Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics.

Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (MPRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand-target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 MPRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 MPRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 MPRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC50/IC50 = 1.33 and CC50/IC50 = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC50/IC50 = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC50/IC50 = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 MPRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19.

Are Islamic banks more resilient to the crises vis-à-vis conventional banks? Evidence from the COVID-19 shock using stock market data

The debate regarding the performance of Islamic banks vis-à-vis conventional counterparts has attracted growing attention recently. Exploiting the Covid-19 health and economic crisis as an exogenous shock, we extend this debate by examining the resilience of Islamic banks vis-à-vis conventional banks during this shock. Using data from the Gulf Cooperation Council member states, we find stock market investors have not assessed the Islamic banks to be superior to conventional ones during the Covid-19 market meltdown. Specifically, our findings show Covid-19 confirmed cases, government social distancing policies and feverish period (i.e., 24 February to 17 March 2020) have had negative impact on stock returns of both Islamic and conventional banks alike. Interestingly, the adverse impact of social distancing policies is stronger on Islamic banks due to their inherent higher cost structure. Additionally, we find the marginal adverse impact of Covid-19 shock is weaker on banks with higher liquid assets holdings on the onset of the Covid-19 shock. Moreover, larger banks were hit harder during the first quarter of 2020, however, they also recovered more quickly during the second quarter. Results are robust with alternative estimation methods, matched sample of Islamic and conventional banks, cross-sectional analysis with fever period and extended sample period. © 2022 Elsevier B.V.

Biomarkers for Thrombosis in COVID-19: A Role for High Sensitivity Troponin-I and Immature Platelet Fraction?

Biomarkers for Thrombosis in COVID-19: A Role for High Sensitivity Troponin-I and Immature Platelet Fraction? Introduction Coronavirus disease 2019 (COVID-19) is associated with increased risk of thrombosis with both venous and arterial thromboembolism observed. While d-dimer elevation has been shown to be associated with thrombosis, this elevation is present in over 50% of COVID-19 infections demonstrating a clear need for more specific biomarkers of thrombosis in this population. While there are a variety of theories to explain the increased risk for thrombosis: all center on Virchow's triad, specifically hypercoagulability and inflammation. Platelets play a significant role in hypercoagulability. Immature platelets, which are thought to be hyper-reactive, may specifically be associated with thrombosis in COVID-19. It would thus be reasonable to expect immature platelet fraction (IPF) and immature platelet count (IPC) to be predictive biomarkers of thrombosis in this population. Beyond hypercoagulability, High-Sensitivity (HS) Cardiac troponin-I can be a biomarker of inflammation and may also be predictive of thrombotic events in COVID-19. The aim of this study was to evaluate the relationship between IPF, IPC, HS cardiac troponin-I and thrombotic events in COVID-19. Methods Using a single center COVID-19 data registry, we extracted all patients with COVID-19 at our single center between May 1, 2020 and January 1, 2021. Patients were stratified into two groups based on thrombotic events during hospitalization, the thrombosis and no thrombosis groups. Biomarker values, including IPF, IPC, platelet counts, d-dimer, and HS cardiac troponin I were extracted. Two-sided Wilcoxon rank test was conducted to test group differences in IPF, IPC, platelet, d-dimer, and HS cardiac troponin-I values. Results There were no significant differences in measurements of IPF at admission, peak IPF, platelet count at admission, peak platelet count, IPC at admission, and peak IPC between the thrombosis and no thrombosis groups. Minimum platelet count values were significantly lower in the thrombosis group compared to the no thrombosis group. D-dimer and troponin values were significantly higher in the thrombosis group than the no thrombosis group. (Table 1) Discussion To our knowledge this is the first study assessing the relationship between IPF, IPC, HS cardiac troponin-I and thrombosis in COVID-19. HS cardiac troponin did appear to be a predictive biomarker for thrombosis in COVID-19. This may be related to vascular inflammation playing a significant role in thrombosis. It may also be secondary to myocardial inflammation associated with severe disease in COVID-19.3 Patients with more severe disease are more prone to thrombosis. Unsurprisingly, our study corroborates evidence in the literature that d-dimer is associated with thrombotic events in COVID-19. On the other hand, IPF and IPC do not appear to be predictive biomarkers for thrombosis in this cohort. This appears consistent with the limited data assessing the relationship between IPF, IPC, and thrombosis outside of COVID-19. This does not dispel the importance of immature platelets in COVID-19, however. IPF and IPC are increased in patients with COVID-19, and our published data indicates they are predictors of COVID-19 severity. However, the relationship between immature platelets and outcomes in acute illness can be complex, as in sepsis, where the trend of IPC is associated with mortality, rather than the initial value. Future studies should delineate the relationship between trends in IPF or IPC and outcomes in COVID-19. Furthermore, it is crucial to define biomarkers of thrombosis and disease severity and mortality in COVID-19 which can potentially guide therapeutic interventions. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Immature platelets as a biomarker for disease severity and mortality in COVID-19 patients

Background : COVID-19, caused by SARS-CoV-2, is a contagious life-threatening viral disease that has killed more than 2.13M people worldwide. Attempts have been made to identify a biomarker to stratify disease severity to improve resource allocation. Patients with SARS-COV-2 infection manifest with higher inflammatory response and platelet hyperactivity;this raises the question of the role of thrombopoiesis in COVID-19. Immature platelet fraction (IPF%) can be used to assess bone marrow activity, thrombopoiesis. Aims : This study investigates whether the level of thrombopoiesis associates with COVID-19 severity defined by ICU stay, ventilator use, and mortality. Methods : A large cohort of 678 (658, 97% hospitalized) wellcharacterized COVID-19 patients was analyzed. This included 52.4% males, 38.9% White, 26.8% Black, 25.2% Hispanic, 2.5% Asian/AI/ PI, and 6.5% Other. Overall age was 61.5 ± 16.7 years. Other characteristics reviewed included smoking status, comorbidities, and steroid use at the time of admission. Additionally, 5.6% ( n = 38) had thrombosis during admission. Group differences in continuous and categorical variables were tested using Two-sided Wilcoxon rank sum test and Mantel Chi-Square statistics, respectively. Results : Elevated IPF% at presentation was predictive of length of hospitalization ( P < 0.01). Additionally, peak values of IPF% were significantly higher among deceased patients compared to recovered patients (7.9 ± 6.3 vs 5.4 ± 7.8, P < 0.01). Approximately 20% of hospitalized patients were admitted to the intensive care unit (ICU) with an average length of stay 11 ± 12 days;these had significantly higher IPF% at presentation compared to those who did not require ICU care (5.8 ± 4.6 vs 4.7 ± 2.6, P < 0.01). Conclusions : Higher IPF%, as a biomarker of thrombopoiesis, can predict disease severity, length of stay, and mortality risk among hospitalized COVID-19 patients.

Are investors’ attention and uncertainty aversion the risk factors for stock markets? International evidence from the covid-19 crisis

In this paper, we examine the impact of investors’ attention to COVID-19 on stock market returns and the moderating effect of national culture on this relationship. Using daily data from 34 countries over the period 23 January to 12 June 2020, and measuring investors’ attention with the Google search volume (GSV) of the word “coronavirus” for each country, we find that investors’ enhanced attention to the COVID-19 pandemic results in negative stock market returns. Further, measuring the national culture with the uncertainty avoidance index (the aspect of national culture which measures the cross-country differences in decision-making under stress and ambiguity), we find that the negative impact of investors’ attention on stock market returns is stronger in countries where investors possess higher uncertainty avoidance cultural values. Our findings imply that uncertainty avoidance cultural values of investors promote financial market instability amid the crisis. © 2020 by the authors. Li-censee MDPI, Basel, Switzerland.