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In this paper, we discuss the influence of the ligand type present on the surface of silver nanoparticles (AgNPs) on its affinity to the virus surface and its virucidal activity against herpes simplex virus type 2 (HSV-2). We selected four different ligands, which potentially exhibit different affinity to the HSV-2 virus surface and used them for functionalization of AgNPs: i) sodium citrate: ii) tannic acid; iii) 1-mercaptoundecane-1-sulfonate (MUS); iv) and poly(ethylene glycol) (PEG). The antiviral activity was performed by in vitro Vero cell culture. Anti- inflammatory activity was performed by measurement of NF-κB activity. The antiviral potential of functional NPs in vivo was tested with HSV-2 model of genital infection. Cryo- transmission electron microscopy (cryo-TEM) was used to directly visualize the interactions or lack of interactions of functional NPs with the surface of the HSV-2 virus and to assess their affinity for the virus surface. It was found that the surface chemistry of NPs plays a key role in modulation of its interaction with the HSV-2 virus. Two of the selected ligands (sodium citrate and PEG) were inert and show no affinity to the virus surface. AgNPs functionalized with heparan sulfate-mimic ligand (MUS) showed high affinity to the virus surface, and the appearance of these interactions resulted in virus deactivation in about 50%. In the case of silver nanoparticles functionalized with tannic acid, the assessment of the affinity is difficult to be resolved, mainly because TA-AgNPs exhibit very strong virucidal effect (~100%) and immediately after the contact of the HSV-2 virus with those NPs the virus structure is being destroyed. The obtained results indicate that the high affinity of functional nanoparticles to the virus surface does not provide the high virucidal effectiveness. The most effective revealed to be TA-AgNPs which exhibit very strong virucidal effect against HSV-2 virus.

Todays, nano-pharmaceutics is emerging as an important field of science to develop and improve efficacy of different drugs. Although nutraceuticals are currently being utilized in the prevention and treatment of various chronic diseases such as cancers, a number of them have displayed issues associated with their solubility, bioavailability, and bio-degradability. In the present review, we focus on curcumin, an important and widely used polyphenol, with diverse pharmacological activities such as anti-inflammatory, anti-carcinogenic, anti-viral, etc. Notwithstanding, it also exhibits poor solubility and bioavailability that may compromise its clinical application to a great extent. Therefore, the manipulation and encapsulation of curcumin into a nanocarrier formulation can overcome these major drawbacks and potentially may lead to a far superior therapeutic efficacy. Among different types of nanocarriers, biological and biopolymer carriers have attracted a significant attention due to their pleiotropic features. Thus, in the present review, the potential protective and therapeutic applications of curcumin, as well as different types of bio-nanocarriers, which can be used to deliver curcumin effectively to the different target sites will be discussed.

Background Nanotechnology has been recognized as a viable technology for enhancing agriculture, particularly in the plant pathogen management area. Alfalfa mosaic virus (AMV) is a global pathogen that affects many plant species, especially economically valuable crops. Currently, there is less data on the interaction of nanoparticles with phytopathogens, particularly viruses. The current study looked into how copper oxide nanoparticles (CuO-NPs)-mediated Haloxylon salicornicum aqueous extract can fight AMV infections on tobacco plants. Results Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses showed that CuO-NPs have a spherical and hexagonal structure ranging from 20 to 70 nm in size. Fourier transform infrared spectroscopy (FTIR) analysis showed that the produced CuO-NPs have many functional groups and a lot of secondary plant metabolites. Under greenhouse conditions, the foliar application of CuO-NPs (100 ppm) enhanced tobacco growth and decreased viral symptoms. Treatment with CuO-NPs 48 h before (protective treatment) or 48 h after (curative treatment) AMV infection significantly reduced AMV accumulation levels by 97%. Additionally, the levels of total chlorophyll, phenolic, and flavonoid contents, as well as DPPH, exhibited a significant increase in tobacco leaves 30 days after inoculation in comparison to untreated plants. Moreover, considerable differences in levels of different antioxidant enzymes, including SOD, PPO, POX, and CAT, were also observed. On the other hand, the oxidative stress markers (MDA and H 2 O 2 ) were significantly reduced in CuO-NPs-treated plants compared with non-treated plants. It was also found that the protective treatment increased the expression levels of genes involved in the jasmonic pathway ( JERF3 and WRKY1 ). On the other hand, the curative treatment increased the expression levels of polyphenolic pathway acid ( CHI and HQT ) and the SA-signaling pathway genes ( PR-2 and POD ). The study of molecular docking interactions with four AMV target proteins showed that CuO-NPs had high binding energy with the viral replication protein 1a, measured at -3.2 kcal/mol. The binding with these proteins can suppress AMV replication and spread, potentially clarifying the mechanism behind the antiviral effect. Conclusions The overall analysis results indicate that the curative treatment is more influential and successful than the protective treatment in combating AMV infection. Consequentially, CuO-NPs could potentially be employed in foliar sprays for the effective and environmentally friendly management of plant virus infections.

Plant-derived exosome-like nanoparticles (PELNs) are a type of membranous vesicle isolated from plant tissues. They contain proteins, lipids, nucleic acids, and other components. PELNs are involved in the defensive response to pathogen attacks by exerting anti-inflammatory, antiviral, antifibrotic, and antitumor effects through the substances they contain. Most PELNs are edible and can be used as carriers for delivering specific drugs without toxicity and side effects, making them a hot topic of research. Sources of PELNs are abundantly, and they can be produced in high yields, with a low risk of developing immunogenicity in vivo. This paper summarizes the formation, isolation, and purification methods; physical properties; and composition of PELNs through a comprehensive literature search. It also analyzes the biomedical applications of PELNs, as well as future research directions. This paper provides new ideas and methods for future research on PELNs.

The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy. Keywords: N-acetylcysteine, SARS-CoV-2; COVID-19, coronavirus, repurposing approved drugs, engineering nanoparticles, virus infected cells, respiratory viral diseases, antioxidant, glutathione, T lymphocytes, immune modulating activity, anti-inflammatory response, antiviral effect, clinical translation

Fucoidan is a heterogeneous group of polysaccharides isolated from marine organisms, including brown algae and marine invertebrates. The physicochemical characteristics and potential bioactivities of fucoidan have attracted substantial interest in pharmaceutical industries in the past few decades. These polysaccharides are characterized by possessing sulfate ester groups that impart negatively charged surfaces, low/high molecular weight, and water solubility. In addition, various promising bioactivities have been reported, such as antitumor, immunomodulatory, and antiviral effects. Hence, the formulation of fucoidan has been investigated in the past few years in diverse pharmaceutical dosage forms to be able to reach their site of action effectively. Moreover, they can act as carriers for various drugs in value-added drug delivery systems. The current work highlights the attractive biopharmaceutical properties of fucoidan being formulated in oral, inhalable, topical, injectable, and other advanced formulations treating life-quality-affecting diseases. Therefore, the present work points out the current status of fucoidan pharmaceutical formulations for future research transferring their application from in vitro and in vivo studies to clinical application and market availability.

Favipiravir (FP) and ebselen (EB) belong to a diverse class of antiviral drugs known for their significant efficacy in treating various viral infections. Utilizing molecular dynamics (MD) simulations, machine learning, and van der Waals density functional theory, we accurately elucidate the binding properties of these antiviral drugs on a phosphorene single-layer. To further investigate these characteristics, this study employs four distinct machine learning models—Random Forest, Gradient Boosting, XGBoost, and CatBoost. The Hamiltonian of antiviral molecules within a monolayer of phosphorene is appropriately trained. The key aspect of utilizing machine learning (ML) in drug design revolves around training models that are efficient and precise in approximating density functional theory (DFT). Furthermore, the study employs SHAP (SHapley Additive exPlanations) to elucidate model predictions, providing insights into the contribution of each feature. To explore the interaction characteristics and thermodynamic properties of the hybrid drug, we employ molecular dynamics and DFT calculations in a vacuum interface. Our findings suggest that this functionalized 2D complex exhibits robust thermostability, indicating its potential as an effective and enabled entity. The observed variations in free energy at different surface charges and temperatures suggest the adsorption potential of FP and EB molecules from the surrounding environment.

Biosynthesis of silver nanoparticles (AgNPs) from marine actinobacteria offers a promising avenue for exploring bacterial extracts as reducing and stabilizing agents. We report extracellular extracts of Rhodococcus rhodochrous (MOSEL-ME29) and Streptomyces sp. (MOSEL-ME28), identified by 16S rRNA gene sequencing for synthesis of AgNPs. Ultrafine silver nanoparticles were biosynthesized using the extracts of R. rhodochrous and Streptomyces sp. and their possible therapeutic applications were studied. The physicochemical properties of nanoparticles were established by HR-SEM/TEM, SAED, UV–Vis, EDS, XRD, and FTIR. UV–Vis spectra displayed characteristic absorption at 430 nm and 412 nm for AgNPs from Streptomyces sp. (S-AgNPs) and Rhodococcus sp. (R-AgNPs), respectively. HR-SEM/TEM, XRD, EDS analysis confirmed the spherical shape, crystalline nature, and elemental formation of silver. Crystallite or grain size was deduced as 5.52 nm for R-AgNPs and 35 nm for S-AgNPs. Zeta-potential indicated electrostatic negative charge for AgNPs, while FTIR revealed the presence of diverse functional groups. Disc diffusion assay indicated the broad-spectrum antibacterial potential of S-AgNPs with the maximum inhibition of B. subtilis while R-AgNPs revealed potency against P. aeruginosa at 10 µg/mL concentration. Biogenic AgNPs revealed antileishmanial activity and the IC50 was calculated as 164 µg/mL and 184 µg/mL for R-AgNPs and S-AgNPs respectively. Similarly, the R-AgNPs and S-AgNPs revealed anti-cancer potential against HepG2 and the IC50 was calculated as 49 µg/mL and 69 µg/mL for R-AgNPs and S-AgNPs, respectively. Moreover, the antioxidant activity showed significant results. MTT assay on RD cells, L20B cells, and Hep-2C indicated intensification in viability by reducing the concentration of R-AgNPs and S-AgNPs. The R-AgNPs and S-AgNPs inhibited sabin-like poliovirus (1TCID50 infection in RD cells). Furthermore, hemocompatibility at low concentrations has been confirmed. Hence, it is concluded that biogenic-AgNPs has the potential to be used in diverse biological applications and that the marine actinobacteria are an excellent resource for fabrication of AgNPs.

Background Tobacco mosaic virus (TMV) is a highly infectious plant virus that affects a wide variety of plants and reduces crop yields around the world. Here, we assessed the effectiveness of using Ammi visnaga aqueous seed extract to synthesize silver nanoparticles (Ag-NPs) and their potential to combat TMV. Different techniques were used to characterize Ag-NPs, such as scanning and transmission electron microscopy (SEM, TEM), energy-dispersive X-ray spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). Results TEM demonstrated that the synthesized Ag-NPs had a spherical form with an average size of 23–30 nm and a zeta potential value of -15.9 mV, while FTIR revealed various functional groups involved in Ag-NP stability and capping. Interestingly, the Pre-treatment of tobacco plants (protective treatment) with Ag-NPs at 100–500 µg/mL significantly suppressed viral symptoms, while the Post-treatment (curative treatment) delayed their appearance. Furthermore, protective and curative treatments significantly increased chlorophyll a and b, total flavonoids, total soluble carbohydrates, and antioxidant enzymes activity (PPO, POX and CAT). Simultaneously, the application of Ag-NPs resulted in a decrease in levels of oxidative stress markers (H 2 O 2 and MDA). The RT-qPCR results and volcano plot analysis showed that the Ag-NPs treatments trigger and regulate the transcription of ten defense-related genes ( SbWRKY-1 , SbWRKY-2 , JERF-3 , GST-1 , POD , PR-1 , PR-2 , PR-12 , PAL-1 , and HQT-1 ). The heatmap revealed that GST-1 , the primary gene involved in anthocyanidin production, was consistently the most expressed gene across all treatments throughout the study. Analysis of the gene co-expression network revealed that SbWRKY-1 9 was the most central gene among the studied genes, followed by PR-12 and PR-2 . Conclusions Overall, the reported antiviral properties (protective and/or curative) of biosynthesized Ag-NPs against TMV lead us to recommend using Ag-NPs as a simple, stable, and eco-friendly agent in developing pest management programs against plant viral infections.

To analyze the susceptibility of SARS-CoV-2 in pregnancy and the drugs that can be used to treat pregnancy with COVID-19, so as to provide evidence for drug selection in clinic. By reviewing the existing literature, this paper analyzes the susceptibility of pregnant women to virus, especially to SARS-CoV-2, from the aspects of anatomical, reproductive endocrine and immune changes during pregnancy and screens effective and fetal-safe treatments from the existing drugs. The anatomical structure of the respiratory system is changed during pregnancy, and the virus transmitted by droplets and aerosols is more easily inhaled by pregnant women and is difficult to remove. Furthermore, the prognosis is worse after infection when compared with non-pregnancy women. And changes in reproductive hormones and immune systems during pregnancy collectively make them more susceptible to certain infections. More importantly, angiotensin-converting enzyme (ACE)-2, the SARS-CoV-2 receptor, has been proven highly increased during pregnancy, which may contribute to the susceptibility to SARS-CoV-2. When it comes to treatment, specific drugs for COVID-19 have not been found at present, and taking old drugs for new use in treating COVID-19 has become an emergency method for the pandemic. Particularly, drugs that show superior maternal and fetal safety are worthy of consideration for pregnant women with COVID-19, such as chloroquine, metformin, statins, lobinavir/ritonavir, glycyrrhizic acid, and nanoparticle-mediated drug delivery (NMDD), etc. Pregnant women are susceptible to COVID-19, and special attention should be paid to the selection of drugs that are both effective for maternal diseases and friendly to the fetus. However, there are still many deficiencies in the study of drug safety during pregnancy, and broad-spectrum, effective and fetal-safe drugs for pregnant women need to be developed so as to cope with more infectious diseases in the future.