A meta‐analysis was performed to identify patients with coronavirus disease 2019 (COVID‐19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random‐effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup‐analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta‐analysis suggests an association between GI symptoms in COVID‐19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID‐19 patients during the second wave compared to the first wave of the outbreak.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a resistant staph bacterium to several antibiotics causing several lives-threating diseases such as pneumonia and sepsis. Meswak, Salvadora persica, exhibited promising antimicrobial properties before. Objective: Exploring the anti-MRSA activity of S. persica L. metabolites and its mechanism of action on a molecular level. Materials and Methods: Structure elucidation of the isolated metabolites was carried out by spectroscopic data (one-dimensional and two-dimensional nuclear magnetic resonance). The biological activities of the isolated metabolites against MRSA were evaluated and the molecular mode of action against the dehydrosqualene synthase enzyme have been done. Results: Four compounds have been isolated and identifies to be; apigenin (1), luteolin (2), astragalin (3), and kaempferol-3-O-rhamnoside (4). Compounds 1–4 showed good anti-MRSA activities with IC₅₀ values of 10.3, 11.5, 3.5, and 4.5 μg/mL, respectively. In consistent, astragalin and kaempferol-3 rhamnoside showed close high docking scores. Herein, we are reporting the molecular determinates of activity of these new scaffolds as anti-MRSA, which would be of great importance to developing new anti-MRSA candidates. Abbreviations Used: 1D: One-dimensional; 2D: Two-dimensional; CC: Column chromatography; COSY: Correlations spectroscopy; DMSO: Dimethyl sulfoxide; HMBC: Heteronuclear multiple-bond correlation experiment; HRESIMS: High-resolution electrospray ionization mass spectrometry; HSQC: Heteronuclear single-quantum correlation; IR: Infrared; MRSA: Methicillin-resistant Staphylococcus aureus; NMR: Nuclear magnetic resonance; RP: Reversed phase; TLC: Thin-layer chromatography; UV: Ultraviolet; VLC: Vacuum liquid chromatography.

Bio-guided isolation from the Red Sea-derived Penicillium chrysogenum yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol (6) and chrysogenotoxin (7), alongside five known compounds: emodin (1), chrysophanol (2), bis(2-ethylhexyl) phthalate (3), haenamindole (4), and citreorosein (5). Compound 6 exhibited broad-spectrum antibacterial activity against both Gram-positive (MIC: 0.31-0.62 μM; MBC: 0.31-0.62 μM) and Gram-negative bacteria (MIC: 0.15-1.25 μM; MBC: 0.62-2.5 μM). Compound 7 showed potent bactericidal activity against Gram-negative bacteria (MIC: 0.07-0.31 μM; MBC: 0.15-0.62 μM) with MBC/MIC ≤ 4, while compound 4 selectively inhibited S. pneumoniae (MIC: 0.31 μM; MBC: 0.62 μM). Compounds 4, 6, and 7 exhibited low cytotoxicity towards human intestinal epithelial cells (HIEC-6). Molecular docking studies targeting the NDM-1 β-lactamase identified compounds 4, 6, and 7 as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1). Molecular dynamics simulations confirmed the structural stability of 7 within the NDM-1 active site. Chrysogenotoxin (7) was suggested as a promising antibacterial candidate against antibiotic-resistant pathogens.