Search Results (80)

The recent discovery of Orthonairovirus songlingense (SGLV) and Norwavirus beijiense (BJNV) in China has raised significant concern due to their potential to cause severe human disease. However, little is known about the structural features and function of their nucleoproteins, which play a key role in the viral life cycle. By combining small-angle X-ray scattering (SAXS) data and AlphaFold 3 simulations, we reconstructed the BJNV and SGLV nucleoprotein structures for the first time. The SGLV and BJNV nucleoproteins have structures that are broadly similar to those of Orthonairovirus haemorrhagiae (CCHFV) nucleoproteins despite low sequence similarity. Based on structural analysis, several residues located in the positively charged region of BJNV and SGLV nucleoproteins have been indicated to be important for viral RNA binding. A positively charged RNA-binding crevice runs along the interior of the SGLV and BJNV ribonucleoprotein complex (RNP), shielding the viral RNA. Despite the high structural similarity between SGLV and BJNV nucleoprotein monomers, their RNPs adopt distinct conformations. These findings provide important insights into the molecular mechanisms of viral genome packaging and replication in these emerging pathogens. Also, our work demonstrates that experimental SAXS data can validate and improve predicted AlphaFold 3 structures to reflect their solution structure and also provides the first low-resolution structures of the BJNV and SGLV nucleoproteins for the future development of POC tests, vaccines, and antiviral drugs. Full article

Background and aim: The COVID-19 pandemic, caused by SARS-CoV-2, remains a global health crisis despite vaccination efforts, necessitating novel therapeutic strategies. Natural compounds from Syzygium aromaticum (clove), such as eugenol and β-caryophyllene, exhibit antiviral and anti-inflammatory properties, while host genetic factors, including miR-21 rs1292037 polymorphism, may influence disease susceptibility and severity. This study investigates the dual approach of targeting SARS-CoV-2 via Syzygium aromaticum phytoconstituents while assessing the role of miR-21 rs1292037 in COVID-19 pathogenesis. Methods: Firstly, molecular docking and molecular dynamics simulations were employed to assess the binding affinities of eugenol and caryophyllene against seven key SARS-CoV-2 proteins—including Spike-RBD, 3CLpro, and RdRp—using SwissDock (AutoDock Vina) and the Desmond software package, respectively. Secondly, GC-MS was used to characterize the composition of clove extract. Thirdly, pharmacokinetic profiles were predicted using in silico models. Finally, miR-21 rs1292037 genotyping was performed in 100 COVID-19 patients and 100 controls, with cytokine and coagulation markers analyzed. Results: Docking revealed strong binding of eugenol to viral Envelope Protein (−5.267 kcal/mol) and caryophyllene to RdRp (−6.200 kcal/mol). ADMET profiling indicated favorable absorption and low toxicity. Molecular dynamics simulations confirmed stable binding of methyl eugenol and caryophyllene to SARS-CoV-2 proteins, with caryophyllene–7Z4S showing the highest structural stability, highlighting its strong antiviral potential. Genotyping identified the TC genotype as prevalent in patients (52%), correlating with elevated IL-6 and D-dimer levels (p ≤ 0.01), suggesting a hyperinflammatory phenotype. Males exhibited higher ferritin and D-dimer (p < 0.0001), underscoring sex-based disparities. Conclusion: The bioactive constituents of Syzygium aromaticum exhibit strong potential as multi-target antivirals, with molecular simulations highlighting caryophyllene’s particularly stable interaction with the 7Z4S protein. Methyl eugenol also maintained consistent binding across several SARS-CoV-2 targets. Additionally, the miR-21 rs1292037 polymorphism may influence COVID-19 severity through its role in inflammatory regulation. Together, these results support the combined application of phytochemicals and genetic insights in antiviral research, pending further clinical verification. Full article

With the emergence of the SARS-CoV-2 pandemic the process of coronavirus replication has been under increasing scrutiny. During the replication of their genomic RNA, coronaviruses produce a range of other RNAs in addition to the negative-sense replicative intermediates of the genome, which includes a set of subgenomic RNAs. These subgenomic RNAs are nested within the sequence of the complete genome and can be both replicated further and act as templates for protein production. Alongside these functional products of discontinuous replication, coronaviruses produce defective viral genomes that can potentially impact both the virus and infected host cells. These interactions can arise from the ability of these defective viral genomes to impact the production of new infectious virions, through either competition with the wild-type genome for replication or by stimulating an antiviral response. Examining the behaviour of defective viral genomes can also help to elucidate the functional elements of the genome involved in the processes of replication and packaging. This review covers the process of intracellular replication by coronaviruses describing the mechanisms by which the different RNA species are produced. Of particular focus are factors involved in discontinuous replication that produces defective viral genomes, and the behaviour of coronavirus defective viral genomes. Full article

The SARS-CoV-2 pandemic had widespread and severe impacts on both the global economy and human health. Facing the continuously mutating virus, this crisis has heightened concerns among consumers and businesses regarding viral transmission through seafood, particularly in the face of emerging, unknown viruses, underscoring our preparedness gaps. This review provides a succinct overview of the survival mechanisms of prevalent viruses in seafood, examines potential transmission pathways to humans during seafood processing, and discusses strategies for mitigating their spread throughout the seafood supply chain. Furthermore, the discussion highlights emerging trends in innovative antiviral technologies aimed at enhancing food safety. Person-to-person transmission remains the most likely source of infection within the supply chain. Therefore, it is still imperative to adhere to the implementation of standard processes, namely good manufacturing practices (GMP) and good hygiene practices (GHP), in the seafood business. In light of the significant losses caused by this crisis and the persistent presence of various viruses within the seafood supply chain, efforts are needed to implement predictive and preventive measures against potential emerging viruses. Future research should focus on monitoring and limiting viral transmission by integrating Industry 4.0 applications, smart technologies, and antiviral packaging, maximizing the potential of these emerging solutions. Full article

Kaposi’s Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are few effective treatments available to treat infection and KSHV oncogenesis. Disrupting the KSHV infectious cycle would diminish the viral spread. The KSHV lytic phase and production of new virions require efficient copying and packaging of the KSHV genome. KSHV encodes its own lytic DNA replication machinery, including the processivity factor (PF-8), which presents itself as an attractive target for antiviral development. We characterized PF-8 at the single molecule level using transmission electron microscopy to identify key molecular interactions that mediate viral DNA replication initiation. Our results indicate that PF-8 forms oligomeric ring structures (tetramer, hexamer, and/or dodecamer) similar to the related Epstein–Barr virus processivity factor (BMRF1). Our DNA positional mapping revealed high-frequency binding locations of PF-8 within the lytic origin of replication (OriLyt). A multi-variable analysis of PF-8 DNA-binding activity with three mutant OriLyts provides new insights into the mechanisms that PF-8 associates with viral DNA and complexes to form multi-ring-like structures. Collectively, these data enhance the mechanistic understanding of the molecular interactions (protein–protein and protein-DNA) of an essential KSHV DNA replication protein. Full article

RNA-binding proteins (RBPs) are cellular factors involved in every step of RNA metabolism. During HIV-1 infection, these proteins are key players in the fine-tuning of viral and host cellular and molecular pathways, including (but not limited to) viral entry, transcription, splicing, RNA modification, translation, decay, assembly, and packaging, as well as the modulation of the antiviral response. Targeted studies have been of paramount importance in identifying and understanding the role of RNA-binding proteins that bind to HIV-1 RNAs. However, novel approaches aimed at identifying all the proteins bound to specific RNAs (RBPome), such as RNA interactome capture, have also contributed to expanding our understanding of the HIV-1 replication cycle, allowing the identification of RBPs with functions not only in viral RNA metabolism but also in cellular metabolism. Strikingly, several of the RBPs found through interactome capture are not canonical RBPs, meaning that they do not have conventional RNA-binding domains and are therefore not readily predicted as being RBPs. Further studies on the different cellular targets of HIV-1, such as subtypes of T cells or myeloid cells, or on the context (active replication versus reactivation from latency) are needed to fully elucidate the host RBPome bound to the viral RNA, which will allow researchers and clinicians to discover new therapeutic targets during active replication and provirus reactivation from latency. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the large coronavirus family with high infectivity and pathogenicity and is the primary pathogen causing the global pandemic of coronavirus disease 2019 (COVID-19). Phosphorylation is a major type of protein post-translational modification that plays an essential role in the process of SARS-CoV-2–host interactions. The precise identification of phosphorylation sites in host cells infected with SARS-CoV-2 will be of great importance to investigate potential antiviral responses and mechanisms and exploit novel targets for therapeutic development. Numerous computational tools have been developed on the basis of phosphoproteomic data generated by mass spectrometry-based experimental techniques, with which phosphorylation sites can be accurately ascertained across the whole SARS-CoV-2-infected proteomes. In this work, we have comprehensively reviewed several major aspects of the construction strategies and availability of these predictors, including benchmark dataset preparation, feature extraction and refinement methods, machine learning algorithms and deep learning architectures, model evaluation approaches and metrics, and publicly available web servers and packages. We have highlighted and compared the prediction performance of each tool on the independent serine/threonine (S/T) and tyrosine (Y) phosphorylation datasets and discussed the overall limitations of current existing predictors. In summary, this review would provide pertinent insights into the exploitation of new powerful phosphorylation site identification tools, facilitate the localization of more suitable target molecules for experimental verification, and contribute to the development of antiviral therapies. Full article

Doravarine (DOR) is an antiviral drug with a marketed authorization for the management of occupational blood and body fluid exposure. The currently existing packaging, consisting of multiple unit bottles comprising 30 tablets, is not fully appropriate for daily nominative dispensing at the hospital. This study aims at assessing the impact of the change in packaging on the key attributes of the drug: assay, impurity profile, and dissolution. As the first step, which is not fully depicted in the literature, the main potential impurities that could appear during storage (i.e., degradation products (DPs) of DOR) were characterized using a forced degradation protocol followed by an LC-MS/MS analysis. These results paved the way for in silico toxicological assessment and targeted degradation product profiling. Based on this study, the assessment of the implication of repackaging on the formation of DOR’s degradation products should be a primary focus. Full article

The aim of this study was to cover biopolymeric packaging films based on PLA/PHBV blend with a functional composite coating (to retain their ecological character) and to investigate their antimicrobial properties before and after UV irradiation. As an active coating, the carrier hydroxypropyl methyl cellulose (HPMC), as well as its modified form with Achillea millefolium L., Hippophae rhamnoides L., and Hypericum L. extract (E) and a combined system based on the extracts and nano-ZnO (EZ), was used to obtain active formulations. Additionally, film surface morphology (SEM, FTIR-ATR) and color (CIELab scale) analysis of the pre- and post-UV-treatment samples were performed. The results confirmed that the E and EZ-modified films exhibited antibacterial properties, but they were not effective against phage phi6. Q-SUN irradiation led to a decrease in the activity of E coating against Staphylococcus aureus, Pseudomonas syringae, and Candida albicans. In this case, the effectiveness of EZ against C. albicans at 24 h and 72 h UV irradiation decreased. However, the irradiation boosted the antiviral effectiveness of the EZ layer. SEM micrographs of the film surface showed that UV treatment did not significantly influence the native film morphology, but it had an impact on the coated film. FTIR analysis results showed that the coatings based on HPMC altered the IR absorption of the nonpolar groups of the biopolyester material. The applied coatings only marginally affected film color changes and increased their yellowness after UV irradiation, whereas a composite layer of nano-ZnO limited these changes. Full article

Since the outbreak of COVID-19, researchers have been working tirelessly to discover effective ways to combat coronavirus infection. The use of computational drug repurposing methods and molecular docking has been instrumental in identifying compounds that have the potential to disrupt the binding between the spike glycoprotein of SARS-CoV-2 and human ACE2 (hACE2). Moreover, the pseudovirus approach has emerged as a robust technique for investigating the mechanism of virus attachment to cellular receptors and for screening targeted small molecule drugs. Pseudoviruses are viral particles containing envelope proteins, which mediate the virus’s entry with the same efficiency as that of live viruses but lacking pathogenic genes. Therefore, they represent a safe alternative to screen potential drugs inhibiting viral entry, especially for highly pathogenic enveloped viruses. In this review, we have compiled a list of antiviral plant extracts and natural products that have been extensively studied against enveloped emerging and re-emerging viruses by pseudovirus technology. The review is organized into three parts: (1) construction of pseudoviruses based on different packaging systems and applications; (2) knowledge of emerging and re-emerging viruses; (3) natural products active against pseudovirus-mediated entry. One of the most crucial stages in the life cycle of a virus is its penetration into host cells. Therefore, the discovery of viral entry inhibitors represents a promising therapeutic option in fighting against emerging viruses. Full article

Natural and synthetic polymers are a versatile platform for developing biomaterials in the biomedical and environmental fields. Natural polymers are organic compounds that are found in nature. The most common natural polymers include polysaccharides, such as alginate, hyaluronic acid, and starch, proteins, e.g., collagen, silk, and fibrin, and bacterial polyesters. Natural polymers have already been applied in numerous sectors, such as carriers for drug delivery, tissue engineering, stem cell morphogenesis, wound healing, regenerative medicine, food packaging, etc. Various synthetic polymers, including poly(lactic acid), poly(acrylic acid), poly(vinyl alcohol), polyethylene glycol, etc., are biocompatible and biodegradable; therefore, they are studied and applied in controlled drug release systems, nano-carriers, tissue engineering, dispersion of bacterial biofilms, gene delivery systems, bio-ink in 3D-printing, textiles in medicine, agriculture, heavy metals removal, and food packaging. In the following review, recent advancements in polymer chemistry, which enable the imparting of specific biomedical functions of polymers, will be discussed in detail, including antiviral, anticancer, and antimicrobial activities. This work contains the authors’ experimental contributions to biomedical and environmental polymer applications. This review is a vast overview of natural and synthetic polymers used in biomedical and environmental fields, polymer synthesis, and isolation methods, critically assessessing their advantages, limitations, and prospects. Full article

The goal of this study was to analyze the antifungal and antiviral activity of coatings based on Formitopsis betulina, Verbascum L. and Uncaria tomentosa extracts with ZnO nanoparticles as active compounds. The other purpose was to investigate the impact of polypropylene bags coated with the obtained antiviral/antifungal coatings on the microbial quality/purity of strawberries. The results of this study showed that the analyzed coatings inhibited Candida albicans growth completely. They did not inhibit the growth of Fusarium oxysporum, but they decreased its number. Additionally, all layers demonstrated a high activity against the Φ 6 bacteriophage particles. Analyzing the microbial purity of the strawberries after storage, it was noticed that the modified bags with Verbascum L. (ZnVL) and F. betulina (ZnFb) extracts and the addition of the nano ZnO had a significant effect on the decrease of the total count and on the number of yeast and mold. After 144 h of storage of the strawberries, the ZnVL coating was found to be more effective than the ZnFb layer. However, after 216 h of storage, ZnVL was more active against yeast and mold, but the packaging covered with the ZnFb coating was more effective against bacteria. Full article

Cytomegalovirus (CMV) infections may increase morbidity and mortality in immunocompromised patients. Until recently, standard antiviral drugs against CMV were limited to viral DNA polymerase inhibitors (val)ganciclovir, foscarnet and cidofovir with a risk for cross-resistance. These drugs may also cause serious side effects. This narrative review provides an update on new antiviral agents that were approved for the prevention and treatment of CMV infections in transplant recipients. Letermovir was approved in 2017 for CMV prophylaxis in CMV-seropositive adults who received an allogeneic hematopoietic stem cell transplant. Maribavir followed four years later, with an indication in the treatment of adult and pediatric transplant patients with refractory/resistant CMV disease. The target of letermovir is the CMV terminase complex (constituted of pUL56, pUL89 and pUL51 subunits). Letermovir prevents the cleavage of viral DNA and its packaging into capsids. Maribavir is a pUL97 kinase inhibitor, which interferes with the assembly of capsids and the egress of virions from the nucleus. Both drugs have activity against most CMV strains resistant to standard drugs and exhibit favorable safety profiles. However, high-level resistance mutations may arise more rapidly in the UL56 gene under letermovir than low-grade resistance mutations. Some mutations emerging in the UL97 gene under maribavir can be cross-resistant with ganciclovir. Thus, letermovir and maribavir now extend the drug arsenal available for the management of CMV infections and their respective niches are currently defined. Full article

Selenium nanoparticles (SeNPs) are extremely popular objects in nanotechnology. “Green” synthesis has special advantages due to the growing necessity for environmentally friendly, non-toxic, and low-cost methods. This review considers the biosynthesis mechanism of bacteria, fungi, algae, and plants, including the role of various biological substances in the processes of reducing selenium compounds to SeNPs and their further packaging. Modern information and approaches to the possible biomedical use of selenium nanoparticles are presented: antimicrobial, antiviral, anticancer, antioxidant, anti-inflammatory, and other properties, as well as the mechanisms of these processes, that have important potential therapeutic value. Full article

The incorporation of the metal phase into cellulose hydrogels, resulting in the formation of metallogels, greatly expands their application potential by introducing new functionalities and improving their performance in various fields. The unique antiviral, antibacterial, antifungal, and anticancer properties of metal and metal oxide nanoparticles (Ag, Au, Cu, Cu_xO_y, ZnO, Al₂O₃, TiO₂, etc.), coupled with the biocompatibility of cellulose, allow the development of composite hydrogels with multifunctional therapeutic potential. These materials can serve as efficient carriers for controlled drug delivery, targeting specific cells or pathogens, as well as for the design of artificial tissues or wound and burn dressings. Cellulose-based metallogels can be used in the food packaging industry to provide biodegradable and biocidal materials to extend the shelf life of the goods. Metal and bimetallic nanoparticles (Au, Cu, Ni, AuAg, and AuPt) can catalyze chemical reactions, enabling composite cellulose hydrogels to be used as efficient catalysts in organic synthesis. In addition, metal-loaded hydrogels (with ZnO, TiO₂, Ag, and Fe₃O₄ nanoparticles) can exhibit enhanced adsorption capacities for pollutants, such as dyes, heavy metal ions, and pharmaceuticals, making them valuable materials for water purification and environmental remediation. Magnetic properties imparted to metallogels by iron oxides (Fe₂O₃ and Fe₃O₄) simplify the wastewater treatment process, making it more cost-effective and environmentally friendly. The conductivity of metallogels due to Ag, TiO₂, ZnO, and Al₂O₃ is useful for the design of various sensors. The integration of metal nanoparticles also allows the development of responsive materials, where changes in metal properties can be exploited for stimuli-responsive applications, such as controlled release systems. Overall, the introduction of metal phases augments the functionality of cellulose hydrogels, expanding their versatility for diverse applications across a broad spectrum of industries not envisaged during the initial research stages. Full article