Explore the vast range of titles available.

Background: Human Immunodeficiency Virus type 1 (HIV-1) remains a major global health challenge. Despite advances in antiretroviral therapy, new prevention strategies are needed, particularly topical microbicides capable of blocking the earliest steps of viral entry. HIV-1 attachment relies on interactions with heparan sulfate proteoglycans on host cell surfaces; therefore, sulfated heparan-mimetic polymers have been explored as antiviral agents. In this context, sulfated chitosan microparticles are designed to mimic natural glycosaminoglycan receptors, acting as biomimetic decoys that prevent viral attachment and entry. Methods: Low-molecular-weight sulfated chitosan (LMW Chi-S) microparticles were synthesized and characterized (SEM, EDS, DLS, FTIR) following US Patent No. 11,246,839 B2. Their antiviral activity was evaluated by incubating the microparticles with high-viral-load HIV-1-positive plasma (~3.5 × 106 copies/mL) to enable viral binding and removal by pull-down. The performance of the synthesized Chi-S microparticles was compared with established heparinoid controls, including soluble heparin and heparin microparticles. Results: Chi-S microparticles exhibited stronger virus-binding and neutralizing capacity than all heparinoid comparators, achieving up to 70% reduction in viral load relative to untreated HIV-1 plasma. In comparison, soluble heparin and heparin microparticles reduced viral load by approximately 53% and 60%, respectively. Subsequent evaluation across multiple tested concentrations confirmed a consistent antiviral effect, indicating that the synthesized Chi-S microparticles maintain robust virus–particle interactions throughout the concentration range examined. Conclusions: These findings demonstrate that LMW Chi-S microparticles possess potent antiviral properties and outperform classical heparinoid materials, supporting their potential application as topical microbicides targeting early HIV-1 entry mechanisms.

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin—a de novo designed synthetic small molecule that captures the biological properties of HDPs—on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture.

Over the past five decades, the emergence and re-emergence of multiple flaviviruses have triggered significant global outbreaks, posing serious threats to public health. Among them, West Nile virus (WNV) is a major cause of mosquito-borne illness, typically presenting as an acute systemic febrile disease and, in some cases, progressing to the central nervous system involvement. No specific antiviral therapies or effective vaccines are available for WNV infections. In this context, antimicrobial peptides (AMPs) with antiviral properties—known as antiviral peptides (AVPs)—have gained attention as potential therapeutic agents due to their ability to interfere with various stages of the viral life cycle. Two frog-derived melittin-like peptides, AR-23 and RV-23, were synthesized and purified, and their hemolytic activity was assessed on human erythrocytes. Antiviral activity against WNV was evaluated in Vero cells using cytopathic effect reduction assays and real-time PCR quantification of viral RNA. Time-of-addition experiments were conducted to explore the stage of viral inhibition. In silico molecular docking studies were performed to examine interactions between the peptides and the viral E glycoprotein. Both peptides displayed strong antiviral effects during the early phases of infection, likely through direct interaction with viral particles and disruption of virus–host interactions. Compared with melittin, AR-23 and RV-23 showed greater efficacy and lower cytotoxicity, highlighting their potential as promising therapeutic candidates for flavivirus infections.

The binding properties of synthetic and recombinant peptides derived from N-terminal part of ACE2, the main receptor for SARS-CoV-2, were evaluated. Additionally, the ability of these peptides to prevent virus entry in vitro was addressed using both pseudovirus particles decorated with the S protein, as well as through infection of Vero cells with live SARS-CoV-2 virus. Surprisingly, in spite of effective binding to S protein, all linear peptides of various lengths failed to neutralize the viral infection in vitro. However, the P1st peptide that was chemically “stapled” in order to stabilize its alpha-helical structure was able to interfere with virus entry into ACE2-expressing cells. Interestingly, this peptide also neutralized pseudovirus particles decorated with S protein derived from the Omicron BA.1 virus, in spite of variations in key amino acid residues contacting ACE2.

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54–92% of patients and normalization of alanine transaminase (ALT) in 48.8–74% of patients after 23–144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance.

Bovine viral diarrhea virus (BVDV), also known as Pestivirus A, causes severe infection mostly in cattle, but also in pigs, sheep and goats, causing huge economical losses on agricultural farms every year. The infections are actually controlled by isolation of persistently infected animals and vaccination, but no antivirals are currently available to control the spread of BVDV on farms. BVDV binds the host cell using envelope protein E2, which has only recently been targeted in the research of a potent and efficient antiviral. In contrast, RdRp has been successfully inhibited by several classes of compounds in the last few decades. As a part of an enduring antiviral research agenda, we designed a new series of derivatives that emerged from an isosteric substitution of the main scaffold in previously reported anti-BVDV compounds. Here, the new compounds were characterized and tested, where several turned out to be potent and selectively active against BVDV. The mechanism of action was thoroughly studied using a time-of-drug-addition assay and the results were validated using docking simulations.

Herpes simplex virus type 2 (HSV-2) is a highly prevalent human pathogen worldwide that not only causes genital herpes but is also associated with severe health complications, such as neonatal infections and increased susceptibility to HIV. Currently, due to the lack of an effective HSV-2 vaccine and the emergence of more drug-resistant strains, there is an urgent need to develop effective, safe, and affordable anti-HSV-2 medications. The small molecule UCM05 is a novel inhibitor of fatty acid synthase (FASN) and filamentous temperature-sensitive protein Z (Ftsz), with antitumor and antibacterial effects. In this study, we found that UCM05 effectively inhibits both HSV-2 and acyclovir-resistant HSV-2 infections in vitro , significantly improves survival rates in HSV-2-infected mice, and effectively reduces viral titers in tissues. Further, we discovered that UCM05 destroys the membrane integrity of viral particles by directly binding with HSV-2 glycoproteins gB and gD and reduces viral replication by inhibiting viral protein synthesis and fatty acid synthesis. Additionally, UCM05 treatment promoted the generation of type I IFN related genes but does not result in an inflammatory cytokine storm triggered by HSV-2, and it also exhibited activity against co-infection with HIV-1/HSV-2, as well as infection with HSV-1. Overall, our research demonstrates that UCM05 can effectively inhibit HSV-2 infection both in vitro and in vivo . UCM05 represents a potential new antiviral drug against HSV-2.

The development of antivirals for respiratory viruses has advanced markedly in response to the growing threat of pathogens such as Influenzavirus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. This article reviews the advances and challenges in this field, highlighting therapeutic strategies that target critical stages of the viral replication cycle, including inhibitors of viral entry, replication, and assembly. In addition, innovative approaches such as inhibiting host cellular proteins to reduce viral resistance and repurposing existing drugs are explored, using advanced bioinformatics tools that optimize the identification of antiviral candidates. The analysis also covers emerging technologies such as nanomedicine and CRISPR gene editing, which promise to improve the stability and efficacy of treatments. While current antivirals offer valuable options, they face challenges such as viral evolution and the need for accessible treatments for vulnerable populations. This article underscores the importance of continued innovation in biotechnology to overcome these limitations and provide safe and effective treatments. Combining traditional and advanced approaches in developing antivirals is essential in order to address respiratory viral diseases that affect global health.

Background The COVID-19 pandemic renewed global focus on the development of novel antiviral agents. Peptides, owing to their high specificity and tunability, represent a promising therapeutic class. The integrin-binding peptide ATN-161 (Ac-PHSCN-NH₂) has shown potential as a SARS-CoV-2 fusion inhibitor by disrupting α5β1 integrin-mediated entry. Purpose This study aimed to develop and evaluate novel ATN-161 analogues with improved biochemical stability and antiviral activity by introducing proline substitutions into its core sequence. Methods Three analogues, Ac-P P SCN-NH₂ (Analogue-I), Ac-PH P CN-NH₂ (Analogue-II), and Ac-PHS P N-NH₂ (Analogue-III), were synthesized using SPPS, characterized by HPLC, mass spectrometry and NMR spectroscopy. Antiviral activity was assessed in SARS-CoV-2-infected Vero (E6) cells using cytopathic effect monitoring and RT-qPCR. In silico molecular docking and dynamics simulations were performed against α5β1 integrin and ACE2 to evaluate binding affinity and stability. Results Analogue-III demonstrated superior antiviral activity, reducing viral RNA load by ~ 100-fold with an IC 50  = 0.6 µM, outperforming ATN-161 (IC 50  = 3.16 µM), while maintaining a favourable cytotoxicity profile. Docking studies revealed the strongest binding affinities (up to − 17.05 kcal/mol) and lowest RMSD values (as low as 1.113 Å), while dynamics simulations supported stable and favorable interactions. Conclusion Proline-based structural modifications of ATN-161 yielded a promising antiviral candidate with improved activity. Analogue-III (Ac-PHS P N-NH₂) merits further preclinical evaluation as a potential fusion inhibitor targeting integrin-mediated viral entry.