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Povzetek: The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses a challenge to current therapies and emphasises the need for targets that are less susceptible to mutation. The SARS-CoV-2 envelope protein (Epro) is a highly conserved viroporin and is of central importance to the viral life cycle, yet it remains underexplored as a therapeutic target. In this study, we have identified and characterised a novel lead candidate (LC) − (S)-N-(2-((1S,3S,5S,7S)-adamantan-2-yl)ethyl)-2-(butylamino)-3-(1H-indol-3-yl)propanamide − for inhibition of the SARS-CoV-2 Epro ion channel using combined in silico and in vitro approaches. Molecular dynamics (MD) simulations showed that LC forms stable complexes at the N-terminal vestibule, with key interactions at GLU8, THR9, THR11, ASN15, and LEU18, and a calculated binding affinity higher than that of the reference compound rimantadine within the applied MD/molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) framework. Results of in vitro experiments indicated that LC inhibits the model coronavirus murine hepatitis virus at late stages of the viral cycle. Activity under co-treatment conditions further suggests a direct virucidal effect or interference with early entry stages; an EC50 of approximately 12 μM was within the same micromolar range as those observed for the reference Epro inhibitors 5-(N,N-hexamethylene)amiloride and rimantadine. Quantitative PCR experiments showed delayed RNA replication in LC-treated infected cells, while light and transmission electron microscopy displayed the reduced release of virions and prevention of cell lysis. These results emphasise the central role of the Epro ion channel in the coronavirus life cycle and present LC as a promising candidate for the further development of novel coronavirus inhibitors.
Ključne besede: SARS-CoV-2 envelope protein, viroporin, ion channel blockers, molecular docking, molecular dynamics simulations, drug discovery, murine hepatitis virus, in vitro
Objavljeno v DiRROS: 11.06.2026; Ogledov: 240; Prenosov: 254
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Povzetek: Background: Systemic corticosteroids, recommended for adult patients with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, may carry an increased risk of reactivating latent infections such as hepatitis B virus (HBV) infection. Methods: This retrospective observational cohort study of prospectively collected clinical data evaluated HBV screening frequency and examined the prevalence and reactivation of HBV among hospitalised adults treated with systemic corticosteroids for COVID-19 at a tertiary care hospital in Slovenia. Results: Anti-HBc screening was conducted in 1,793/2,134 (84%) hospitalised patients receiving corticosteroids for COVID-19 (median age 70 years [IQR 59‒79 years]; 1,082 [60.3%] were male). Among the 1,793 screened patients, 157 (8.8%) were anti-HBc positive, and 5 (0.3%) of them also HBsAg positive. All five HBsAg-positive patients were aviremic. HBV infection was previously known in three of these patients (two on long-term tenofovir treatment) and identified de novo in two. Entecavir was initiated for one patient. Throughout the hospitalisations and 12-month follow-up periods, no cases of HBV viral rebound were observed in any of the HBsAg positive patients; one of the treated patients succumbed to COVID-19 pneumonia. No HBV reactivation or unexplained hepatopathy occurred in the 152 anti-HBc positive/HBsAg negative patients, none of whom were given antiviral prophylaxis. Conclusions: Corticosteroids for COVID-19 did not appear to be a significant risk factor for HBV reactivation in cases of occult hepatitis B. Universal antiviral prophylaxis in HBsAg negative/anti HBc positive individuals may not be warranted with short courses of corticosteroids for COVID-19 in the absence of other risk factors for HBV reactivation.
Ključne besede: COVID-19, corticosteroids, hepatitis B virus, reactivation
Objavljeno v DiRROS: 15.05.2026; Ogledov: 205; Prenosov: 174
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Povzetek: Viral hepatitis remains a global health concern, with growing recognition of the impact of hepatitis A virus (HAV), hepatitis E virus (HEV), and herpesvirus-associated hepatitis, particularly in vulnerable groups. This narrative review from the ESCMID Study Group for Viral Hepatitis (ESGVH) summarizes recent advances and expert perspectives. For HAV, insights into viral evolution, epidemiology, and risk groups underline the preventable nature of severe disease. HEV is increasingly recognized as both a hepatotropic and a systemic pathogen, with expanding knowledge on natural and vaccine-induced immunity. Herpesvirus-associated hepatitis, while rare, poses significant challenges, especially in patients with immunosuppression or during pregnancy, where early suspicion and empirical antiviral therapy can be lifesaving. Collectively, these evolving insights highlight the importance of strengthened diagnostics, targeted prevention, and tailored management strategies to mitigate the burden of these underappreciated but clinically significant causes of viral hepatitis.
Ključne besede: viral hepatitis, HAV, HEV, hepatitis A, hepatitis E, herpesvirus, liver
Objavljeno v DiRROS: 22.04.2026; Ogledov: 295; Prenosov: 99
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Povzetek: The Visegrad Group – the Czech Republic, Hungary, Poland and Slovakia – face shared challenges in preventing and controlling viral hepatitis. A regional meeting convened by the Viral Hepatitis Prevention Board evaluated health systems, epidemiology, and national policies, revealing accomplishments and needs for prevention, screening, diagnosis, and linkage to care of viral hepatitis. Universal hepatitis B (HBV) vaccination exists, yet vaccine hesitancy and incomplete coverage threaten progress, while surveillance and registries remain fragmented. Access to hepatitis C (HCV) treatment has improved recently, but remains centralized, with limited engagement of marginalized populations. Elimination of HCV by 2030 is unlikely due to insufficient screening, COVID-19-related healthcare disruptions, and weak political commitment, whereas HBV control depends on maintaining high vaccination coverage and robust monitoring. Participants called for harmonized national guidelines, strengthened regional collaboration, and sustainable action plans backed up by political commitment. Urgent, coordinated efforts are needed to achieve the WHO 2030 elimination goals.
Ključne besede: viral hepatitis, hepatitis C, Viral Hepatitis Prevention Board
Objavljeno v DiRROS: 24.03.2026; Ogledov: 373; Prenosov: 196
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Povzetek: Background: With the advent of direct acting antivirals (DAAs) the World Health Organisation (WHO) adopted global strategy to eliminate hepatitis C virus (HCV) infection by 2030. In Europe, people who inject drugs (PWID) account for the majority of new cases, however testing and treatment remain suboptimal. The aim was to monitor progress in HCV policy and cascade-of-care for PWID, led by the civil society organisations (CSO) that provide harm reduction services for PWID across Europe. Methods: In period 2020–2023, CSOs representing focal points of Correlation-European Harm Reduction Network were annually invited to complete online questionnaire on use/impact of HCV test-and-treat guidelines for PWID, availability/functioning of continuum-of-care, and role/limitations of harm reduction services for PWID. A retrospec‑ tive longitudinal analysis of responses to questions answered each year by the same respondents was performed, and a comparison among the studied years was made. Results: Twenty-fve CSOs from cities in 25 European countries were included and responded to 25 questions. Between 2020 and 2023, there was positive trend in number of HCV treatment guidelines, separate guidelines for PWID, and their positive impact on acess to testing/treatment (24/25, 5/25, and 16/25 in 2023, respectively). DAAs were available in all countries, predominantly prescribed by specialist physicians only (slight increase at primary care), with restrictions including active drug use, stage of liver fbrosis or/and reimbursement policies (2/25, 4/25, and 3/25 in 2023, respectively). A decrease in HCV testing sites was noted. Treatment was consistently most common at clini‑ cal settings, however an increase outside the specialist settings was detected, particularly in prisons (12/25 and 15/25 in 2020–2021, respectively). Comparing 2022–2023, number of HCV-testing services increased in many cities with positive dynamic in nearly all the settings; increase in treatment at harm reduction services/community centres was noted (6/25 to 8/25, respectively). Between 2020 and 2023 the frequency of various limitations to CSOs address‑ ing HCV was oscillating, presenting an increase between 2022 and 2023 (9/25 to 14/25, respectively). Conclusion: The overall progress towards WHO HCV elimination goals across Europe remains insufcient, most probably also due to the infuence of Covid-19 pandemic. Further improvements are needed, also by including CSOs for PWID in continuum-of-care services, and in monitoring progress
Ključne besede: hepatitis C, people who inject drugs, continuum-of-care, civil society, harm reduction, monitoring
Objavljeno v DiRROS: 10.03.2026; Ogledov: 417; Prenosov: 258
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