Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29– 39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 μg/mL for curcumin and 25 μg/mL for the nanocomposite on Huh7 but was 25.8 μg/mL and 34 μg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes’ expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.

COVID-19 is a pandemic disease caused by the SARS-CoV-2, which continues to cause global health and economic problems since emerging in China in late 2019. Until now, there are no standard antiviral treatments. Thus, several strategies were adopted to minimize virus transmission, such as social distancing, face covering protection and hand hygiene. Rhamnolipids are glycolipids produced formally by Pseudomonas aeruginosa and as biosurfactants, they were shown to have broad antimicrobial activity. In this study, we investigated the antimicrobial activity of rhamnolipids against selected multidrug resistant bacteria and SARS-CoV-2. Rhamnolipids were produced by growing Pseudomonas aeruginosa strain LeS3 in a new medium formulated from chicken carcass soup. The isolated rhamnolipids were characterized for their molecular composition, formulated into nano-micelles, and the antibacterial activity of the nano-micelles was demonstrated in vitro against both Gram-negative and Gram-positive drug resistant bacteria. In silico studies docking rhamnolipids to structural and non-structural proteins of SARS-CoV-2 was also performed. We demonstrated the efficient and specific interaction of rhamnolipids with the active sites of these proteins. Additionally, the computational studies suggested that rhamnolipids have membrane permeability activity. Thus, the obtained results indicate that SARS-CoV-2 could be another target of rhamnolipids and could find utility in the fight against COVID-19, a future perspective to be considered.

Sleep deprivation (SD) has been revealed to provoke anxiety-like behavior. Phytochemicals and nanotechnology-based interventions have emerged as promising alternatives due to their pleiotropic activity and enhanced bioavailability. Here we investigated the effect of sodium selenite, Epigallocatechin-3-gallate (EGCG), and EGCG–Selenium nanoparticles (SeNPs) on SD-provoked cortical impairment and tried to recognize the possible underlying mechanisms in addition to in silico analysis of EGCG. SD was provoked in rats utilizing a modified multiple platform model. We performed an in silico analysis of EGCG docked on Bcl2 and MMP2. Forty animals were divided into five groups of eight animals each: animals were given saline orally for 8 days (control); animals were given saline orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD); animals were given Na₂SeO₃ orally with 0.5 mg/kg/day for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/Na₂SeO₃); animals were given 100 mg/kg/day EGCG orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/EGCG); animals were given SeNPs biosynthesized using EGCG and 0.5 mg/kg/day orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/EGCG-SeNPs). Behavioral tests were performed, including the sucrose preference test and the open-field test. Neurotransmitters (norepinephrine, serotonin, and dopamine), monoamine oxidase, ACh, GABA, AChE, neurotropic and glial markers (BDNF and GFAP), as well as neuro-inflammatory, oxidative stress, and apoptotic markers were assessed. Interestingly, sodium selenite, EGCG, and EGCG-SeNP employment mitigated cognitive functions and cortical histopathological alterations in SD-subjected rats. These potential impacts elicited by sodium selenite, EGCG, and EGCG-SeNPs may be related to their impact of elucidating corticosterone increase, cortical neurotransmitter decrease, and neurotropic and glial markers alterations, while also inhibiting the inflammatory and apoptotic axis and upregulating Nrf2 antioxidant cascade. These results prove the neuroprotective potential of sodium selenite, EGCG, and EGCG-SeNPs, especially EGCG-SeNPs in sleep deprivation-subjected rats by ameliorating cortical neuroinflammation, prooxidant alterations, and apoptotic events likely caused by modulating the NOS-2/Nrf2 axis.

New antibiotics are desperately needed to overcome the societal challenges being encountered with methicillin-resistant Staphylococcus aureus (MRSA). In this study, a new tetracene derivative, named Mersaquinone (1), and the known Tetracenomycin D (2), Resistoflavin (3) and Resistomycin (4) have been isolated from the organic extract of the marine Streptomyces sp. EG1. The strain was isolated from a sediment sample collected from the North Coast of the Mediterranean Sea of Egypt. The chemical structure of Mersaquinone (1) was assigned based upon data from a diversity of spectroscopic techniques including HRESIMS, IR, 1D and 2D NMR measurements. Mersaquinone (1) showed antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 3.36 μg/mL.

This study demonstrates a novel approach for the synthesis of silver nanoparticles (AgNPs) against human liver cancer cell line (HepG2) using prodigiosin pigment isolated from Serratia marcescens. It further investigates the influence of various parameters such as initial pH, temperature, silver nitrate (AgNO3) concentration, and prodigiosin concentration on stability and optical properties of synthesized prodigiosin AgNPs. Highly stable, spherical prodigiosin-conjugated AgNPs were synthesized with a mean diameter of 9.98 nm using a rapid one-step method. The cytotoxic activity investigated in the present study indicated that prodigiosin and prodigiosin-conjugated AgNPs possessed a strong cytotoxic potency against human liver cancer. The In silico molecular docking results of prodigiosin and prodigiosin-conjugated AgNPs are congruent with the In vitro studies and these AgNPs can be considered as good inhibitors of mitogen-activated protein kinase 1 (MEK kinases). The study opened the possibility of using prodigiosin-conjugated AgNPs to increase the efficiency of liver cancer treatment.

Background: The emergence of different viral infections calls for the development of new, effective, and safe antiviral drugs. Glycyrrhiza glabra is a well-known herbal remedy possessing antiviral properties. Objective: The objective of our research was to evaluate the effectiveness of a newly developed combination of the probiotics Lactobacillus acidophilus and G. glabra root extract against two viral models, namely the DNA virus Herpes simplex virus-1 (HSV-1) and the RNA virus Vesicular Stomatitis Virus (VSV), with regards to their antiviral properties. Methodology: To examine the antiviral impacts of various treatments, we employed the MTT assay and real-time PCR methodology. Results: The findings of our study indicate that the co-administration of L. acidophilus and G. glabra resulted in a significant improvement in the survival rate of Vero cells, while also leading to a reduction in the titers of Herpes Simplex Virus Type 1 (HSV-1) and Vesicular Stomatitis Virus (VSV) in comparison to cells that were not treated. Additionally, an investigation was conducted on glycyrrhizin, the primary constituent of G. glabra extract, utilizing molecular docking techniques. The results indicated that glycyrrhizin exhibited a greater binding energy score for HSV-1 polymerase (− 22.45 kcal/mol) and VSV nucleocapsid (− 19.77 kcal/mol) in comparison to the cocrystallized ligand (− 13.31 and − 11.44 kcal/mol, respectively). Conclusions: The combination of L. acidophilus and G. glabra extract can be used to develop a new, natural antiviral agent that is safe and effective.