Galangal-Cinnamon Spice Mixture Blocks the Coronavirus Infection Pathway through Inhibition of SARS-CoV-2 MPro, Three HCoV-229E Targets; Quantum-Chemical Calculations Support In Vitro Evaluation.

Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal-cinnamon mixture in the inhibition of SARS-CoV-2's different protein targets. The potential antiviral effect of galangal-cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition assay and the crystal violet method. Low Pathogenic HCoV-229E was used as it is safer for in vitro laboratory experimentation and due to the conformation and the binding pockets similarity between HCoV-229E and SARS-CoV-2 MPro. The GCAE showed a significant antiviral effect against HCoV-229E (IC50 15.083 µg/mL). Twelve phenolic compounds were detected in the extract with ellagic, cinnamic, and gallic acids being the major identified phenolic acids, while rutin was the major identified flavonoid glycoside. Quantum-chemical calculations were made to find molecular properties using the DFT/B3LYP method with 6-311++G(2d,2p) basis set. Quantum-chemical values such as EHOMO, ELUMO, energy gap, ionization potential, chemical hardness, softness, and electronegativity values were calculated and discussed. Phenolic compounds detected by HPLC-DAD-UV in the GCAE were docked into the active site of 3 HCoV-229E targets (PDB IDs. 2ZU2, 6U7G, 7VN9, and 6WTT) to find the potential inhibitors that block the Coronavirus infection pathways from quantum and docking data for these compounds. There are good adaptations between the theoretical and experimental results showing that rutin has the highest activity against Low Pathogenic HCoV-229E in the GCAE extract.

Monotherapy versus polytherapy of enoxaparin and hydroxychloroquine for the treatment of COVID-19: A randomized controlled clinical trial.

Objectives: The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods: The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results: The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion: These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits.

Monotherapy versus polytherapy of enoxaparin and hydroxychloroquine for the treatment of COVID-19: A randomized controlled clinical trial

Objectives: The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods: The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results: The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion: These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits. (AU)

The Outcomes of COVID-19 Patients with Spontaneous Intracerebral Hemorrhage Comorbidity and the Efficacy of Enoxaparin in Decreasing the Mortality Rate in Them: Single Egyptian Center Report.

Patients with neurological comorbidities are more likely to develop severe COVID-19. We aimed to detect the outcomes of COVID-19 patients with spontaneous intracerebral hemorrhage comorbidity and the role of enoxaparin in decreasing the mortality rate in these cases, even though enoxaparin is a potential cause of intracerebral hemorrhage. The patients were checked on to detect surveillance outcomes, the relationship between mortality and patient characteristics, and the relationship between enoxaparin and study outcomes. Chest condition and GCS improved in 67.9% of participants. Hematoma course increased in 49.1%. Midline-shift, brain-edema, and COVID symptoms improved in 67.9%. There was a non-significant difference in mortality regarding age and gender. There was a significant difference in mortality regarding treatment with enoxaparin; 75% of the patients who did not receive enoxaparin died. 92.6% of the patients who showed decreases in hematoma course were administered enoxaparin. 76.9% of the patients who showed increases in hematoma-course were administered enoxaparin. Most of the patients who were admitted to the neurosurgical unit with spontaneous intracerebral hemorrhage acquired the COVID-19 infection. Most of the cases included in this study did not progress to severe cases. The dying patients showed deterioration in both neurological and COVID-19 symptoms. The anticoagulant properties of enoxaparin given earlier before and throughout the infection can considerably reduce mortality in COVID-19 individuals with spontaneous intracerebral hemorrhage. It is recommended to use enoxaparin for cases with spontaneous intracerebral hemorrhage and COVID-19 regardless of hematoma size because the rate of improvement was greater than the mortality rate after using enoxaparin in this study.

Antibiotic consumption in hospitals during COVID-19 pandemic: a comparative study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) results in similar clinical characteristics as bacterial respiratory tract infections and can potentially lead to antibiotic overuse. This study aimed to determine the changes in hospital antimicrobial usage before and during the COVID-19 pandemic. METHODOLOGY: We compared antimicrobial consumption data for 2019 and 2020. Inpatient antibiotic consumption was determined and expressed as a defined daily dose (DDD) per 100 occupied bed days, following the World Health Organization (WHO) methods. The WHO Access, Watch, and Reserve (AWaRe) classification was used. RESULTS: The total antimicrobial consumption in 2020 increased by 16.3% compared to consumption in 2019. In 2020, there was a reduction in fourth-generation cephalosporins (-30%), third-generation cephalosporins (-29%), and combinations of penicillins (-23%). In contrast, antibiotics that were consumed more during 2020 compared with 2019 included linezolid (374%), vancomycin (66.6%), and carbapenem (7%). Linezolid is the only antibiotic from the Reserve group on the hospital's formulary. Antibiotic usage from the Access group was reduced by 17%, while antibiotic usage from the Watch group and the Reserve group was increased by 3% and 374%, respectively. CONCLUSIONS: The findings show a significant shift in antibiotic usage from the Access group to the Watch and Reserve groups. The Watch and Reserve groups are known to be associated with increased resistance to antibiotics. Therefore, antimicrobial stewardship should be increased and maintained during the pandemic to ensure appropriate antibiotic use.

Isatin Counteracts Diethylnitrosamine/2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Male Wistar Rats by Upregulating Anti-Inflammatory, Antioxidant, and Detoxification Pathways.

Hepatocellular carcinoma (HCC) represents around 85% of all known types of liver cancers and is estimated to be the fifth most common cause of cancer-related death worldwide. The current study assessed the preventive efficacy of isatin on diethylnitrosamine (DENA)/2-acetylaminofluorene (2-AAF)-induced hepatocarcinogenesis in male Wistar rats and investigated the underlying cellular and molecular mechanisms. HCC was initiated by intraperitoneal injection of DENA (150 mg/kg/week) for two weeks, followed by oral 2-AAF (20 mg/kg) every other day for three successive weeks. Oral isatin or vehicle (control) was administered at 25 mg/kg for 20 weeks during and following HCC induction. Isatin ameliorated the deleterious effects of DENA/2-AAF on liver function as evidenced by reduced serum levels of AST, ALT, total bilirubin, albumin, and liver tumor biomarkers (CA19.9 and AFP) compared to control DENA/2-AAF-treated rats. Histopathological evaluations demonstrated that isatin-mediated protection against hepatocarcinogenesis was accompanied by a decline in hepatic lipid peroxidation, a marker of oxidative stress, and enhanced antioxidant capacity, as evidenced by increased glutathione and superoxide dismutase expression. Isatin treatment also upregulated expression of the major stress-response transcription factor Nrf2 and the detoxifying enzymes NAD(P)H quinine oxidoreductase and glutathione-S-transferase alpha 2 and downregulated expression of the proliferation marker Ki67. Moreover, isatin significantly reduced the DENA/2-AAF-induced decrease in hepatic expression of anti-apoptotic Bcl2 and the DENA/2-AAF-induced increases in pro-inflammatory and pro-apoptotic factors (TNF-α, NF-κB p50, NF-κB p65, p53, and caspase 3). Thus, it can be concluded that isatin may protect against chemically induced hepatocarcinogenesis by enhancing cellular antioxidant, anti-inflammatory, and detoxification mechanisms, in part through upregulation of the Nrf2 signaling pathway.

Thyme Oil and Thymol Counter Doxorubicin-Induced Hepatotoxicity via Modulation of Inflammation, Apoptosis, and Oxidative Stress.

Doxorubicin (DOX) is an effective anticancer agent with a wide spectrum of activities. However, it has many adverse effects on various organs especially on the liver. Thymol, one of the major components of thyme oil, has biological properties that include anti-inflammatory and antioxidant activities. Thus, this study was designed to examine thyme oil and thymol for their ability to prevent doxorubicin-induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced by an intraperitoneal injection of doxorubicin, at a dose of 2 mg/kg bw/week, for seven weeks. Doxorubicin-injected rats were supplemented with thyme oil and thymol at doses 250 and 100 mg/kg bw, respectively, four times/week by oral gavage for the same period. Treatment of rats with thyme oil and thymol reversed the high serum activities of AST, ALT, and ALP and total bilirubin, AFP, and CA19.9 levels, caused by doxorubicin. Thyme oil and thymol also reduced the high levels of TNF-α and the decreased levels of both albumin and IL-4. These agents ameliorated doxorubicin-induced elevation in hepatic lipid peroxidation and associated reduction in GSH content and GST and GPx activities. Further, the supplementation with thyme oil and thymol significantly augmented mRNA expression of the level of antiapoptotic protein Bcl-2 and significantly downregulated nuclear and cytoplasmic levels of the hepatic apoptotic mediator p53. Thus, thyme oil and thymol successfully counteracted doxorubicin-induced experimental hepatotoxicity via their anti-inflammatory, antioxidant, and antiapoptotic properties.

SARS-CoV-2 Post Vaccinated Adverse Effects and Efficacy in the Egyptian Population.

Vaccines are the solution to overcome SARS-CoV-2. This study aimed to determine the post-Sinopharm vaccine safety-profile and immunity through antibody titers. Data were collected using a structured questionnaire from Egyptian participants who received two doses of Sinopharm vaccine. Data were divided into three parts, the first and second parts were to detect participants' post-first and second dose symptoms and practices, and the third for the results of IgG anti spike protein antibodies test and laboratory tests. Pain, redness, swelling at the injection site, headache, fatigue, and lethargy were the most common post-vaccine symptoms for both first and second doses. Most of the participants felt mild or no symptoms after vaccination. The symptoms started mostly during the first day post-vaccination and lasted for no more than two days. Forty-nine percent of the participants resulted in positive antibodies tests on day 18 post-vaccination. The average antibody level for vaccinated participants with past SARS-CoV-2 infection was much higher than that for non-past infected participants. These vaccines' administration methods need to be reevaluated by changing the dose, dose interval, adding a third dose, or mixing it with other vaccines with different techniques to improve their protection rates. Further studies are required to validate this finding.