Folic acid–conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action Folic acid–conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic–organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19.

The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection’s spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds’ physical and chemical features, including molecular dynamic (MD) simulations, protein–ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral M^pro protein and may have emerged as a novel COVID-19 curative option.

Human adenoviruses (HAdV) are a prevalent cause of diarrhea in children all over the world. Adenoviral infections are responsible for 2% to 10% of diarrheic cases. A long-term investigation was required to gain better knowledge about the incidence of HAdV in Egypt. Herein, we conducted 5 years of detection, isolation, and genotyping of HAdV in fecal and sewage samples from 2016 to 2020, in Cairo, Egypt using molecular and cell culture assays. Human adenoviruses were identified in 35 of 447 fecal samples (7.8%), but only 53.3% (64/120) of the sewage samples. Children under the age of two had the highest positive rate for HAdV infection (77.1%). Species F of HAdV was the most common prevalent genotype in fecal and sewage samples, at 88.5% and 85.9%, respectively. The most prevalent genotypes detected in fecal samples were HAdV-41 (71.2%), HAdV-40 (17.2%), HAdV-6 (5.7%), and HAdV-1 (5.7%). In contrast, the most common genotypes in sewage samples were HAdV-41 (64%), HAdVs-40 (21.8%), HAdV-6 (7.8%), HAdV-1 (4.7%), and HAdV-2 (1.6%). HAdV was detected in all months of the year, with a peak period for clinical samples from December to February (p < 0.001), which matched Egypt’s rainy season, while the monthly distribution of HAdV in sewage samples remained consistent throughout the year, with no statistically significant peak period. Interestingly, the HAdV-type 41 genotype was the most common genotype during all of the years of this study. Throughout a 5-year period, our work revealed the infection rate, seasonal distribution, virus isolates, and genetic diversity of HAdV infections in environmental and clinical samples in Cairo, Egypt. Non-enteric adenovirus types (1, 2 and 6), as well as enteric adenovirus (41 and 40), may play a key role in gastroenteritis in Egypt.

Access to safe water is essential to life and public health of human. Nearly, 884 million people about one-sixth of the world’s populations are consuming contaminated water. In this study, the occurrence and the molecular characterization of enteric viruses particularly; enteric adenovirus, rotavirus and free-living protozoan Acanthamoeba spp. were determined in 180 tap water samples collected from five Egyptian governorates during December 2016 to November 2017. Moreover, we aimed to verify whether these isolated Acanthamoeba spp. could play a role in transmission of enteric adenovirusand rotavirus. Multiplex semi-nested RT-PCR, PCR and sequencing were used to detect and genotype rotavirus, enteric adenovirus and Acanthamoeba. Based on the sequence analysis of the Diagnostic Fragment 3 (DF3) of small subunit rRNA gene, Acanthamoeba isolates were genotyped. The present study showed that 26.7% (48/180) of tap water samples were positive for Acanthamoeba spp. The highest occurrence rate of Acanthamoeba (36.1%) was detected in tap water samples collected from Faiyum governorate. On the other hand, viral genomes were detected in 44 samples. Rotavirusand enteric adenoviruswere observed in 15.6% (28/180) and 8.9% (16/180) of samples, respectively. Qalyubia and Faiyum governorates showed high level of viral contamination up to 50% (18/36) and 47.2% (17/36), respectively. Winter was the peak season for viral and Acanthamoeba contamination in tap water. Mixed contamination between at least one virus and Acanthamoeba was observed. Acanthamoeba lenticulata, Acanthamoeba T4, rotavirusG1P [8], and human enteric adenovirus41 were the most predominant types identified during this work. The prevalence of pathogenic Acanthamoeba genotypes, especially genotype T4 and enteric viruses (rotavirusand adenovirus) in the examined tap water samples presented health hazards to consumers.