE2. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational studies suggest that these new compounds are potent direct anti-SARS-CoV-2 agents, capable of reducing both virus viability and its invasive ability in the host cells by reducing the interaction between RBD and ACE2. It was also demonstrated that even when administered by the oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Our data suggests that both compounds can act as potent direct anti-SARS-CoV-2 agents, reducing both viral viability and host cell entry. In addition, they exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally. Conclusions: Overall, these findings support further investigation of PQM-243 and PQM-249 as promising antiviral and anti-inflammatory multi-target prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases. Full article

Hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) remain leading drivers of chronic viral hepatitis, cirrhosis, hepatocellular carcinoma, and liver-related mortality. This ESCMID Study Group for Viral Hepatitis (ESGVH) narrative review summarizes recent advances and expert perspectives in the field. For HBV, emerging biomarkers such as quantitative HBs antigen, HBV RNA, and hepatitis B core-related antigen offer opportunities to refine monitoring and to individualize treatment. HDV epidemiology is evolving, and is being increasingly studied; in parallel, the approval of bulevirtide represents a major breakthrough in therapy, with further agents in the HDV pipeline. For HCV, direct-acting antivirals provide curative therapy and have made elimination a realistic goal, while identifying remaining gaps in diagnosis, linkage-to-care, and equitable access offers clear opportunities to accelerate progress. Together, these advances bring the goal of a hepatitis-free future closer than ever. Full article

Enteroviruses, a diverse genus within the Picornaviridae family, are responsible for a wide range of human infections, including hand, foot, and mouth disease, respiratory disease, aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis. Despite their substantial global health burden and the frequent emergence of outbreaks, no specific antiviral therapies are currently approved for clinical use against non-polio enteroviruses. This review provides a comprehensive overview of the current landscape of antiviral strategies targeting enteroviruses, including direct-acting antivirals such as capsid binders, protease inhibitors, and viral RNA polymerase inhibitors. We also examine the potential of host-targeting agents that interfere with virus–host interactions essential for replication. Emerging strategies such as immunotherapeutic approaches, RNA interference, CRISPR-based antivirals, and peptide-based antivirals are also explored. Furthermore, we address key challenges, including viral diversity, drug resistance, and limitations in preclinical models. By highlighting recent advances and ongoing efforts in antiviral development, this review aims to guide future research and accelerate the discovery of effective therapies against enterovirus infections. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease’s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats. Full article

Introduction: The implementation of nationwide viral hepatitis C elimination programs is challenging in Central and Eastern European countries (CEEC). It is reasonable to start by targeting specific populations, such as people living with HIV (PLWH), who are at higher risk of acquiring HCV or developing HCV-related complications. Methods: Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 26 countries in the region. Between April 26th and June 23rd 2023, the group performed an on-line survey consisting of 32 questions. The questionnaire assessed the status of HCV micro-elimination in 2022. Results: Twelve HIV centers from 11 countries responded: Albania, Bosnia and Herzegovina, Croatia, Czech Republic, Estonia, Greece, Hungary, Macedonia, Moldova, Serbia and Ukraine. All centers screen for HCV antibody all PLWH at entry into care. The seroprevalence of anti-HCV was <5% in 5 centers (Albania, Croatia, Serbia, North Macedonia and Hungary), 30.2% in Estonia and 29% in Ukraine, Greece and Moldova had high seroprevalence as well, 15.3% and 15.6% respectively. The prevalence of HCV viremia in antibody-positive PLWH was very high in Greece (85%), while in most other treatment centers it ranged from 4.2% to 38.2%. There is also a screening policy of annual HCV-testing of HCV-antibody negative persons in all centers by either testing all PLWH or those considered at risk. Direct-acting antiviral agents (DAA) were not available in one country (Albania). Among PLWH who entered care in 2022, nine out of 12 ECEE centers reported cases of HCV/HIV coinfection, with five centers indicating that at least 50% of these individuals were HCV-viremic. Conclusions: HCV screening in PLWH followed by access to DAA treatments were available in all but one center. Microelimination of HCV in PLWH in the majority of surveyed HIV treatment centers in CEEC has not been achieved and efforts to reach this goal need to be strengthened. Full article

Background. To meet the WHO’s viral hepatitis elimination goal by 2030, the Minister of Health (Italy) introduced free HCV screening among people born between 1969 and 1989 and those at greater risk (people in the care of the addiction services and detained). Aims. To estimate the following: (i) the prevalence of HCV in hospitalized patients born before 1969 not included in the free HCV screening, (ii) the prevalence of transaminase values outside the range, and (iii) the HBV prevalence in a subgroup of patients. Methods. Anti-HCV antibodies and transaminase values were prospectively evaluated in patients born before 1969 and admitted to the Santa Maria alle Scotte Hospital in Siena. The first screening (October 2021–July 2022) was conducted in the Internal Medicine Division (cohort 0), and the second one (May 2024–October 2024) in Internal Medicine, Gastroenterology, and Geriatric Units (cohorts 1–3), including clinical features and HBV markers in a subgroup of patients. Results. Overall, 774 subjects underwent HCV screening. In the first screening period, 1.4% (8/567) of patients were anti-HCV+, of whom 0.7% were HCV RNA+ (4/567). In the second, 3.9% of patients (8/207) were anti-HCV+ and 0.9% were viremic (2/207). Overall, HCV prevalence was 0.8%. Of 96 patients in the gastroenterology cohort, 8 patients were at risk for occult HBV infection (8.3%). Conclusions. Our study demonstrates a chronic HCV infection prevalence of 0.8% in hospitalised patients born before 1969 and a prevalence of 8.3% of people at risk for occult HBV infection in a subgroup of patients residing in South-Eastern Tuscany, confirming that an opportunistic screening can identify the unrecognized people affected by viral hepatitis. Full article