Pharmaceutically Active Compounds in Water Bodies—Occurrence, Fate, and Toxicity

The presence of pharmaceutically active compounds (PhACs) in water bodies has been considered an issue of global concern due to their high consumption and release into the environment, especially under pandemic conditions such as current COVID-19 situations. Additionally, the appearance of antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs) threatens the effectiveness of the pharmaceuticals developed to treat certain diseases. To address this problem, there have been efforts to develop efficient and cost-effective (waste)water treatment methods or to upgrade the existing facilities to regenerate clean water resources. According to the reports available in the literature, the effectiveness of these methods is highly dependent on the applied technology and the type and concentration of the PhACs. The efficiency of these systems can also determine the environmental and ecotoxicological effects expected from the release of these compounds. This chapter aims to summarize and discuss the available literature on the occurrence, environmental concentrations, fate, and possible effects of typical PhACs when introduced into receiving environments. The existing research gaps have also been discussed, and recommendations have been provided for further studies. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Antiviral activity of Humulus lupulus (HOP) aqueous extract against MERS-CoV and SARS-CoV-2: in-vitro and in-silico study

Coronaviruses emerged three times in the last two decades and became a source of concern globally. Humulus lupulus plant has been used widely in medical science. Our objective in this study was to determine the effects of the crude extract of H. lupulus in inhibiting MERS-CoV and SARS-CoV-2 viruses' replication in vitro using Vero E6 cell lines and predict the antiviral activity of its identified compounds against the receptor binding (RBD) protein of both viruses in silico. We determined the concentration of the extract that induced less than 50% cell toxicity (CC50), and the antiviral activity based on IC50 and plaque reduction assay. We used molecular docking simulation to predict the potential of known active compounds in H. lupulus to inhibit the RBD protein. H. lupulus extract showed very low toxicity on Vero E6 cells with CC50= 23.25 µg/µL and antiviral activity toward MERS-CoV and SARS-CoV-2 with IC50= 0.18 and 0.9 µg/µL, respectively. The crude extract showed inhibition rate of 84.6% with MERS-CoV and 80% with SARS-CoV-2. In silico analysis predicted the compounds 5′-prenylxanthohumo, xanthogalenol, dehydrocycloxanthohumol hydrate, 6-prenylnaringenin, isoxanthohumol, catechin gallate, epicatechin gallate, 8-prenylnaringenin and xanthohumol to inhibit MERS-CoV and SARS-CoV-2 invasion of host cells by interfering with viral spike protein and the host cell receptor recognition process. Drug likeness and toxicity risk prediction analysis confirmed their capability as potential drugs. Based on our findings, isolation, purification and testing of the suggested active compounds could lead to novel anti-coronavirus drugs. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

The growth, adventitious bud formation, bioactive flavonoid production, antioxidant response, and cryptochrome-mediated light signal transduction in Isatis tinctoria L. hairy root cultures exposed to LED lights

The root of Isatis tinctoria L. is highly appreciated as a Traditional Chinese herbal medicine for the prevention and adjuvant treatment of respiratory diseases caused by coronaviruses viruses such as SARS and COVID-19. I. tinctoria hairy root cultures (ITHRCs) provide a better alternative to field cultivation for the production of antiviral flavonoids. For the first time, ITHRCs were exposed to different colors of LED lights i.e., red, green, blue, red/green/blue (1/1/1, RGB), and white, in an attempt to promote the root growth and enhance the production of bioactive flavonoids. Results revealed that the biomass productivity (7.15 ± 0.63 g/L) in ITHRCs with an initial inoculum size of 0.2% cultured for 50 days under blue light increased by 1.86-fold relative to that under dark (control), and yields of rutin (320.49 ± 27.56 μg/g DW), quercetin (388.75 ± 9.17 μg/g DW), kaempferol (787.90 ± 83.43 μg/g DW), and isorhamnetin (269.11 ± 20.08 μg/g DW) increased by 4.15-fold, 9.31-fold, 9.09-fold, and 2.88-fold as compared with control, respectively. Interestingly, the emergence of adventitious buds was noticed in ITHRCs under all light treatments. Additionally, the enhanced densities of chloroplasts and root hairs were found in blue-light grown ITHRCs as against control, which might account for the elevated biomass productivity. Moreover, blue light induced oxidative stress in ITHRCs in terms of the overproduction of oxidation products and the enhancement of antioxidant enzyme activity. Furthermore, blue light significantly activated photoreceptor (CRY1) and key regulator of light signaling (HY5), thus leading to the up-regulated expression of MYB4 and structural genes (such as CHS and FLS) responsible for flavonoid biosynthesis. And, the transcriptional activation of CUC1 was likely related to the formation of adventitious buds in ITHRCs. Overall, the simple supplementation of blue LED light makes ITHRCs more attractive as plant factories for obtaining higher productivity of biomass and medicinally important flavonoids. © 2023 Elsevier B.V.

Bioactive compounds by microalgae and potentials for the management of some human disease conditions.

Microalgae biomasses are excellent sources of diverse bioactive compounds such as lipids, polysaccharides, carotenoids, vitamins, phenolics and phycobiliproteins. Large-scale production of these bioactive substances would require microalgae cultivation either in open-culture systems or closed-culture systems. Some of these bioactive compounds (such as polysaccharides, phycobiliproteins and lipids) are produced during their active growth phase. They appear to have antibacterial, antifungal, antiviral, antioxidative, anticancer, neuroprotective and chemo-preventive activities. These properties confer on microalgae the potential for use in the treatment and/or management of several neurologic and cell dysfunction-related disease conditions, including Alzheimer's disease (AD), AIDS and COVID-19, as shown in this review. Although several health benefits have been highlighted, there appears to be a consensus in the literature that the field of microalgae is still fledgling, and more research needs to be carried out to ascertain the mechanisms of action that underpin the effectiveness of microalgal compounds. In this review, two biosynthetic pathways were modeled to help elucidate the mode of action of the bioactive compounds from microalgae and their products. These are carotenoid and phycobilin proteins biosynthetic pathways. The education of the public on the importance of microalgae backed with empirical scientific evidence will go a long way to ensure that the benefits from research investigations are quickly rolled out. The potential application of these microalgae to some human disease conditions was highlighted.

Virtual screening for finding inhibitor against the main protease of SARS-Cov-2 from the FDA-approved drugs database

At the end of 2019,a new coronavirus suddenly broke out all over the world.To date, there is still no targeted medicine available for the treatment of this disease. Vaccineis essential for controlling the epidemicofSARS-CoV-2. But the effective ofvaccine was reduced because of the SARS-CoV-2constant mutation. It is gratifying that scientistuncover theinfection mechanisms of the SARS-CoV-2. The main protease of SARS-CoV-2 is highly conserved and plays an important role of the life cycle of virus. Therefore, we executed virtual screening on the FDA-approved database and hoped to find a potential candidate against the main protease. As a result, we obtained eight available active compounds derived from the database through molecular dynamics simulations. As antiviral treatment candidates, the drugs can also be used to clinical emergencies. © 2022 SPIE. All rights reserved.

Regulation of Cholesterol Metabolism by Phytochemicals Derived from Algae and Edible Mushrooms in Non-Alcoholic Fatty Liver Disease.

Cholesterol synthesis occurs in almost all cells, but mainly in hepatocytes in the liver. Cholesterol is garnering increasing attention for its central role in various metabolic diseases. In addition, cholesterol is one of the most essential elements for cells as both a structural source and a player participating in various metabolic pathways. Accurate regulation of cholesterol is necessary for the proper metabolism of fats in the body. Disturbances in cholesterol homeostasis have been linked to various metabolic diseases, such as hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). For many years, the use of synthetic chemical drugs has been effective against many health conditions. Furthermore, from ancient to modern times, various plant-based drugs have been considered local medicines, playing important roles in human health. Phytochemicals are bioactive natural compounds that are derived from medicinal plants, fruit, vegetables, roots, leaves, and flowers and are used to treat a variety of diseases. They include flavonoids, carotenoids, polyphenols, polysaccharides, vitamins, and more. Many of these compounds have been proven to have antioxidant, anti-inflammatory, antiobesity and antihypercholesteremic activity. The multifaceted role of phytochemicals may provide health benefits to humans with regard to the treatment and control of cholesterol metabolism and the diseases associated with this disorder, such as NAFLD. In recent years, global environmental climate change, the COVID-19 pandemic, the current war in Europe, and other conflicts have threatened food security and human nutrition worldwide. This further emphasizes the urgent need for sustainable sources of functional phytochemicals to be included in the food industry and dietary habits. This review summarizes the latest findings on selected phytochemicals from sustainable sources-algae and edible mushrooms-that affect the synthesis and metabolism of cholesterol and improve or prevent NAFLD.

Propolis: Its Role and Efficacy in Human Health and Diseases.

With technological advancements in the medicinal and pharmaceutical industries, numerous research studies have focused on the propolis produced by stingless bees (Meliponini tribe) and Apis mellifera honeybees as alternative complementary medicines for the potential treatment of various acute and chronic diseases. Propolis can be found in tropical and subtropical forests throughout the world. The composition of phytochemical constituents in propolis varies depending on the bee species, geographical location, botanical source, and environmental conditions. Typically, propolis contains lipid, beeswax, essential oils, pollen, and organic components. The latter include flavonoids, phenolic compounds, polyphenols, terpenes, terpenoids, coumarins, steroids, amino acids, and aromatic acids. The biologically active constituents of propolis, which include countless organic compounds such as artepillin C, caffeic acid, caffeic acid phenethyl ester, apigenin, chrysin, galangin, kaempferol, luteolin, genistein, naringin, pinocembrin, coumaric acid, and quercetin, have a broad spectrum of biological and therapeutic properties such as antidiabetic, anti-inflammatory, antioxidant, anticancer, rheumatoid arthritis, chronic obstruct pulmonary disorders, cardiovascular diseases, respiratory tract-related diseases, gastrointestinal disorders, as well as neuroprotective, immunomodulatory, and immuno-inflammatory agents. Therefore, this review aims to provide a summary of recent studies on the role of propolis, its constituents, its biologically active compounds, and their efficacy in the medicinal and pharmaceutical treatment of chronic diseases.

Truths and myths about superfoods in the era of the COVID-19 pandemic.

Nowadays, during the current COVID-19 pandemic, consumers increasingly seek foods that not only fulfill the basic need (i.e., satisfying hunger) but also enhance human health and well-being. As a result, more attention has been given to some kinds of foods, termed "superfoods," making big claims about their richness in valuable nutrients and bioactive compounds as well as their capability to prevent illness, reinforcing the human immune system, and improve overall health.This review is an attempt to uncover truths and myths about superfoods by giving examples of the most popular foods (e.g., berries, pomegranates, watermelon, olive, green tea, several seeds and nuts, honey, salmon, and camel milk, among many others) that are commonly reported as having unique nutritional, nutraceutical, and functional characteristics.While superfoods have become a popular buzzword in blog articles and social media posts, scientific publications are still relatively marginal. The reviewed findings show that COVID-19 has become a significant driver for superfoods consumption. Food Industry 4.0 innovations have revolutionized many sectors of food technologies, including the manufacturing of functional foods, offering new opportunities to improve the sensory and nutritional quality of such foods. Although many food products have been considered superfoods and intensively sought by consumers, scientific evidence for their beneficial effectiveness and their "superpower" are yet to be provided. Therefore, more research and collaboration between researchers, industry, consumers, and policymakers are still needed to differentiate facts from marketing gimmicks and promote human health and nutrition.

Therapeutic capability of five active compounds in typical African medicinal plants against main proteases of SARS-CoV-2 by computational approach.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a pandemic cause of Corona Virus Disease (COVID-19), that has claimed numerous human lives across the globe. Main protease being the active protein of SARS-CoV-2 requires urgent mitigating effect against the spread of the virus. The therapeutic roles of the active compounds present in ten typical African medicinal plants were investigated in this study. Five active compounds Curcuma longa (Curcumin and Bisdethoxy curcumin), Garcinia kola (kolaviron), Zingiber officinale (Gingerol) and Vernonia amygdalina (Artemisinin) were selected and docked against Main protease through receptor grid generation, protein ligand docking, receptor ligand complex pharmacophore and binding free energy. The results obtained revealed Curcumin had the highest binding score of -8.628 kcal/mol while artermisinin presented the least with -4.123 kcal/mol. The outcome of the pharmacokinetic prediction in this study revealed high transport capacity across the gastrointestinal tract and high blood brain barrier permeability for curcumin, bisdemethoxy curcumin, gingerol and artemisinin. The exemption is gingerol with low LD50 value (250 mg/kg), the LD50 of all active compounds ranged from 2000 to 4228 mg/kg. Adsorption, distribution, metabolism, excretion and toxicity (ADMET) properties exhibited by all compounds portrayed them as non-hepatotoxic, non-cytotoxic, non-mutagenic and non-carcinogenic. The active compounds exhibited drug-likeness features against Main protease of Covid-19.

Occurrence of Pharmaceutically Active Compounds and Potential Ecological Risks in Wastewater from Hospitals and Receiving Waters in Sri Lanka.

The presence of pharmaceutically active compounds (PACs) in the environment and their associated hazards is a major global health concern; however, data on these compounds are scarce in developing nations. In the present study, the existence of 39 non-antimicrobial PACs and six of their metabolites in wastewater from hospitals and adjacent surface waters in Sri Lanka was investigated from 2016 to 2018. The highest amounts of the measured chemicals, including the highest concentrations of atorvastatin (14,620 ng/L) and two metabolites, mefenamic acid (12,120 ng/L) and o-desmethyl tramadol (8700 ng/L), were detected in wastewater from the largest facility. Mefenamic acid, gemfibrozil, losartan, cetirizine, carbamazepine, and phenytoin were detected in all the samples. The removal rates in wastewater treatment were 100% for zolpidem, norsertaline, quetiapine, chlorpromazine, and alprazolam. There was substantial variation in removal rates of PACs among facilities, and the overall data suggest that treatment processes in facilities were ineffective and that some PAC concentrations in the effluents were increased. The estimated risk quotients revealed that 14 PACs detected in water samples could pose low to high ecological risk to various aquatic organisms. Compounds such as ibuprofen, tramadol, and chlorpromazine detected in untreated and treated wastewater at these facilities pose a high risk to several aquatic organisms. Our study provides novel monitoring data for non-antimicrobial PAC abundance and the associated potential ecological risk related to hospitals and urban surface waters in Sri Lanka and further offers valuable information on pre-COVID-19 era PAC distribution in the country. Environ Toxicol Chem 2022;41:298-311. © 2021 SETAC.

An in Silico Study of the Cathepsin L Inhibitory Activity of Bioactive Compounds in Stachytarpheta jamaicensis as a Covid-19 Drug Therapy

Inhibition of cathepsin L (Cat L) can be considered a target for COVID -19 treatment. Starchytapheta jamaicensis is a plant from the Verbenaceae family that is commonly used for medicinal purposes. This study aims to analyze the inhibitory activities of compounds of Stachytarpheta jamaicensis toward Cat L by computational docking analysis. Ten compounds contained in the extracts (i.e., alpha-spinasterol, apigenin, luteolo1-7-glucuronide, friedelin, hispidulin, chlorogenic acid, ipolamiide, geraniol, hentriacontane, and gamma-aminobutyric acid) were selected as ligands;decanoyl-arg-val-lys-argchloromethylketone and oxocarbazate were used as the reference. Computational docking analysis was performed using Autodock Vina integrated into PyRx 8.0 and visualized using the Discovery Studio Visualizer v19.1.0.18287 (2019 version) based on the scoring functions. Seven bioactive compounds were bound more strongly than decanoyl-arg-val-lys-argchloromethylketone: alpha-spinasterol, apigenin, luteolol-7-glucuronide, friedelin, hispidulin, chlorogenic acid, and ipolamiide. However, all bioactive compounds were bound with less strength than oxocarbazate. Apigenin showed the best affinity, with much hydrogen bonding, and had the same ASN18 residue as Cat L inhibitor 1. Pre ADMET showed that all compounds of S. jamaicensis did not have hepatotoxicity, mutagenic, and carcinogenic criteria. The current research indicates that S. jamaicensis compounds can be used as an inhibitor for Cat L and as a COVID-19 drug candidate.

Functionality of nanomaterials and its technological aspects - Used in preventing, diagnosing and treating COVID-19.

COVID-19 (Coronavirus) has severely affected the life of human beings since December 2019. Many difficulties are faced by human beings to prevent the spread of the corona virus. However, this unexpected evolution of COVID-19 has also thrown many challenges to scientists and researchers so as to develop technologies that can be used to combat COVID-19. In the effort to combat COVID-19, many research universities and academic laboratories are also contributing by developing many technologies like Facing masks, hand sanitizers, hand washing machines, etc., to control and prevent the spread of COVID-19 disease. The use of Nano-materials is proving to be very effective in prevention, detection and diagnosis of COVID-19. In this paper many such technologies that are used to combat COVID-19 are also discussed. Some of the technologies like the germ trap technology used in face masks and hoods are also discussed. The use of nano-coatings, nano materials like graphene and carbon nano materials is playing a key role in preventing the spread of the virus. Antimicrobial nano-materials like silver nanoparticles are also effectively contributing to preventing the spread of the virus. Nano bio-sensors and gold nanoparticles are used in RT-PCR (Reverse transcription polymerase chain reaction) testing devices which are used for detection of coronavirus. The use of many nano chemicals and compounds has helped in making vaccines and anti-viral drugs that are today showing a way to safeguard human beings against the attack of this deadly virus.

COVID-19 Prophylaxis Efforts Based on Natural Antiviral Plant Extracts and Their Compounds.

During the time of the novel coronavirus disease 2019 (COVID-19) pandemic, it has been crucial to search for novel antiviral drugs from plants and well as other natural sources as alternatives for prophylaxis. This work reviews the antiviral potential of plant extracts, and the results of previous research for the treatment and prophylaxis of coronavirus disease and previous kinds of representative coronaviruses group. Detailed descriptions of medicinal herbs and crops based on their origin native area, plant parts used, and their antiviral potentials have been conducted. The possible role of plant-derived natural antiviral compounds for the development of plant-based drugs against coronavirus has been described. To identify useful scientific trends, VOSviewer visualization of presented scientific data analysis was used.

Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods.

BACKGROUND AND AIM: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods. EXPERIMENTAL PROCEDURE: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected. RESULTS AND CONCLUSION: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19. TAXONOMY CLASSIFICATION BY EVISE: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.

A review on hospital wastewater treatment: A special emphasis on occurrence and removal of pharmaceutically active compounds, resistant microorganisms, and SARS-CoV-2.

The hospital wastewater imposes a potent threat to the security of human health concerning its high vulnerability towards the outbreak of several diseases. Furthermore, the outbreak of COVID-19 pandemic demanded a global attention towards monitoring viruses and other infectious pathogens in hospital wastewater and their removal. Apart from that, the presence of various recalcitrant organics, pharmaceutically active compounds (PhACs), etc. imparts a complex pollution load to water resources and ecosystem. In this review, an insight into the occurrence, persistence and removal of drug-resistant microorganisms and infectious viruses as well as other micro-pollutants have been documented. The performance of various pilot/full-scale studies have been evaluated in terms of removal of biochemical oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS), PhACs, pathogens, etc. It was found that many biological processes, such as membrane bioreactor, activated sludge process, constructed wetlands, etc. provided more than 80% removal of BOD, COD, TSS, etc. However, the removal of several recalcitrant organic pollutants are less responsive to those processes and demands the application of tertiary treatments, such as adsorption, ozone treatment, UV treatment, etc. Antibiotic-resistant microorganisms, viruses were found to be persistent even after the treatment of hospital wastewater, and high dose of chlorination or UV treatment was required to inactivate them. This article circumscribes the various emerging technologies, which have been used to treat PhACs and pathogens. The present review also emphasized the global concern of the presence of SARS-CoV-2 RNA in hospital wastewater and its removal by the existing treatment facilities.

COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks.

In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the success of therapy to date. Neither an antiviral nor an immunomodulatory therapy in patients with SARS-CoV-2 infection/COVID-19 or pre-exposure prophylaxis against SARS-CoV-2 has proved to be effective. In this review, we try to close the gap and point out the likely relationships among lysosomotropism, increasing lysosomal pH, SARS-CoV-2 infection, and disease process, and we deduce an approach for the treatment and prophylaxis of COVID-19, and cytokine release syndrome (CRS)/cytokine storm triggered by bacteria or viruses. Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation. As supported by recent clinical data, patients who have already taken lysosomotropic drugs for other pre-existing conditions likely benefit from this treatment in the COVID-19 pandemic. The early administration of a combination of antivirals such as remdesivir and lysosomotropic drugs, such as the antibiotics teicoplanin or dalbavancin, seems to be able to prevent SARS-CoV-2 infection and transition to COVID-19.