Convalescent Plasma for Critically-ill Covid-19 Patients (preprint)

Background and aim: Convalescent plasma (CP) was early and successfully used in management of covid-19 infection. This report aimed to document our experience with use of CP in two critically-ill covid-19 patients.Main findings: Patients presented with fever, dry cough and difficulty of breathing with reduced oxygen saturation, massive radiological lung involvement and deteriorated Sequential Organ Failure Assessment (SOFA) Score. Use of two sessions of CP resulted in marked improvement of radiological and/or pulmonary findings. Both patients died of septic shock or thromboembolic events.Conclusions Use of CP may be associated with radiological and clinical improvement in critically-ill patients. However, it’s not related to better survival if used in late stages of the disease.

Role of authentic leadership in enhancing employees' voice behavior through psychological capital during COVID-19 pandemic

Purpose: Considering the importance of employees' voice behavior (VB) and psychological capital (PC) amidst the coronavirus disease 2019 (COVID-19), this study highlights the role of authentic leadership (AL) in building a psychologically strong workforce that can provide meaningful suggestions for the improvement of organization. Design/methodology/approach: The study employed a questionnaire survey to collect the data and recruited 261 participants from the telecom sector Sindh, Pakistan. The data analysis was done using partial least squares structural equation modeling (PLS-SEM). Findings: The findings of the study supported the hypotheses suggesting that AL can directly influence employees' VB and indirectly via PC. Originality/value: The study was conducted during the COVID-19 in the telecom sector of Sindh, Pakistan. This study contributes by providing useful insights into that AL is an important form of leadership that encourages employees' voluntary behavior and psychological strength during the COVID-19 pandemic. © 2023, Emerald Publishing Limited.

Eye Sight - A Bull's Eye Target of COVID-19

Aim: To determine the effect of COVID-19 on eye sight due to increase screen time in undergraduate students of medical school. Study design: Cross-sectional study. Place and duration of study: This survey was carried out from October 2022 to December 2022 in Army Medical College Rawalpindi. Questionnaires were filled in person and also online-based platform was used to distribute the e-questionnaire, developed using the Google Form. The participants were asked to share the e-questionnaire with their friends using Facebook and Messenger. Method(s): Participants were selected for the study using non-probability consecutive sampling. College students of 20-25 years were included in the study. Sample size was 400 according to a study done internationally. Participants with comorbidities (cataract, glaucoma) were excluded from study. Participants having (trouble concentrating on things such as reading the newspaper, books or watching television) were included in the study. Digital eye strain was calculated using validated computer vision syndrome (CVS-Q) questionnaire to measure the symptoms such as eye fatigue, headache, blurred vision, double vision, itching eyes, dryness, tears, eye redness and pain, excessive blinking, feeling of a foreign body, burning or irritation, difficulty in focusing for near vision, feeling of sight worsening, and sensitivity to light. Qualitative data was analyzed using Chi square test. Results A total number of 470 responses were recorded, out of which 257 (54.7%) were males and 213(45.3%) were females. In our study, the most common symptom was headache, affecting 58.1% of the population before COVID 19 which has increased to 83.2% and the P value is less than 0.001.Theother symptoms which also showed P value less than 0.001 were blurred vision while using digital device, irritated or burning eyes, dry eyes and sensitivity to bright light. Conclusion The practical implication of the study is to create awareness among general population about COVID, that eye sight is Bull`s Target to be affected by it and simple preventing measures can be taken. The purpose of this study is to limelight the importance that during COVID 19 lockdown the excessive use of digital devices and their cons on the ocular health among future health care workers.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Deferoxamine in the management of COVID-19 adult patients admitted to ICU: a prospective observational cohort study.

COVID-19 infection is associated with high mortality, and despite extensive studying the scientific society is still working to find a definitive treatment. Some experts postulated a beneficial role of Deferoxamine. Aim: The aim of this study was to compare the outcomes of COVID-19 adult patients admitted to the ICU who received deferoxamine to those who received standard of care. Methods: Prospective observational cohort study, in the ICU of a tertiary referral hospital in Saudi Arabia to compare all-cause hospital mortality between COVID-19 patients who received deferoxamine and standard of care. Results: A total of 205 patients were enrolled, with an average age of 50.1±14.3, 150 patients received standard of care only, and 55 patients received deferoxamine additionally. Hospital mortality was lower in deferoxamine group (25.5 vs. 40.7%, 95% CI=1.3-29.2%; P=0.045). Clinical status score upon discharge was lower in deferoxamine group (3.6±4.3 vs. 6.2±4, 95% CI: 1.4-3.9; P<0.001), as was the difference between discharge score and admission score (indicating clinical improvement). More patients admitted with mechanical ventilation were successfully extubated in the deferoxamine group (61.5 vs. 14.3%, 95% CI: 15-73%; P=0.001), with a higher median ventilator-free days. There were no differences between groups in adverse events. Deferoxamine group was associated with hospital mortality [odds ratio=0.46 (95% CI: 0.22-0.95); P=0.04]. Conclusions: Deferoxamine may have mortality and clinical improvement benefits in COVID-19 adults admitted to ICU. Further powered and controlled studies are required.

Epstein-Barr virus and cytomegalovirus coinfection in Egyptian COVID-19 patients.

Background: Reactivation of herpesviruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in COVID-19 patients reported in many studies in different countries during the pandemic. We aimed to measure prevalence of this coinfection in Egyptian COVID-19 patients with elevated liver enzymes and its relation to the severity and the outcome of COVID-19 infection in those patients. Methods: A cross-sectional study was carried out on 110 COVID-19 patients with elevated liver enzymes regardless the severity of COVID-19 disease. All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest). Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) were determined by VCA IgM and CMV IgM respectively by enzyme-linked immunosorbent assay (ELISA). Results: Of the included 110 patients with COVID-19 illness, 5 (4.5%) were Epstein-Barr virus seropositive and 5 (4.5%) were human cytomegalovirus seropositive. Regarding the symptoms, the incidence of fever in the EBV and CMV seropositive group was apparently higher than that in the EBV and CMV seronegative group. In lab tests, the platelets and albumin of EBV and CMV seropositive group decreased more significantly than EBV and HCMV seronegative group, and serum ferritin, D-dimer, and C-reactive protein show higher values in seropositive group than in seronegative group but not statistically significant. Seropositive group had received higher doses of steroids than seronegative group. The median of hospital stay in seropositive group was (15 days) nearly double that of seronegative group with statistically significant difference between both groups. Conclusion: Coinfection of EBV and CMV in COVID-19 Egyptian has no effect on the disease severity or the clinical outcome of the disease. But those patients had higher hospital stay duration.

Prediction of the SARS-CoV-2 Derived T-Cell Epitopes' Response against COVID Variants

The COVID-19 outbreak began in December 2019 and was declared a global health emergency by the World Health Organization. The four most dominating variants are Beta, Gamma, Delta, and Omicron. After the administration of vaccine doses, an eminent decline in new cases has been observed. The COVID-19 vaccine induces neutralizing antibodies and T-cells in our bodies. However, strong variants like Delta and Omicron tend to escape these neutralizing antibodies elicited by COVID-19 vaccination. Therefore, it is indispensable to study, analyze and most importantly, predict the response of SARS-CoV-2-derived t-cell epitopes against Covid variants in vaccinated and unvaccinated persons. In this regard, machine learning can be effectively utilized for predicting the response of COVID-derived t-cell epitopes. In this study, prediction of T-cells Epitopes' response was conducted for vaccinated and unvaccinated people for Beta, Gamma, Delta, and Omicron variants. The dataset was divided into two classes, i.e., vaccinated and unvaccinated, and the predicted response of T-cell Epitopes was divided into three categories, i.e., Strong, Impaired, and Over-activated. For the aforementioned prediction purposes, a self-proposed Bayesian neural network has been designed by combining variational inference and flow normalization optimizers. Furthermore, the Hidden Markov Model has also been trained on the same dataset to compare the results of the self-proposed Bayesian neural network with this state-of-the-art statistical approach. Extensive experimentation and results demonstrate the efficacy of the proposed network in terms of accurate prediction and reduced error. © 2023 Tech Science Press. All rights reserved.

Atypical clinical features of post COVID-19 mucormycosis: A case series.

OBJECTIVES: This case series aims to evaluate patients affected with post COVID-19 mucormycosis from clinical presentation to surgical and pharmacological treatment to improve the disease prognosis. MATERIAL AND METHODS: This case series was conducted at a specialized surgery hospital in Baghdad Medical City for over 10 months. Fifteen cases who had mild to severe COVID-19 infections followed by symptoms similar to aggressive periodontitis, such as mobility and bone resorption around the multiple maxillary teeth, were included in this case series. RESULTS: All patients did not receive COVID-19 vaccination; seven had a history of diabetes mellitus type 2, another five patients had a history of diabetes-like syndrome during the COVID-19 infection, and the remaining three patients had no history of any systemic diseases. No intracranial involvement was seen in all patients, and bilateral sinus involvement was seen in three patients. CONCLUSION: Being highly suspicious of all patients affected with COVID-19 is highly recommended to avoid the complications of the late diagnosis of mucormycosis. In addition, our knowledge and methods in diagnosing and treating classical mucormycosis should be modified regarding post COVID-19 mucormycosis.

Zika Virus Vaccine: The Current State of Affairs and Challenges Posed by Antibody-Dependent Enhancement Reaction.

Infection caused by the Zika virus (ZIKV) can lead to serious neurological complications such as microcephaly in neonates. At present, no approved ZIKV vaccine is available, but few vaccine candidates are undergoing clinical trial. One major challenge faced is antibody-dependent enhancement (ADE) reaction that may provoke severe outcome in subsequent infection by ZIKV or other flaviviruses. Thus, more efforts should be dedicated to understanding ADE in designing a safe and effective vaccine to minimize the consequence of the potentially fatal infection's complications and to tackle potential ZIKV reemergence. This review discusses different types of ZIKV vaccine candidates that are currently underway in various stages of preclinical and clinical evaluations.

Long-term study on wastewater SARS-CoV-2 surveillance across United Arab Emirates.

Wastewater-based epidemiology (WBE) demonstrates an efficient tool to monitor and predict SARS-CoV-2 community distribution. Many countries across the world have adopted the technique, however, most of these studies were conducted for a short duration with a limited sampling size. In this study, long-term reliability and quantification of wastewater SARS-CoV-2 surveillance is reported via analyzing 16,858 samples collected from 453 different locations across the United Arab Emirates (UAE) from May 2020 to June 2022. The collected composite samples were first incubated at 60 °C followed by filtration, concentration, and then RNA extraction using commercially available kits. The extracted RNA was then analyzed by one-step RT-qPCR and RT-ddPCR, and the data was compared to the reported clinical cases. The average positivity rate in the wastewater samples was found to be 60.61 % (8.41-96.77 %), however, the positivity rate obtained from the RT-ddPCR was significantly higher than the RT-qPCR suggesting higher sensitivity of RT-ddPCR. Time-lagged correlation analysis indicated an increase in positive cases in the wastewater samples when the clinical positive cases declined suggesting that wastewater data are highly affected by the unreported asymptomatic, pre-symptomatic and recovering individuals. The weekly SARS-CoV-2 viral count in the wastewater samples are positively correlated with the diagnosed new clinical cases throughout the studied period and the studied locations. Viral count in wastewater peaked approximately one to two weeks prior to the peaks appearing in active clinical cases indicating that wastewater viral concentrations are effective in predicting clinical cases. Overall, this study further confirms the long-term sensitivity and robust approach of WBE to detect trends in SARS-CoV-2 spread and helps contribute to pandemic management.

Impact of diabetes mellitus and co-morbidities on mortality in patients with COVID-19: A single-center retrospective study.

OBJECTIVES: To describe the effect of diabetes mellitus (DM) on clinical outcomes of patients admitted with COVID-19 infection. METHODS: We carried out a single center, observational, retrospective study. We included adult patients with laboratory-confirmed diagnosis of COVID-19 admitted to a tertiary hospital in Jeddah, Saudi Arabia, from April 2020 to December 2020. Electronic medical records were reviewed for demographics, clinical status, hospital course, and outcome; and they were compared between the patients with or without DM. RESULTS: Out of 198 patients included in the study, 86 (43.4%) were diabetic and 112 (56.5%) were non-diabetic. Majority of the patients were males 139 (70.2%) with a mean age of 54.14±14.89 years. In-hospital mortality rate was higher in diabetic patients than in non-diabetic patients (40 vs. 32; p=0.011). The most common comorbidity was hypertension (n=95, 48%) followed by ischemic heart disease (n=35, 17.7%), chronic kidney disease (n=17, 9.6%), and bronchial asthma (n=10, 5.1%). CONCLUSION: The risk of SARS-CoV-2 infection is higher among diabetic patients; particularly, those with preexisting co-morbidities or geriatric patients. Diabetic patients are prone to a severe clinical course of COVID-19 and a significantly higher mortality rate.

Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation

Background: Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations. The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses high risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined. Purpose(s): To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates. Method(s): A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights. Result(s): Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF <50% 78%/ 66% for DHFP/ SoC, respectively. 196 high risk transmissions prompted telephone assessment, with successful contact in 182;of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results. Conclusion(s): This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes. (Figure Presented) .

Covid severity prediction: Who cares about the data quality?

COVID-19 is an ongoing pandemic disrupting daily life and overwhelming the healthcare infrastructure. Since the outburst of the pandemic, researchers have used various techniques to predict many aspects of the disease, including mortality rate and severity. The reproducibility of this research is challenging due to varying methodologies used to collect data, data quality, vague description of methodological approach to training prediction models, over-relying on data imputation, and over-fitting. This paper focuses on these challenges and provides a short yet comprehensive review of research on COVID mortality and severity prediction. The emphasis is on the reproducibility of the results and data quality issues. To further elaborate on the issue, we report the development of severity prediction models using two data sets. CRISP-DM is used as a methodological approach. We analyze and criticize the quality of the used data sets and how they affect the performance and limitations of the trained models. We conclude this paper with comments on data quality issues, the importance of reproducibility, and suggestions to improve reproducibility. © 2022 IEEE.

Mobile Application for Board of Nutrition-Dietetics and Professional Regulation Commission (PRC) Accreditation Process

The onset of the COVID-19 pandemic delayed certain operations and paved the way to strict travel restrictions. This also meant that the traditional face-to-face process for accreditation inspection was affected. With this, to adapt to the situation, many institutions switched to relying on technology. This study aims to address the digitalization of the Professional Regulation Commission of the Philippines' monitoring and accreditation system. Hence, the objective of the study is to develop an effective digital system for the Professional Regulation Commission of the Philippines. The Agile Development Lifecycle will be implemented in constructing the system. Mobile Application Test and Performance Test are tests designed to evaluate the system's capabilities and usefulness. The outcomes met the study's goal, which led to the tests being successful. © 2022 ACM.

Effect of Tocilizumab on "Ventilator Free Days" Composite Outcome in SARS-CoV-2 Patients: A Retrospective Competing Risk Analysis.

Background: SARS-CoV-2 infection demonstrates a wide range of severity. More severe cases demonstrate a cytokine storm with elevated serum interleukin-6, hence IL-6 receptor antibody tocilizumab was tried for the management of severe cases. Aims: Effect of tocilizumab on ventilator-free days among critically ill SARS-CoV-2 patients. Method: Retrospective propensity score matching study, comparing mechanically ventilated patients who received tocilizumab to a control group. Results: 29 patients in the intervention group were compared to 29 controls. Matched groups were similar. Ventilator-free days were more numerous in the intervention group (SHR 2.7, 95% CI: 1.2 - 6.3; p = 0.02), ICU mortality rate was not different (37.9% versus 62%, p = 0.1), actual ventilator-free periods were significantly longer in tocilizumab group (mean difference 4.7 days; p = 0.02). Sensitivity analysis showed a significantly lower hazard ratio of death in tocilizumab group (HR 0.49, 95% CI: 0.25 - 0.97; p = 0.04). There was no difference in positive cultures among groups (55.2% in tocilizumab group versus 34.5% in the control; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator-free days at day 28 among mechanically ventilated SARS-CoV-2 patients; it is associated with significantly longer actual ventilator-free periods, and insignificantly lower mortality and higher superinfection.

Radical reform of the undergraduate medical education program in a developing country: the Egyptian experience.

Medical educators are in a continuous quest to close the gap between the needs of medical practice and the rising expectations of the communities in their countries. During the past two decades, competency-based medical education has been evolving as an appealing strategy to close this gap. In 2017, the Egyptian medical education authorities mandated all medical schools to change their curricula to comply with revised national academic reference standards, which changed from outcome-based to competency-based. In parallel, they also changed the timeline of all medical programs for six years of studentship and one-year internship to five years and two years, respectively. This substantial reform involved the assessment of the existing situation, an awareness campaign for the proposed changes and an extensive national faculty development program. Monitoring the implementation of this substantial reform was performed through surveys, field visits and meetings with students, teaching staff and program directors. In addition to the expected challenges, the COVID-19-associated restrictions presented a significant further challenge during the implementation of this reform. This article presents the rationale for and steps of this reform, the challenges faced and how they were addressed.

Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation

Background: Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations.The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses "high” risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined. Purpose: To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates. Methods: A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights. Results: Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF <50% 78%/ 66% for DHFP/ SoC, respectively.196 high risk transmissions prompted telephone assessment, with successful contact in 182;of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results. Conclusions: This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes. Funding Acknowledgement: Type of funding sources: Private company. Main funding source(s): MedtronicFigure 1. Pathway OverviewFigure 2. Outcomes

e-REC Capturing The Occurrence and Burden Of COVID-19 Infections In People With Rare Genetic Obesity Disorders

Introduction: Following the onset of the COVID-19 pandemic in spring 2020, the European Registries For Rare Endocrine Conditions (EuRRECa), which is a collaboration between Endo- ERN, ESPE and ESE provided the possibility for registration of cases. Obesity is a risk factor for severe COVID-19 disease course in adults. In children and adolescents, COVID-19 disease course is much milder, but has also been identified as risk factor. As rare genetic obesity disorders often present with extreme obesity early in life, it might be postulated that they are at increased risk for severe course of COVID-19 infection. The aim was to study the clinical course of COVID-19 infection in these patients. Method(s): The RareEndoERN COVID-19 taskforce, formed in April 2020, set up the monthly e-REC reporting of new clinical encounters of confirmed or suspected COVID-19 cases in rare genetic obesity disorders. Thirteen centres committed to reporting. Case specific data were collected by an additional digital survey. Result(s): Seventeen patients with rare genetic obesity disorders and COVID-19 infection were reported by two centers between April 2020 and December 2021. Median age was 16 years (range min 2 - max 22), 11/17 were female, median BMI was 28kg/m2 (min 17-max 73). Diagnosis was: rare genetic obesity- syndromal form in 13/17 cases (of which 8 Prader-Willi Syndrome (PWS) and 5 other forms of syndromal obesity);non-syndromal form in 2/17;and 'other' in 2/17 patients. The following co-morbidities were present: type2 DM in 3/17, dyslipidemia 2/17, NAFLD 2/17, sleep apnoea 1/17;COVID-19 was confirmed in all cases. Symptoms were Fever (5/17);Cough (3/17);Tiredness or exhaustion (2/17);Loss of appetite (1/17);Loss of taste or smell (0/17);Muscle pain (0/17);Runny nose (3/17);Headache (4/17);Sore throat (4/17);Stomach symptoms (1/17);Diarrhoea (0/17);None (/17)2;Other (3/17) like change of behavior or seizure. One patient with PWS was admitted to the emergency room due to a seizure and was dismissed after a few hours of observation. None of the patients needed admission to the hospital, IC unit care, or oxygen treatment;18/17 patients fully recovered, 1 PWS patient had persistent complaints of tiredness. Conclusion(s): In patients with rare genetic obesity disorders and confirmed COVID-19 infection reported number of cases are low, even in large centers of expertise. The clinical course seems mild for these patients, in the age range 2-22 years, even in the presence of extreme obesity and type 2 diabetes.

Students' Satisfaction with Online Learning Environments - Post COVID-19

With the outbreak of COVID-19, several countries have requested the closure of all educational institutions;many universities have shifted to online mode during this period. Previous studies showed the need for a continuous assessment of student's satisfaction with the online delivery methods to improve the teaching and learning experience. This paper is framed with the motivational needs and social presence theories to review students' perceptions of various online learning environment tools, social presence, and satisfaction with online courses. 846 students in higher education institutes from different backgrounds and cultures participated in the online survey. Results show that the learning environment has a positive, substantial, and significant relationship with social presence. Moreover, factors influencing the learning environment that was significant to student satisfaction are presented. © 2022 IEEE.

Integration of LC/MS, NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti-SARS-CoV-2 Activity.

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC50 8.231±0.04 µg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.