Imipenem is the most efficient antibiotic against Acinetobacter baumannii infection, but new research has shown that the organism has also developed resistance to this agent. A. baumannii isolates from a total of 110 clinical samples were identified by multiplex PCR. The antibacterial activity of Syzygium aromaticum multiple extracts was assessed following the GC-Mass spectra analysis. The molecular docking study was performed to investigate the binding mode of interactions of guanosine (Ethanolic extract compound) against Penicillin- binding proteins 1 and 3 of A. baumannii. Ten isolates of A. baumannii were confirmed to carry recA and iutA genes. Isolates were multidrug-resistant containing bla_TEM and Bla_SHV. The concentrations (0.04 to 0.125 mg mL⁻¹) of S. aromaticum ethanolic extract were very promising against A. baumannii isolates. Even though imipenem (0.02 mg mL⁻¹) individually showed a great bactericidal efficacy against all isolates, the in-silico study of guanosine, apioline, eugenol, and elemicin showed acceptable fitting to the binding site of the A. baumannii PBP1 and/or PBP3 with highest binding energy for guanosine between −7.1 and −8.1 kcal/mol respectively. Moreover, it formed π-stacked interactions with the residue ARG76 at 4.14 and 5.6, Å respectively. These findings might support the in vitro study and show a substantial increase in binding affinity and enhanced physicochemical characteristics compared to imipenem.

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton’s jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC₅₀), cytotoxic concentration (CC₅₀), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC₅₀ and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC₅₀ and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

Pseudomonas aeruginosa is an organism commonly found in the environment and one of the most common causes of human urinary tract infections in developed and developing countries. The present study aimed to investigate the effect of five medicinal plant extracts on the isolated drug-resistant P. aeruginosa clinical isolates. A total of 100 urine samples were collected from Nagaa Hammadi and Qena General Hospitals and private medical analysis laboratories in Qena governorate, Upper Egypt. Samples were screened for the prevalence of UTI pathogens by biochemical tests, antibiotics sensitivity, detection of virulence, and antibiotic-resistant genes by using multiplex PCR. P. aeruginosa is by far the subdominant causative agent with a percentage of 14. Clinical isolates were multidrug-resistant, containing bla_TEM, bla_SHV, toxA, lasB, pslA, and fliC resistant and virulence genes. Based on bioactivity, the ethanolic extract of clove (Syzygium aromaticum) was the most active extract among tested medicinal plants and had the maximum zone of inhibition sized 23mm against tested bacteria. The results of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) showed a high decrease of inhibition within a concentration range of (10 to 121.25mg/mL and 20 to 30mg/mL, respectively). Further, major compounds of oleic acid (27.22), guanosine (8.91), indole (6.83), 1-eicosene (6.30), and cis-10-nonadecenoic acid (5.37) were determined among 12 bioactive compounds in the ethanolic extract of S. aromaticum using gas chromatography-mass spectrometry (GC-MS). These results indicated that the ethanolic extract of S. aromaticum is a promising antibacterial agent for further studies aiming to control bacterial infections including MDR bacteria and develop novel therapeutic alternatives for the treatment of UTI.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4⁺ and CD8⁺ memory T cells’ compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8⁺ T cells and effector memory-expressing CD45RA CD8⁺ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4⁺ T cells, CD8⁺ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8⁺ TSCMs and CD4⁺ TNs cells, while female patients had a significantly higher percentage of effector CD8⁺CD45RA⁺ T cells. Moreover, altered percentages of CD8⁺ TNs and memory CD8⁺CD45RO⁺ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.