Identification of natural antiviral drug candidates against Tilapia Lake Virus: Computational drug design approaches.

Tilapia Lake Virus (TiLV) is a disease that affects tilapia fish, causing a high rate of sudden death at any stage in their life cycle. Unfortunately, there are currently no effective antiviral drugs or vaccines to prevent or control the progression of this disease. Researchers have discovered that the CRM1 protein plays a critical function in the development and spreading of animal viruses. By inhibiting CRM1, the virus's spread in commercial fish farms can be suppressed. With this in mind, this study intended to identify potential antiviral drugs from two different tropical mangrove plants from tropical regions: Heritiera fomes and Ceriops candolleana. To identify promising compounds that target the CRM1 protein, a computer-aided drug discovery approach is employed containing molecular docking, ADME (absorption, distribution, metabolism and excretion) analysis, toxicity assessment as well as molecular dynamics (MD) simulation. To estimate binding affinities of all phytochemicals, molecular docking is used and the top three candidate compounds with the highest docking scores were selected, which are CID107876 (-8.3 Kcal/mol), CID12795736 (-8.2 Kcal/mol), and CID12303662 (-7.9 Kcal/mol). We also evaluated the ADME and toxicity properties of these compounds. Finally, MD simulation was conducted to analyze the stability of the protein-ligand complex structures and confirm the suitability of these compounds. The computational study demonstrated that the phytochemicals found in H. fomes and C. candolleana could potentially serve as important inhibitors of TiLV, offering practical utility. However, further in vivo investigations are necessary to investigate and potentially confirm the effectiveness of these compounds as antiviral drugs against the virus TiLV.

Multi-omics prognostic signatures of IPO11 mRNA expression and clinical outcomes in colorectal cancer using bioinformatics approaches.

The most prevalent malignant illness of the gastrointestinal system, colorectal cancer, is the third most prevalent cancer in males and the second most prevalent cancer in women. Importin-11 is a protein that acts as a regulator of cancer cell proliferation in colorectal tumours by conveying ß-catenin to the cell nucleus. However, the IPO11 gene was found to encode a protein called Importin-11, which functions as a nucleus importer for the cell. As a result, preventing ß-catenin from entering the nucleus requires blocking Importin-11. As a result, we conducted a multi-omics investigation to assess IPO11 gene potential as a therapeutic biomarker for human colorectal cancer (CC). Oncomine, GEPIA2, immunohisto-chemistry, and UALCAN databases were used to analyses the mRNA expression profiles of IPO11 in CC. The investigation has yielded clear evidence of the increase of IPO11 expression in CC subtypes, as indicated by the data acquired. Analysing CC research from the cBioPortal database, the study discovered three new missense mutations in the importin-11 protein sequence at a frequency of 0.00-1.50% copy number changes. Additionally, the Kaplan-Meier plots demonstrated a strong connection concerning IPO11 downregulation and a poorer CC patient survival rate. The co-expressed gene profile of IPO11 was likewise associated with the onset of CC. IPO11 co-expressed gene profile was also linked to CC development. Moreover, the correlation analysis using bc-GenExMiner and the UCSC Xena server identified KIF2A as the most positively co-expressed gene. The study found that KIF2A and its co-expressed genes were involved in a wide variety of cancer progression pathways using the Enrichr database. Cumulatively, this result will not only provide new information about the expression of IPO11 associated with CC progression and patient survival, but could also serve as a therapeutic biomarker for treating CC in a significant and worthwhile manner. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00259-2.

The use of marine sponge species as a bioindicator to monitor metal pollution in Red Sea, Saudi Arabia.

The existing data on trace elements of benthic sea organisms is scarce. Yet, the pressing issue of environmental contamination has spurred a surge in the use of organisms as biomonitors. In this study, sediment cores were sampled with the sponges, and metal concentrations were determined in both samples using ICP-MS. The mean concentrations of metals in benthic sediments and sponge species analyzed in this study differed significantly (Sediment > Phorbas species > Negombata magnifica > Callyspongia species > Amphimedon chloros). This could be due to the varying capacity of each sponge species to accumulate a particular metal by different means. Negombata magnifica and Phorbas species appear to be indicators, accumulators, or hyper-accumulators of Cu and Mn, while Callyspongia species is an indicator, accumulator, or hyper-accumulator of Cu only due to bioconcentration factor > 1 for the aforementioned metals. Concentrations of Cu and As in sediment were below the Effects Range Median but above the Effects Range Low threshold, hence the need to give more attention to these metals. This research provides a baseline dataset for designing monitoring strategies on this ecosystem and using sponge species for biomonitoring.

Marine-derived sea urchin compounds as potential anti-cancer drug candidate against colorectal cancer: In silico and in vitro studies.

Sea urchin-derived compounds are potential candidates for the development of effective drugs for the treatment of cancer diseases. In this study, 19 compounds derived from sea urchin (Diadema savignyi) were used to treat colorectal cancer using the HCT116 cell line. However, molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamic (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) were used to confirm the ligand-protein interaction. Interactions of Importin-11 receptor with sea urchin compounds reveal that four compounds have higher binding affinities (ranging from -8.6 to -7.1 kcal/mol). In vitro testing revealed that the CID 6432458 compound was effective (docking score of -8.6 kcal/mol) against the HCT116 cell line. The cytotoxicity of HCT116 has been documented, with an IC50 value of 6.885 ± 4. MTT assay, apoptosis analysis, and cell cycle assay were utilized to examine cell death in colorectal cancer. In the MTT experiment, 15 µM and 20 µM dosages were associated with 77% cell death; however, flow cytometry analysis using the IC50 value revealed that the selected chemical induced greater apoptosis in the HCT116 cell line (58.5%). The gene expression data revealed that the apoptotic gene BAX is expressed at a higher level than the BCL-2 gene. The IPO11 gene was downregulated during treatment. In the experiment involving the cell cycle, the S phase for the 30  µM dose showed 75.1% apoptosis, which was greater than the other concentrations used alone. These in silico and in vitro analysis will not only provide new information about Importin-11 receptor and insight into colorectal cancer but will also facilitate the development of natural compounds in a significant and worthwhile manner.

Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1.

Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of -10.4, -10.1, and -9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.

Elemental Composition of Above and Belowground Mangrove Tissue and Sediment in Managed and Unmanaged Compartments of the Matang Mangrove Forest Reserve.

Mangrove productivity depends on the storage of nutrients and elements. Elemental concentrations were examined in leaves, roots, and sediments for three age stands (15, 25 years, and VJR) of Rhizophora apiculata in the Matang Mangrove Forest Reserve (MMFR). Six compartments with two compartments each for each age group were used to analyze sixteen elements. Four types of elemental patterns were examined with decreasing order during analysis: (1) Cd < Cu < Pb < Zn < Mg < Mn < Fe < K < Na < Ca and P% < S% < N% < C% in leaves, (2) Cd < Pb < Cu < Zn < Mg < Mn < Fe < K < Na < Ca and P% < S% < N% < C% in roots, (3) Cd < Pb < Cu < Zn < Mg < Mn < K < Fe < Na < Ca and P% < N% < S% < C% in sediment samples and (4) Cd(S) < Pb(S) < Cu(S) < Zn(S) < Mg(S) < Mn(L) < K(L) < Fe(S) < Na(R) < Ca(R) and P%(S) < S%(S) < N%(L) < C%(R) collectively for all samples. Evidence that elements do not store primarily in above-ground biomass can be found in the observation that elements are stored more in sediment and roots. The outcome of the present study shows that the rate of increase of elements in trees (leaves and roots) was less as compared to sediments, where the elemental concentration increased considerably with time. Elemental concentration comparison within three age classes showed that C, N, and S were significantly different in all three types of samples. The δ15N ratios showed positive values in all six compartments which supported the concept that the δ15N ratio could not be observed in N concentration in this study. The δ13C values showed more negative values in all six compartments which represented less salinity and a freshwater intake. The S, P, and heavy metals concentrations were high. The concentrations of Cd, P, N, C, and S in the sediment influenced variations in four compartments in accordance with the three mangrove age groups. The results of this study can be utilized to create management plans for MMFR and conduct risk assessments of the elements' concentration in sediment.

Population dynamics and fecundity estimates of Long-spined Black Sea Urchin Diadema savignyi (Audouin, 1890) from the Red Sea, Saudi Arabia.

Sea Urchin is not only the crucial keystone species for the coral reef restoration but also it has antimicrobial and anti-cancer activities. This study undertaken to focus on length weight relationship, size fecundity distribution and the estimation of fecundity from the long-spined Sea Urchin, Diadema savignyi at the coastal water of the middle Red Sea, Saudi Arabia. A total of 633 specimen of D. savignyi has been collected from the coastal water of Obhur Creak during the sampling time. In each species, total length (TL) measured as a TW = 11.908 × 0.9995 (R2 = 0.8975) through the linear regression graph and digital slide callipers and, individual body weight estimated by the digital balance. The natural and fishing mortality 2.02/yr and 0.19/yr respectively has documented from study area. The Asymptotic length value (L∞) (cm) were estimated 7.35 where the growth coefficient (K) was 0.67 from the monthly length-frequency numeric data by using FAO FISAT II software for generating and estimating the population parameters and age. However, the recruitment pattern was observed to be increased gradually with the maximum recruitment peak between the months of September and October 2021. Therefore, the estimation of fecundity varied from 49,226 ova (total length 3.1 cm) to 466,133 ova (total length 6.8). As a result, analysis of the relationship between the absolute fecundity (F) and total length (TL), and between the fecundity and drained body weight (DW), revealed a linear regression model with a positive and significant relationship at p < 0.05. This is the first approach to study the detailed population dynamic of the ecologically and economically important tropical long spine sea urchin (D. savignyi) endemic to the region. However, the result so far obtained from this research would greatly be useful towards the understanding of the detailed population structure and growth patterns that will undoubtedly help us to develop captive breeding, seed production, culture protocols, conservation strategies and isolation bioactive compounds of this high-valued species incommensurate with national and international perspectives.

Rare Earth Elements and Bioavailability in Northern and Southern Central Red Sea Mangroves, Saudi Arabia.

Different hypotheses have been tested about the fractionation and bioavailability of rare earth elements (REE) in mangrove ecosystems. Rare earth elements and bioavailability in the mangrove ecosystem have been of significant concern and are recognized globally as emerging pollutants. Bioavailability and fractionation of rare earth elements were assessed in Jazan and AlWajah mangrove ecosystems. Comparisons between rare earth elements, multi-elemental ratios, geo-accumulation index (Igeo), and bio-concentration factor (BCF) for the two mangroves and the influence of sediment grain size types on concentrations of rare earth elements were carried out. A substantial difference in mean concentrations (mg/kg) of REE (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) was established, except for mean concentrations of Eu, Gd, Tb, Tm, and Lu. In addition, concentrations of REEs were higher in the Jazan mangrove ecosystem. However, REE composition in the two mangroves was dominated by the lighter REE (LREE and MREE), and formed the major contribution to the total sum of REE at 10.2-78.4%, which was greater than the HREE contribution of 11.3-12.9%. The Post Archean Australian Shale (PAAS) normalized values revealed that lighter REE (LREE and MREE) were steadily enriched above heavy REE. More so, low and negative values of R(H/M) were recorded in the Al Wajah mangrove, indicating higher HREE depletion there. The values of BCF for REEs were less than 1 for all the REEs determined; the recorded BCF for Lu (0.33) and Tm (0.32) were the highest, while the lowest BCF recorded was for Nd (0.09). There is a need for periodic monitoring of REE concentrations in the mangroves to keep track of the sources of this metal contamination and develop conservation and control strategies for these important ecosystems.

The efficiency of trace element uptake by seagrass Cymodocea serrulata in Rabigh lagoon, Red Sea.

The search for solutions to environmental pollution has been on the increase, with many questions recently as to which marine organisms can bioaccumulate trace elements in the marine ecosystem. Cadmium, Cr, Cu, Fe, Mn, Ni, Pb, and Zn concentrations in sediment, seawater, and seagrass compartments (root, rhizome, and leaf blade) were determined at Rabigh lagoon, Red Sea. This is to provide an insight into the potential of Cymodocea serrulata to bioaccumulate trace elements and as a good candidate to biomonitor these elements in a natural aquatic ecosystem. Results revealed significant variations in trace element concentrations across the three compartments of C. serrulata and the sites, with site S8 located in the most closed part of the lagoon recording the highest concentrations for all the trace elements. The translocation factor (TFrhizome/root = 1.00) of trace elements was higher in the root compartment. This implies that the root compartment is a better bioindicator of trace elements and has more potential to be utilized for biomonitoring. A significant positive correlation (p < 0.01) was established between the trace element concentrations in sediment, seawater, and the three compartments of C. serrulata except for Mn concentration in the compartments. The seagrass C. serrulata can be used for biomonitoring of trace elements in marine ecosystems as our results provide information on its capacity to bioaccumulate these elements. This is one of the key characteristics of a typical bioindicator of aquatic pollutants.

Nutrient and physicochemical properties as potential causes of stress in mangroves of the central Red Sea.

Mangrove ecosystems are some of the most productive and important sinks for sediment globally. Recently, there has been an increasing interest in possible causes of stress in mangroves, such as nutrient limitation, high salinity, solar radiation and temperature. We measured different factors casing stress and determined how they influenced oxidative stress and growth biomarkers in six study sites dominated by mangroves; Al Lith, South Jeddah, Dahban, Thuwal, Rabigh and Mastorah. Significant differences (P < 0.05) were recorded in water salinities and temperatures, nitrogen and phosphorus content in sediments, and antioxidant enzyme activities in different study sites. The highest salinity (40.75 ‰) and temperature (29.32°C) were recorded in the Rabigh mangrove stand, which corresponds to the lowest dissolved oxygen (5.21 mg/L). Total organic carbon, total nitrogen and total phosphorus in sediment across the study areas were in the order Rabigh>Thuwal>Dahban>Al Lith>South Jeddah>Mastorah. Total nitrogen in mangrove leaves at Rabigh was the highest and about 1.3 times higher than the total nitrogen in South Jeddah mangrove ecosystem, very different from the ratio of total nitrogen in the sediments at Rabigh and South Jeddah mangrove ecosystems. The average values of δ13C (-17.60‰) and δ15N (2.84‰) in the six mangrove ecosystems, and the highest δ13C (-13.62‰) and δ15N (4.39‰) at Rabigh in the sediments suggest that nutrient input differed among study sites. Higher nutrient levels at Rabigh mangrove ecosystem were attributed to restricted circulation, camel grazing and land runoff with agricultural waste during seasonal flooding events. However, N limitation and possibly salinity contributed to stress in Al Lith, South Jeddah, Dahban, Thuwal, Rabigh, and Mastorah mangrove ecosystems. Salinity (r = 0.9012) contribute more to stress at Rabigh.

Fractionation and Distribution of Rare Earth Elements in Marine Sediment and Bioavailability in Avicennia marina in Central Red Sea Mangrove Ecosystems.

Rare earth element fractionation and distribution in the coastal ecosystem have been of significant concern and are recognized worldwide as emerging micro-pollutants. However, unlike other metals such as trace elements, little is known about their uptake by aquatic plants such as the mangrove Avicennia marina, especially in the central Red Sea. We investigated the fractionation of rare earth elements in six mangrove ecosystems in the central Red Sea and bioavailability in mangrove A. marina. The concentrations of rare earth elements, sediment grain sizes, multi-elemental ratios, geo-accumulation index (Igeo) and bioconcentration factor (BCF) vary significantly (p < 0.05) across the six mangrove ecosystems. Higher concentrations of rare earth elements were recorded at Al Lith (LT) (101.53 mg/kg) and South Jeddah (SJ) (73.38 mg/kg) mangrove ecosystems. However, multi-elemental ratio R(M/L) reveals positive values. In contrast, multi-elemental ratio R(H/M) reveals negative values corresponding to fractionation patterns enriched with medium rare earth elements and heavy rare earth elements depletion across the six mangrove ecosystems. BCF values for rare earth elements were <1, but Lutetium (0.32) had the highest BCF among the rare earth elements, suggesting an efficient accumulation of Lutetium than any other rare earth elements. The scale of Igeo revealed strong contamination (4 ≤ Igeo ≥ 5) of sediment with Lanthanum, Cerium, Praseodynium, Samarium, Godolinium, Holmium, Erbium, Ytterbium, and moderate contamination with Thulium, Terbium, and Dysprosium (1 ≤ Igeo ≤ 3). Principal component analysis showed that clay silt sediment grain size influences rare earth element concentrations in the central Red Sea. Our results provide new evidence for rare earth element fractionation and accumulation in sediment and the potential use of mangrove A. marina for rare earth element monitoring in mangrove ecosystems in the central Red Sea.

Compounds Identified from Marine Mangrove Plant (Avicennia alba) as Potential Antiviral Drug Candidates Against WDSV, an In-Silico Approach.

Walleye dermal sarcoma virus (WDSV) is a type of retrovirus, which affects most of the adult walleye fishes during the spawning time. The virus causes multiple epithelial tumors on the fish's skin and fins that are liable for more than 50% of the mortality rate of fish around the world. Till now, no effective antiviral drug or vaccine candidates have been developed that can block the progression of the disease caused by the pathogen. It was found that the 582-amino-acid (aa) residues long internal structural gag polyprotein of the virus plays an important role in virus budding and virion maturation outside of the cell. Inhibition of the protein can block the budding and virion maturation process and can be developed as an antiviral drug candidate against the virus. Therefore, the study aimed to identify potential natural antiviral drug candidates from the tropical mangrove marine plant Avicennia alba, which will be able to block the budding and virion maturation process by inhibiting the activity of the gag protein of the virus. Initially, a homology modeling approach was applied to identify the 3D structure, followed by refinement and validation of the protein. The refined protein structures were then utilized for molecular docking simulation. Eleven phytochemical compounds have been isolated from the marine plant and docked against the virus gag polyprotein. Three compounds, namely Friedlein (CID244297), Phytosterols (CID12303662), and 1-Triacontanol (CID68972) have been selected based on their docking score -8.5 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol, respectively, and were evaluated through ADME (Absorption, Distribution, Metabolism and Excretion), and toxicity properties. Finally, molecular dynamics (MD) simulation was applied to confirm the binding stability of the protein-ligands complex structure. The ADME and toxicity analysis reveal the efficacy and non-toxic properties of the compounds, where MD simulation confirmed the binding stability of the selected three compounds with the targeted protein. This computational study revealed the virtuous value of the selected three compounds against the targeted gag polyprotein and will be effective and promising antiviral candidates against the pathogen in a significant and worthwhile manner. Although in vitro and in vivo study is required for further evaluation of the compounds against the targeted protein.

Impact of novel coronavirus disease (COVID-19) lockdown on ambient air quality of Saudi Arabia.

The outbreak of COVID-19 has spread globally affecting human activities but with improvement in ambient air quality. The first case of the virus in the Kingdom of Saudi Arabia was on the 2nd of March 2020. The impact of COVID-19 lockdown on the ambient air quality of the Kingdom of Saudi Arabia for the first time using data from nine cities was determined in this study. Hourly air quality data, based on concentrations of carbon monoxide (CO), particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3), and meteorological conditions (atmospheric temperature, relative humidity, and wind speed) of the nine cities studied were obtained from Saudi Arabian General Authority of Meteorology and Environmental Protection (GAMEP), for the period between January 2019 to May 2020. Significant variation (p < 0.05) was recorded for the five atmospheric pollutants across the cities before and during the lockdown, with lower concentrations during the lockdown except for the concentration of O3 in Tabuk, Al Qasim, and Haql. This can be a result of NO and O3 reaction, causing the inability of effective O3 depletion. The percentage changes in concentrations of CO (33.60%) and SO2 (44.16%) were higher in Jeddah; PM10 (91.12%) in Riyadh, while NO2 (44.35%) and O3 (18.98%) were highest in Makkah. However, even though there was a decrease in pollutants concentrations during the lockdown, the concentrations for CO, PM10, SO2, NO2, and O3 were still above WHO 24 h and annual mean limit levels. The COVID-19 lockdown in the Kingdom of Saudi Arabia revealed the possibility of significant atmospheric pollutant reduction by controlling traffic, activities by industries, and environmentally friendly transportation programs such as green commuting programs.