Blue biotechnology: Computational screening of sarcophyton cembranoid diterpenes for SARS-CoV-2 main protease inhibition

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding \u3c -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2

Prefrontal tDCS Decreases Pain in Patients with Multiple Sclerosis

Background: In the last few years, transcranial direct current stimulation (tDCS) has emerged as an appealing therapeutic option to improve brain functions. Promising data support the role of prefrontal tDCS in augmenting cognitive performance and ameliorating several neuropsychiatric symptoms, namely pain, fatigue, mood disturbances, and attentional impairment. Such symptoms are commonly encountered in patients with multiple sclerosis (MS). Objective: The main objective of the current work was to evaluate the tDCS effects over the left dorsolateral prefrontal cortex (DLPFC) on pain in MS patients.Our secondary outcomes were to study its influence on attention, fatigue, and mood. Materials and Methods: Sixteen MS patients with chronic neuropathic pain were enrolled in a randomized, sham-controlled, and cross over study Patients randomly received two anodal tDCS blocks (active or sham), each consisting of three consecutive daily tDCS sessions, and held apart by 3 weeks. Evaluations took place before and after each block. To evaluate pain, we used the Brief Pain Inventory (BPI) and the Visual Analog Scale (VAS). Attention was assessed using neurophysiological parameters and the Attention Network Test (ANT). Changes in mood and fatigue were measured using various scales. Results: Compared to sham, active tDCS yielded significant analgesic effects according to VAS and BPI global scales.There were no effects of any block on mood, fatigue, or attention. Conclusion: Based on our results, anodal tDCS over the left DLPFC appears to act in a selective manner and would ameliorate specific symptoms, particularly neuropathic pain. Analgesia might have occurred through the modulation of the emotional pain network. Attention, mood, and fatigue were not improved in this work. This could be partly attributed to the short protocol duration, the small sample size, and the heterogeneity of our MS cohort. Future large-scale studies can benefit from comparing the tDCS effects over different cortical sites, changing the stimulation montage, prolonging the duration of protocol, and coupling tDCS with neuroimaging techniques for a better understanding of its possible mechanism of action

Chemical Profiling of Significant Antioxidant and Phytotoxic Microwave-Extracted Essential Oil from Araucaria heterophylla Resin

Due to the various hazards of using synthetic chemical compounds in pharmaceutics, agriculture, and industry, scientists and researchers do their best to explore and assess new green natural compounds from natural resources with potent activity. The essential oil (EO) from the resin collected from Araucaria heterophylla Salisb. was extracted by the microwave technique and chemically characterized via GC-MS analysis. Furthermore, the extract EO was assessed for its antioxidant and phytotoxic activities. The EO has 33 compounds, mainly terpenes (98.23%), and the major compounds were α-pinene (62.57%), β-pinene (6.60%), germacrene D (5.88%), and β-caryophyllene (3.56%). The extracted EO showed substantial antioxidant activity, where it showed IC50 values of 142.42 and 118.03 mg L−1 for DPPH and ABTS, respectively. On the other hand, the EO revealed considerable phytotoxicity against the weed Chenopodium murale, where the EO showed IC50 values of 304.0, 230.1, and 147.1 mg L−1, for seed germination, seedling shoot growth, and seedling root growth, respectively. Moreover, the EO showed the same pattern of allelopathic inhibition against the weed Sonchus oleraceus, where it showed IC50 values of 295.7, 224.5, and 106.1 mg L−1, for seed germination, seedling shoot growth, and seedling root growth, respectively. The present study showed that the extraction technique affects the constituents of the EO, particularly the quantitative composition. The EO of A. heterophylla resin also revealed considerable antioxidant and phytotoxic activity against weeds. Therefore, it can be considered a promising natural resource that could be integrated into the weed management approach. However, further study is recommended for deep characterization of their authentic compounds and evaluation of their mode of action(s) on a wide spectrum of weeds

In vitro anti-inflammatory and acetylcholinesterase inhibition efficiency of plant extracts from Sinai-Egypt

635-641Ten plant extracts were prepared and tested in in vitro assays against COX-2, COX-1 and acetylcholinesterase with evaluation of their antioxidant properties. The tested extracts exhibited varied anti COX-2 effect and they were superior to celecoxibe (inhibition percentage was 42.67% at 50 µg/mL), reference drug. Lavandula coronopifolia and Scrophularia Libanotica extracts were the efficient inhibitors (100% and 91% at 50 µg/mL respectively). Launaeaspinosa and Pulicaria undulata were the powerful AChE inhibitor (IC50 values were 16.69 and 29.06 µg/mL, respectively) followed with L. coronopifolia and S.libanotica extracts (IC50 values were 61.89 and 49.83 µg/mL, respectively) and they were efficient in scavenging superoxide radicals and metal ions, nitric oxide formation inhibition, as well as, lipid peroxide production suppression. L. coronopifolia and S. Libanotica extracts can be introduced as natural cyclooxygenase-2 inhibitors without affecting cyclooxygenase-1 whereas L. spinosa and P. undulata extracts were potent suppressor for AChE with robust antioxidant properties which suggest the possibility of using the four extracts, L. coronopifolia, S. libanotica, L. spinosa and P. undulata as natural agent in treating neurodegenerative disorder

In vitro anti-inflammatory and acetylcholinesterase inhibition efficiency of plant extracts from Sinai-Egypt

Ten plant extracts were prepared and tested in in vitro assays against COX-2, COX-1 and acetylcholinesterase with evaluation of their antioxidant properties. The tested extracts exhibited varied anti COX-2 effect and they were superior to celecoxibe (inhibition percentage was 42.67% at 50 µg/mL), reference drug. Lavandula coronopifolia and Scrophularia Libanotica extracts were the efficient inhibitors (100% and 91% at 50 µg/mL respectively). Launaeaspinosa and Pulicaria undulata were the powerful AChE inhibitor (IC50 values were 16.69 and 29.06 µg/mL, respectively) followed with L. coronopifolia and S.libanotica extracts (IC50 values were 61.89 and 49.83 µg/mL, respectively) and they were efficient in scavenging superoxide radicals and metal ions, nitric oxide formation inhibition, as well as, lipid peroxide production suppression. L. coronopifolia and S. Libanotica extracts can be introduced as natural cyclooxygenase-2 inhibitors without affecting cyclooxygenase-1 whereas L. spinosa and P. undulata extracts were potent suppressor for AChE with robust antioxidant properties which suggest the possibility of using the four extracts, L. coronopifolia, S. libanotica, L. spinosa and P. undulata as natural agent in treating neurodegenerative disorder

Bioactive Hydroperoxyl Cembranoids from the Red Sea Soft Coral Sarcophyton glaucum

A chemical investigation of an ethyl acetate extract of the Red Sea soft coral Sarcophyton glaucum has led to the isolation of two peroxide diterpenes, 11(S) hydroperoxylsarcoph-12(20)-ene (1), and 12(S)-hydroperoxylsarcoph-10-ene (2), as well as 8-epi-sarcophinone (3). In addition to these three new compounds, two known structures were identified including: ent-sarcophine (4) and sarcophine (5). Structures were elucidated by spectroscopic analysis, with the relative configuration of 1 and 2 confirmed by X-ray diffraction. Isolated compounds were found to be inhibitors of cytochrome P450 1A activity as well as inducers of glutathione S-transferases (GST), quinone reductase (QR), and epoxide hydrolase (mEH) establishing chemo-preventive and tumor anti-initiating activity for these characterized metabolites

Triple malignancy in a single patient including a cervical carcinoma, a basal cell carcinoma of the skin and a neuroendocrine carcinoma from an unknown primary site: A case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>The occurrence of multiple primary cancers is rare. Only a few cases and patient reviews of an association of triple malignancy have been reported.</p> <p>Case presentation</p> <p>We report here a case of a 78-year-old Moroccan woman presenting initially with a synchronous double malignancy, the first in her cervix and the second in her skin. Our patient was treated with radiation therapy for both tumors and remained in good control for 17 years, when she developed a metastatic disease from a neuroendocrine carcinoma of an unknown primary site.</p> <p>Conclusions</p> <p>Although the association of multiple primary cancers can be considered a rare occurrence, improving survival in cancer patients has made this situation more frequent.</p

Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary health care in Qatar.

AIMS/INTRODUCTION:This study determined the prevalence and risk factors for DPN and pDPN in patients with type 2 diabetes (T2D) in primary health care (PHC) and secondary health care (SHC) in Qatar. MATERIALS AND METHODS:This is a cross-sectional multi-center study. Adults with T2D were randomly enrolled from four PHC centres and two Diabetes Centres in SHC in Qatar. Subjects underwent assessment of clinical and metabolic parameters, DPN and pDPN. RESULTS:1,386 subjects with T2D (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P=0.001) and pDPN (18.1% vs 37.5%, P<0.0001) was significantly lower in PHC compared to SHC, whilst those with DPN at high risk for DFU (31.8% vs 40.0%, P=0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P=0.66) was comparably high but undiagnosed pDPN (24.1% vs 71.5%, P<0.0001) was lower in PHC compared to SHC. The odds of DPN and pDPN increased with age and diabetes duration and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whilst pDPN increased with obesity and reduced physical activity. CONCLUSIONS:The prevalence of DPN and pDPN in T2D is lower in PHC compared to SHC and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, ~80% of patients had not been previously diagnosed with DPN in PHC and SHC. Further, we identify a number of modifiable risk factors for PDN and pDPN