Evaluation of the active constituents of Nilavembu Kudineer for viral replication inhibition against SARS‐CoV‐2: An approach to targeting RNA‐dependent RNA polymerase (RdRp)

The World Health Organization has declared the novel coronavirus (COVID‐19) outbreak a global pandemic and emerging threat to people in the 21st century. SARS‐CoV‐2 constitutes RNA‐Dependent RNA Polymerase (RdRp) viral proteins, a critical target in the viral replication process. No FDA‐approved drug is currently available, and there is a high demand for therapeutic strategies against COVID‐19. In search of the anti‐COVID‐19 compound from traditional medicine, we evaluated the active moieties from Nilavembu Kudineer (NK), a poly‐herbal Siddha formulation recommended by AYUSH against COVID‐19. We conducted a preliminary docking analysis of 355 phytochemicals (retrieved from PubChem and IMPPAT databases) present in NK against RdRp viral protein (PDB ID: 7B3B) using COVID‐19 Docking Server and further with AutoDockTool‐1.5.6. MD simulation studies confirmed that Orientin (L1), Vitexin (L2), and Kasuagamycin (L3) revealed better binding activity against RdRp (PDB ID: 7B3B) in comparison with Remdesivir. The study suggests a potential scaffold for developing drug candidates against COVID‐19. PRACTICAL APPLICATIONS: Nilavembu Kudineer is a poly‐herbal Siddha formulation effective against various diseases like cough, fever, breathing problems, etc. This study shows that different phytoconstituents identified from Nilavembu Kudineer were subjected to in silico and ADME analyses. Out of the former 355 phytochemical molecules, Orientin (L1), Vitexin (L2), and Kasuagamycin (L3) showed better binding activity against RdRp viral protein (PDB ID: 7B3B) in comparison with the synthetic repurposed drug. Our work explores the search for an anti‐COVID‐19 compound from traditional medicine like Nilavembu Kudineer, which can be a potential scaffold for developing drug candidates against COVID‐19.

Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential.

COVID-19 infection is now considered one of the leading causes of human death. As an attempt towards the discovery of novel medications for the COVID-19 pandemic, nineteen novel compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed and synthesized via a click reaction based on our previous work. The novel compounds were assessed using an in vitro effect on the growth of SARS-CoV-2 virus-infested Vero cells with different compound concentrations: 1 and 10 µM. The data revealed that most of these derivatives showed potent cellular anti-COVID-19 activity and inhibited viral replication by more than 50% with no or weak cytotoxic effect on harboring cells. In addition, in vitro assay employing the SARS-CoV-2-Main protease inhibition assay was done to test the inhibitors' ability to block the common primary protease of the SARS-CoV-2 virus as a mode of action. The obtained results show that the one non-linker analog 6h and two amide-based linkers 6i and 6q were the most active compounds with IC50 values of 5.08, 3.16, and 7.55 µM, respectively, against the viral protease in comparison to data of the selective antiviral agent GC-376. Molecular modeling studies were done for compound placement within the binding pocket of protease which reveal conserved residues hydrogen bonding and non-hydrogen interactions of 6i analog fragments: triazole scaffold, aryl part, and linker. Moreover, the stability of compounds and their interactions with the target pocket were also studied and analyzed by molecular dynamic simulations. The physicochemical and toxicity profiles were predicted, and the results show that compounds behave as an antiviral activity with low or no cellular or organ toxicity. All research results point to the potential usage of new chemotype potent derivatives as promising leads to be explored in vivo that might open the door to rational drug development of SARS-CoV-2 Main protease potent medicines.

Evaluation of the active constituents of Nilavembu Kudineer for viral replication inhibition against SARS-CoV-2: An approach to targeting RNA-dependent RNA polymerase (RdRp).

The World Health Organization has declared the novel coronavirus (COVID-19) outbreak a global pandemic and emerging threat to people in the 21st century. SARS-CoV-2 constitutes RNA-Dependent RNA Polymerase (RdRp) viral proteins, a critical target in the viral replication process. No FDA-approved drug is currently available, and there is a high demand for therapeutic strategies against COVID-19. In search of the anti-COVID-19 compound from traditional medicine, we evaluated the active moieties from Nilavembu Kudineer (NK), a poly-herbal Siddha formulation recommended by AYUSH against COVID-19. We conducted a preliminary docking analysis of 355 phytochemicals (retrieved from PubChem and IMPPAT databases) present in NK against RdRp viral protein (PDB ID: 7B3B) using COVID-19 Docking Server and further with AutoDockTool-1.5.6. MD simulation studies confirmed that Orientin (L1), Vitexin (L2), and Kasuagamycin (L3) revealed better binding activity against RdRp (PDB ID: 7B3B) in comparison with Remdesivir. The study suggests a potential scaffold for developing drug candidates against COVID-19. PRACTICAL APPLICATIONS: Nilavembu Kudineer is a poly-herbal Siddha formulation effective against various diseases like cough, fever, breathing problems, etc. This study shows that different phytoconstituents identified from Nilavembu Kudineer were subjected to in silico and ADME analyses. Out of the former 355 phytochemical molecules, Orientin (L1), Vitexin (L2), and Kasuagamycin (L3) showed better binding activity against RdRp viral protein (PDB ID: 7B3B) in comparison with the synthetic repurposed drug. Our work explores the search for an anti-COVID-19 compound from traditional medicine like Nilavembu Kudineer, which can be a potential scaffold for developing drug candidates against COVID-19.

An Evaluation of Different Types of Peptone as Partial Substitutes for Animal-derived Serum in Vero Cell Culture.

Vero cells are one of the most frequently used cell types in virology. They can be used not only as a vehicle for the replication of viruses, but also as a model for investigating viral infectivity, cytopathology and vaccine production. There is increasing awareness of the need to limit the use of animal-derived components in cell culture media for a number of reasons, which include reducing the risk of contamination and decreasing costs related to the downstream processing of commercial products obtained via cell culture. The current study evaluates the use of protein hydrolysates (PHLs), also known as peptones, as partial substitutes for fetal bovine serum (FBS) in Vero cell culture. Eleven plant-based, two yeast-based, and three casein-based peptones were assessed, with different batches evaluated in the study. We tested the effects of three concentration ratios of FBS and peptone on Vero cell proliferation, four days after the initial cell seeding. Some of the tested peptones, when in combination with a minimal 1% level of FBS, supported cell proliferation rates equivalent to those achieved with 10% FBS. Collectively, our findings showed that plant-based peptones could represent promising options for the successful formulation of serum-reduced cell culture media for vaccine production. This is especially relevant in the context of the current COVID-19 pandemic, in view of the urgent need for SARS-CoV-2 virus production for certain types of vaccine. The current study contributes to the Three Rs principle of reduction, as well as addressing animal ethics concerns associated with FBS, by repurposing PHLs for use in cell culture.

Nanocomposite of gold nanoparticles@nickel disulfide-plant derived carbon for molecularly imprinted electrochemical determination of favipiravir

A molecularly imprinted electrochemical sensor was fabricated for sensitive and selective detection of anti-COVID 19 drug favipiravir (FAV). The sensor is based on the synthesis of biomass-derived carbon (BC) and nickel disulfide nanospheres (NiS2 NS), which were used to decorate glassy carbon electrode (GCE). Then, the gold nanoparticles (AuNPs) were electro- deposited on the surface of NiS2 NS/BC/GCE to enhance conductivity, increase electron transfer, and aid polymerization of p-aminothiophenol (p-ATP) functional monomer. The fabrication steps were characterized using different morphological and electrochemical techniques. Variables affecting the formation of molecularly imprinted layers and the determination of FAV were optimized. Under optimum conditions, the oxidation current (Ipa) was increased upon addition of FAV in the range of 0.42-1100 nM with a limit of detection (LOD, S/N) of 0.13 nM. The as-fabricated sensor possesses several advantages such as high sensitivity and selectivity, good reproducibility, and acceptable stability. Furthermore, the proposed molecularly imprinted –based electrochemical sensor was efficiently applied for the determination of FAV in tablets and human serum samples with recoveries % of 99.2 to 102.1 % and RSDs % in the range of 2.4-3.2 %, which confirms the reliability of the sensor to detect FAV in different matrices.

Imaging of COVID-19 vasculopathy from head to toe: Egyptian collective experience after 2 years of the pandemic

Background COVID-19 vasculopathy is a critical condition that impacts the disease prognosis including vasculitis and thromboembolic complications. This study aimed to provide the Egyptian experience about the COVID-19 vasculopathy during the past two years of the pandemic and to collectively include the different modalities and imaging techniques for the diagnosis of cerebrovascular, pulmonary, gastrointestinal, and peripheral arterial vascular complications. Results This is a multi-center retrospective analysis of 3500 PCR-proved COVID-19 infection between March 2020 and December 2021. A cohort of 282 consecutive patients with COVID-19 vasculopathy was considered for inclusion. They included 204 males and 78 females (72:28%). The mean age was 68 years, and age ranged from 48 to 90 years. Five radiologists evaluated the different imaging examinations in consensus including computed tomography (CT), CT-angiography (CTA), CT-perfusion (CTP), magnetic resonance imaging (MRI), MR-arteriography (MRA), and MR-venography (MRV). 244/282 (86.5%) patients suffered from non-hemorrhagic cerebral ischemic infarctions. 13/282 (4.6%) patients suffered from hemorrhagic cerebral infarctions. 5/282 (1.8%) patients suffered from cerebral vasculitis. Pulmonary vascular angiopathy was detected in 10/282 (3.5%) patients, including pulmonary embolism in 10/10 patients, pulmonary infarctions in 8/10 patients, pulmonary vascular enlargement in 5/10 patients, and vascular "tree-in-bud" sign in 2/10 patients. Intestinal ischemia and small bowel obstruction were detected in 3/282 patients (1%) while GIT bleeding was encountered in 4/282 patients (1.4%). Lower limb arterial ischemia was found in 3/282 patients (1%). Additionally;39/282 (13.8%) patients developed peripheral deep venous thrombosis (DVT) due to prolonged ICU recumbence while 28/282 (10%) patients developed jugular vein thrombosis sequel to prolonged catheterization. A p value (0.002) and (r) = 0.8 statistically proved strong significant relation between COVID-19 vasculopathy and D-dimer levels. Conclusions Multi-system vasculopathy was a serious complication of COVID-19 which impacted the patients' morbidity and mortality. An Egyptian experience about the COVID-19 vasculopathy during the past two years of the pandemic was provided. It encountered the different modalities and imaging techniques for the diagnosis of cerebrovascular, pulmonary, gastrointestinal, and peripheral arterial COVID-19 vascular complications.

EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones.

For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apoptosis, and tumor-cell metastasis, an indispensable objective is to design new scaffolds or drugs that possess combined action or dual effect, such as kinase and COX-2 inhibition. The start compounds A1 to A6 were prepared through the diazo coupling of 3-aminoacetophenone with a corresponding phenol and then condensed with two new chalcone series, C7-18. The newly synthesized compounds were assessed against both COX-2 and epidermal growth factor receptor (EGFR) for their inhibitory effect. All novel compounds were screened for cytotoxicity against five cancer cell lines. Compounds C9 and G10 exhibited potent EGFR inhibition with IC50 values of 0.8 and 1.1 µM, respectively. Additionally, they also displayed great COX-2 inhibition with IC50 values of 1.27 and 1.88 µM, respectively. Furthermore, the target compounds were assessed for their cytotoxicity against pancreatic ductal cancer (Panc-1), lung cancer (H-460), human colon cancer (HT-29), human malignant melanoma (A375) and pancreatic cancer (PaCa-2) cell lines. Interestingly, compounds C10 and G12 exhibited the strongest cytotoxic effect against PaCa-2 with average IC50 values of 0.9 and 0.8 µM, respectively. To understand the possible binding modes of the compounds under investigation with the receptor cites of EGFR and COX-2, a virtual docking study was conducted.

Excess of cesarean births in pregnant women with COVID-19: A meta-analysis.

BACKGROUND: Studies have suggested that cesarean birth in pregnant women with COVID-19 may decrease maternal adverse events and perinatal transmission. This systematic review aimed to evaluate variations in clinical presentation, laboratory findings, and maternal/neonatal outcomes in COVID-19 patients who delivered vaginally versus via cesarean. METHODS: A comprehensive search following PRISMA guidelines was performed for studies published up to May 23, 2020, using PubMed, Web of Science, Scopus, Embase, Cochrane, Science Direct, and clinicaltrials.gov. Original retrospective and prospective studies, case reports, or case series with sufficient data for estimating the association of COVID-19 with different pregnancy outcomes with no language restriction and published in peer-reviewed journals were included. Pooled mean and arcsine transformation proportions were applied. Next, a two-arm meta-analysis was performed comparing the perinatal outcomes between the study groups. RESULTS: Forty-two studies with a total of 602 pregnant women with COVID-19 were included. The mean age was 31.8 years. Subgroup analysis showed that Americans had the lowest gestational age (mean = 32.7, 95%CI = 27.0-38.4, P < 0.001) and the highest incidence of maternal ICU admission (95%CI = 0.45%-2.20, P < 0.001) of all nationalities in the study. There was no significant difference in perinatal complications, premature rupture of membrane, placenta previa/accreta, or gestational hypertension/pre-eclampsia between women who delivered vaginally versus by cesarean. Importantly, there were also no significant differences in maternal or neonatal outcomes. CONCLUSION: Vaginal delivery was not associated with worse maternal or neonatal outcomes when compared with cesarean. The decision to pursue a cesarean birth should be based on standard indications, not COVID-19 status.

Nursing students' and educators' experience with e-learning during a pandemic: An online survey.

BACKGROUND: Nursing students' and educators' experiences with e-learning during the Coronavirus disease 2019 (COVID-19) pandemic are unknown in most countries. AIM: To (1) describe and compare Egyptian nursing students' and educators' experiences with e-learning during the COVID-19 pandemic and (2) elicit participants' preferences for responding to online versus paper questionnaires. METHODS: This is a cross-sectional online survey of nursing students (undergraduate and postgraduate; n =580) and nursing educators (n = 95) in one faculty of nursing in Egypt. The survey assessed participants'characteristics, preferences for online versus paper surveys, and 11 dimensionsrelated to the e-learning experience, such as perceived competency, satisfaction, cognitive presence, and the preferred platforms for e-learning. RESULTS: About 91% of students and 80% of educators received either no or inadequate training on e-learning before the pandemic. Students' and educators' experiences significantly differed (p-value < 0.001) in most of the examined dimensions, with educators having better experiences. About 71% of the students and 76% of the educators preferred responding to online surveys. The Strengths, Weaknesses, Opportunities, and Threats (SWOT analysis) of e-learning were mapped. CONCLUSION: Students are in more need of training on e-learning than educators, and this training is a must before any attempt to undertake online exams. The online survey is a preferred methodology among Egyptian nursing educators and students. The provided SWOT analysis may help administrators best implement and support e-learning during infection outbreaks.

Strawberry and Ginger Silver Nanoparticles as Potential Inhibitors for SARS-CoV-2 Assisted by In Silico Modeling and Metabolic Profiling.

SARS-CoV-2 (COVID-19), a novel coronavirus causing life-threatening pneumonia, caused a pandemic starting in 2019 and caused unprecedented economic and health crises all over the globe. This requires the rapid discovery of anti-SARS-CoV-2 drug candidates to overcome this life-threatening pandemic. Strawberry (Fragaria ananassa Duch.) and ginger (Zingiber officinale) methanolic extracts were used for silver nanoparticle (AgNPs) synthesis to explore their SARS-CoV-2 inhibitory potential. Moreover, an in silico study was performed to explore the possible chemical compounds that might be responsible for the anti-SARS-CoV-2 potential. The characterization of the green synthesized AgNPs was carried out with transmission electron microscope (TEM), Fourier-transform infrared, spectroscopy ultraviolet-visible spectroscopy, zeta potential, and a dynamic light-scattering technique. The metabolic profiling of strawberry and ginger methanolic extract was assessed using liquid chromatography coupled with high-resolution mass spectrometry. The antiviral potential against SARS-CoV-2 was evaluated using an MTT assay. Moreover, in silico modeling and the molecular dynamic study were conducted via AutoDock Vina to demonstrate the potential of the dereplicated compounds to bind to some of the SARS-CoV-2 proteins. The TEM analysis of strawberry and ginger AgNPs showed spherical nanoparticles with mean sizes of 5.89 nm and 5.77 nm for strawberry and ginger, respectively. The UV-Visible spectrophotometric analysis showed an absorption peak at λmax of 400 nm for strawberry AgNPs and 405 nm for ginger AgNPs. The Zeta potential values of the AgNPs of the methanolic extract of strawberry was -39.4 mV, while for AgNPs of ginger methanolic extract it was -42.6 mV, which indicates a high stability of the biosynthesized nanoparticles. The strawberry methanolic extract and the green synthesized AgNPs of ginger showed the highest antiviral activity against SARS-CoV-2. Dereplication of the secondary metabolites from the crude methanolic extracts of strawberry and ginger resulted in the annotation of different classes of compounds including phenolic, flavonoids, fatty acids, sesquiterpenes, triterpenes, sterols, and others. The docking study was able to predict the different patterns of interaction between the different compounds of strawberry and ginger with seven SARS-CoV-2 protein targets including five viral proteins (Mpro, ADP ribose phosphatase, NSP14, NSP16, PLpro) and two humans (AAK1, Cathepsin L). The molecular docking and dynamics simulation study showed that neohesperidin demonstrated the potential to bind to both human AAK1 protein and SARS-CoV-2 NSP16 protein, which makes this compound of special interest as a potential dual inhibitor. Overall, the present study provides promise for Anti-SARS-CoV-2 green synthesized AgNPs, which could be developed in the future into a new anti-SARS-CoV-2 drug.

African Americans Struggle With the Current COVID-19.

OBJECTIVES: Our study aims to explore the differential impact of this pandemic on clinical presentations and outcomes in African Americans (AAs) compared to white patients. BACKGROUND: AAs have worse outcomes compared to whites while facing heart diseases, stroke, cancer, asthma, influenza and pneumonia, diabetes, and HIV/AIDS. However, there is no current study to show the impact of COVID-19 pandemic on the AA communities. METHODS: This is a retrospective study that included patients with laboratory-confirmed COVID-19 from 2 tertiary centers in New Orleans, LA. Clinical and laboratory data were collected. Multivariate analyses were performed to identify the risk factors associated with adverse events. RESULTS: A total of 157 patients were identified. Of these, 134 (77%) were AAs, whereas 23.4% of patients were Whites. Interestingly, AA were younger, with a mean age of 63 ± 13.4 compared to 75.7 ± 23 years in Whites (P < 0.001). Thirty-seven patients presented with no insurance, and 34 of them were AA. SOFA Score was significantly higher in AA (2.57 ± 2.1) compared to White patients (1.69 ± 1.7), P = 0.041. Elevated SOFA score was associated with higher odds for intubation (odds ratio = 1.6, 95% confidence interval = 1.32-1.93, P < 0.001). AA had more prolonged length of hospital stays (11.1 ± 13.4 days vs 7.7 ± 23 days) than in Whites, P = 0.01. CONCLUSION: AAs present with more advanced disease and eventually have worse outcomes from COVID-19 infection. Future studies are warranted for further investigations that should impact the need for providing additional resources to the AA communities.