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Ayoup MS, Eltaweil AS, Omer AM, Abd El-Monaem EM. Zwitterionic MOF-embedded alginate beads with polydopamine surface functionalization for efficient doxycycline removal: Optimization and mechanistic study. Int J Biol Macromol 2024; 281:136288. [PMID: 39368583 DOI: 10.1016/j.ijbiomac.2024.136288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/22/2024] [Accepted: 10/02/2024] [Indexed: 10/07/2024]
Abstract
The adsorptive removal of amphoteric antibiotics like doxycycline (DOX) is a difficult task because of the electrostatic repulsion between these amphoteric molecules and adsorbents. For this purpose, a zwitter adsorbent was fabricated by incorporating zwitter ZIF-67/MIL-88A binary MOF into the matrix of alginate (Alg); in addition, the surface of the beads was modified by polydopamine (PDA). The batch experiments implied the super-high adsorption efficacy of ZIF-67/MIL-88A@Alg@PDA toward DOX attained 384.61 ± 5.08 mg/g at a neutral pH medium, 25 °C, and using 0.02 g. The isotherm analysis implied the physisorption of DOX onto ZIF-67/MIL-88A@Alg@PDA, while the kinetic analysis denoted the chemisorption of DOX. The results of XPS, Zeta potential, and Lab experiments identified the types of physical and chemical interactions between ZIF-67/MIL-88A@Alg@PDA and DOX. The durability of the ZIF-67/MIL-88A@Alg@PDA beads was inspected by the recycling test, clarifying that the DOX adsorption aptitude declined by 12.22 mg/g. In addition, the measured leaching concentrations of cobalt and iron from the leaching test were 0.008 and 0.098 mg/L. The ionic strength of ZIF-67/MIL-88A@Alg@PDA, implying an enhancement in the DOX removal (%) from 83.51 to 93.50 % by raising the NaCl concentration from 0.2 to 1.0 mol/L. Therefore, our study could provide a simple procedure to overcome the electrostatic repulsion that retard the adsorption process of the amphoteric drugs onto charged adsorbents with positive or negative charges. Additionally, this procedure could also generate an electrostatic interaction between the zwitter adsorbents and the amphoteric drugs at specific pH media when they are in a zwitterionic nature.
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Affiliation(s)
- Mohammed Salah Ayoup
- Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
| | - Abdelazeem S Eltaweil
- Department of Engineering, College of Engineering and Technology, University of Technology and Applied Sciences, Ibra, Sultanate of Oman; Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
| | - Ahmed M Omer
- Polymer Institute of the Slovak Academy of Sciences, Dúbravská Cesta 9, 845 41 Bratislava, Slovakia; Polymer Materials Research Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab City, P. O. Box: 21934, Alexandria, Egypt
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2
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Abdelsamie AS, Hamed MM, Schütz C, Röhrig T, Kany AM, Schmelz S, Blankenfeldt W, Hirsch AKH, Hartmann RW, Empting M. Discovery and optimization of thiazole-based quorum sensing inhibitors as potent blockers of Pseudomonas aeruginosa pathogenicity. Eur J Med Chem 2024; 276:116685. [PMID: 39042991 DOI: 10.1016/j.ejmech.2024.116685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 07/12/2024] [Accepted: 07/12/2024] [Indexed: 07/25/2024]
Abstract
Pseudomonas aeruginosa causes life-threatening infections especially in hospitalized patients and shows an increasing resistance to established antibiotics. A process known as quorum sensing (QS) enables the pathogen to collectively adapt to various environmental conditions. Disrupting this cell-to-cell communication machinery by small-molecular entities leads to a blockade of bacterial pathogenicity. We aim to devise QS inhibitors acting on the PA-specific PQS QS system via the signal-molecule receptor and transcriptional regulator PqsR (MvfR). In this manuscript, we describe the further optimization of PqsR inverse agonists by broadening the structural space of a previously described triazole-bearing lead compound and arriving at highly potent thiazole derivatives with activities against P. aeruginosa virulence factor pyocyanin in the nanomolar range. All new derivatives were profiled regarding biological activity as well as in vitro ADMET parameters. Additionally, we assessed safety-pharmacology characteristics of the two most promising compounds both bearing a 3-chloro-4-isopropoxyphenyl motive. Demonstrating an overall favorable profile, our new PqsR inverse agonists represent a valuable addition as optimized lead compounds, enabling preclinical development of P. aeruginosa-specific pathoblockers.
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Affiliation(s)
- Ahmed S Abdelsamie
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany; Department of Chemistry of Natural and Microbial Products, Institute of Pharmaceutical and Drug Industries Research, National Research Centre, El-Buhouth St., Dokki, P.O. Box 12622, Cairo, Egypt
| | - Mostafa M Hamed
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany
| | - Christian Schütz
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany
| | - Teresa Röhrig
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany
| | - Andreas M Kany
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany
| | - Stefan Schmelz
- Department of Structure and Function of Proteins (SFPR), Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Wulf Blankenfeldt
- Department of Structure and Function of Proteins (SFPR), Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Anna K H Hirsch
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany
| | - Rolf W Hartmann
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany
| | - Martin Empting
- Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Saarland University, Department of Pharmacy, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany.
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Chakraborty A, Ghosh R, Soumya Mohapatra S, Barik S, Biswas A, Chowdhuri S. Repurposing of antimycobacterium drugs for COVID-19 treatment by targeting SARS CoV-2 main protease: An in-silico perspective. Gene 2024; 922:148553. [PMID: 38734190 DOI: 10.1016/j.gene.2024.148553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/27/2024] [Accepted: 05/08/2024] [Indexed: 05/13/2024]
Abstract
The global mortality rate has been significantly impacted by the COVID-19 pandemic, caused by the SARS CoV-2 virus. Although the pursuit for a potent antiviral is still in progress, experimental therapies based on repurposing of existing drugs is being attempted. One important therapeutic target for COVID-19 is the main protease (Mpro) that cleaves the viral polyprotein in its replication process. Recently minocycline, an antimycobacterium drug, has been successfully implemented for the treatment of COVID-19 patients. But it's mode of action is still far from clear. Furthermore, it remains unresolved whether alternative antimycobacterium drugs can effectively regulate SARS CoV-2 by inhibiting the enzymatic activity of Mpro. To comprehend these facets, eight well-established antimycobacterium drugs were put through molecular docking experiments. Four of the antimycobacterium drugs (minocycline, rifampicin, clofazimine and ofloxacin) were selected by comparing their binding affinities towards Mpro. All of the four drugs interacted with both the catalytic residues of Mpro (His41 and Cys145). Additionally, molecular dynamics experiments demonstrated that the Mpro-minocyline complex has enhanced stability, experiences reduced conformational fluctuations and greater compactness than other three Mpro-antimycobacterium and Mpro-N3/lopinavir complexes. This research furnishes evidences for implementation of minocycline against SARS CoV-2. In addition, our findings also indicate other three antimycobacterium/antituberculosis drugs (rifampicin, clofazimine and ofloxacin) could potentially be evaluated for COVID-19 therapy.
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Affiliation(s)
- Ayon Chakraborty
- University Institute of Biotechnology, University Centre for Research & Development, Chandigarh University, Mohali, India
| | - Rajesh Ghosh
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India
| | | | - Subhashree Barik
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India
| | - Ashis Biswas
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
| | - Snehasis Chowdhuri
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
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Rezaei A, Moqadami A, Khalaj-Kondori M. Minocycline as a prospective therapeutic agent for cancer and non-cancer diseases: a scoping review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2835-2848. [PMID: 37991540 DOI: 10.1007/s00210-023-02839-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 11/05/2023] [Indexed: 11/23/2023]
Abstract
Minocycline is an FDA-approved secondary-generation tetracycline antibiotic. It is a synthetic antibiotic having many biological effects, such as antioxidant, anti-inflammatory, anti-cancer, and neuroprotective functions. This study discusses the pharmacological mechanisms of preventive and therapeutic effects of minocycline. Specifically, it provides a comprehensive overview of the molecular pathways by which minocycline acts on the different cancers, including ovarian, breast, glioma, colorectal, liver, pancreatic, lung, prostate, melanoma, head and neck, leukemia, and non-cancer diseases such as Alzheimer's disease, Parkinson, schizophrenia, multiple sclerosis, Huntington, polycystic ovary syndrome, and coronavirus disease 19. Minocycline may be a potential medication for these disorders due to its strong blood-brain barrier penetrance. It is also widely accepted as a specific medication, has a well-known side-effect characteristic, is reasonably priced, making it appropriate for continuous use in managing diseases, and has been demonstrated as an oral approach because it is effectively absorbed and accomplished almost all of the body's parts.
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Affiliation(s)
- Abedeh Rezaei
- Department of Animal Biology¸ Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Amin Moqadami
- Department of Animal Biology¸ Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Mohammad Khalaj-Kondori
- Department of Animal Biology¸ Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
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Zang Akono AR, Blaise N, Valery HG. Preparation of a Carbon paste electrode with Active materials for the detection of Tetracycline. Heliyon 2024; 10:e28471. [PMID: 38560244 PMCID: PMC10981106 DOI: 10.1016/j.heliyon.2024.e28471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 04/04/2024] Open
Abstract
The Electrochemical sensor based on carbon-clay paste electrode (CCPE) was constructed for sensitive determination of Tetracycline (Tc). The mineralogical composition, morphology, structure and performance of CCPE were characterized using X-ray diffraction powder, Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Cyclic Voltammetry analysis. The CCPE is constituted of two types of clay having the ratio 1/1 and 2/1 characteristic of kaolinite and montmorillonite clay respectively. Its porous structure is ascribed to the presence of graphite. The CCPE exhibited a good electrocatalytic activity towards the oxidation of Tc. The electrochemical kinetics and mechanism of Tc were proposed, showing that Tc electrocatalytic oxidation reaction was controlled by diffusion process and took place in three steps. A low concentration of Tc was detected by amperometry with the linear ranges of 0.5μM-0.8 μM (R2 = 0.98), the sensitivity was 8.01 μA/μM.cm2, the limit of detection and quantification were 5.16x10-3μM(S/N = 3) and 1.72x10-2μM respectively. Thus, the proposed electrode provides a promising and prospective CCPE sensing platform for the detection of Tc in the environment.
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Affiliation(s)
| | - Niraka Blaise
- Department of Textile and Leather Engineering, National Advanced School of Engineering of Maroua, University of Maroua, Cameroon
| | - Hambate Gomdje Valery
- Department of Textile and Leather Engineering, National Advanced School of Engineering of Maroua, University of Maroua, Cameroon
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Sudewi S, Li CH, Chabib L, Rasool A, Arputharaj E, Zulfajri M, Huang GG. Turn-off/turn-on biosensing of tetracycline and ciprofloxacin antibiotics using fluorescent iron oxide quantum dots. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:1261-1271. [PMID: 38323472 DOI: 10.1039/d3ay02168h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
A fluorescence probe based on iron oxide quantum dots (IO-QDs) was synthesized using the hydrothermal method for the determination of tetracycline (TCy) and ciprofloxacin (CPx) in aqueous solution. The IO-QDs were characterized using high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (P-XRD), vibrating sample magnetometry (VSM), and Fourier-transform infrared spectroscopy (FTIR). The as-prepared IO-QDs are fluorescent, stable, and with a fluorescence quantum yield (QY) of 9.8 ± 0.12%. The fluorescence of IO-QDs was observed to be quenched and enhanced in the presence of TCy and CPx, respectively. The fluorescence intensity ratio shows linearity at concentrations from 1-100 μM and 5-100 μM for TCy and CPx, respectively; the detection limit for TCy and CPx was estimated to be 0.71 μM and 1.56 μM, respectively. The proposed method was also successfully utilized in the spiked samples of drinking water and honey with good recoveries. The method offered convenience, rapid detection, high sensitivity, selectivity, and cost-efficient alternative options for the determination of TCy and CPx in real samples.
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Affiliation(s)
- Sri Sudewi
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
- Department of Pharmacy, Faculty of Mathematics and Natural Science, Universitas Sam Ratulangi, Manado 95115, Indonesia
| | - Chien-Hung Li
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Lutfi Chabib
- Pharmacy Study Program, Faculty of Mathematics and Science, Universitas Islam Indonesia, Yogyakarta 55584, Indonesia
| | - Akhtar Rasool
- Research Center for Chemistry, National Research and Innovation Agency (BRIN), KST BJ Habibie, Setu, Tangerang Selatan 15314, Indonesia
| | - Emmanuvel Arputharaj
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Muhammad Zulfajri
- Department of Chemistry Education, Universitas Serambi Mekkah, Banda Aceh 23245, Indonesia
| | - Genin Gary Huang
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
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Kumari H, Sonia, Suman, Ranga R, Chahal S, Devi S, Sharma S, Kumar S, Kumar P, Kumar S, Kumar A, Parmar R. A Review on Photocatalysis Used For Wastewater Treatment: Dye Degradation. WATER, AIR, AND SOIL POLLUTION 2023; 234:349. [PMID: 37275322 PMCID: PMC10212744 DOI: 10.1007/s11270-023-06359-9] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/09/2023] [Indexed: 06/07/2023]
Abstract
Water pollution is a global issue as a consequence of rapid industrialization and urbanization. Organic compounds which are generated from various industries produce problematic pollutants in water. Recently, metal oxide (TiO2, SnO2, CeO2, ZrO2, WO3, and ZnO)-based semiconductors have been explored as excellent photocatalysts in order to degrade organic pollutants in wastewater. However, their photocatalytic performance is limited due to their high band gap (UV range) and recombination time of photogenerated electron-hole pairs. Strategies for improving the performance of these metal oxides in the fields of photocatalysis are discussed. To improve their photocatalytic activity, researchers have investigated the concept of doping, formation of nanocomposites and core-shell nanostructures of metal oxides. Rare-earth doped metal oxides have the advantage of interacting with functional groups quickly because of the 4f empty orbitals. More precisely, in this review, in-depth procedures for synthesizing rare earth doped metal oxides and nonocomposites, their efficiency towards organic pollutants degradation and sources have been discussed. The major goal of this review article is to propose high-performing, cost-effective combined tactics with prospective benefits for future industrial applications solutions.
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Affiliation(s)
- Harita Kumari
- Present Address: Department of Physics, Maharshi Dayanand University, Rohtak, 124001 Haryana India
| | - Sonia
- Present Address: Department of Physics, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, 131039 Haryana India
| | - Suman
- Present Address: Department of Physics, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, 131039 Haryana India
| | - Rohit Ranga
- Present Address: Department of Physics, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, 131039 Haryana India
| | - Surjeet Chahal
- Materials and Nano Engineering Research Laboratory, Department of Physics, School of Physical Sciences, DIT University, Dehradun, 248009 India
| | - Seema Devi
- Department of Physics, Netaji Subhas University of Technology, New Delhi, 110078 India
| | - Sourabh Sharma
- Department of Physics, Netaji Subhas University of Technology, New Delhi, 110078 India
| | - Sandeep Kumar
- J. C. Bose University of Science and Technology, YMCA, Faridabad, 121006 Haryana India
| | - Parmod Kumar
- J. C. Bose University of Science and Technology, YMCA, Faridabad, 121006 Haryana India
| | - Suresh Kumar
- Present Address: Department of Physics, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, 131039 Haryana India
| | - Ashok Kumar
- Present Address: Department of Physics, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, 131039 Haryana India
| | - Rajesh Parmar
- Present Address: Department of Physics, Maharshi Dayanand University, Rohtak, 124001 Haryana India
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Tsuchiya H. Treatments of COVID-19-Associated Taste and Saliva Secretory Disorders. Dent J (Basel) 2023; 11:140. [PMID: 37366663 DOI: 10.3390/dj11060140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/17/2023] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Since the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, treating taste and saliva secretory disorders associated with coronavirus disease 2019 (COVID-19) has become a critical issue. The aim of the present study was to update information on treatments applicable to such oral symptoms and discuss their pathogenic mechanisms. The literature search indicated that different treatments using tetracycline, corticosteroids, zinc, stellate ganglion block, phytochemical curcumin, traditional herbal medicine, nutraceutical vitamin D, photobiomodulation, antiviral drugs, malic acid sialagogue, chewing gum, acupuncture, and/or moxibustion have potential effects on COVID-19-associated ageusia/dysgeusia/hypogeusia and xerostomia/dry mouth/hyposalivation. These treatments have multiple modes of action on viral cellular entry and replication, cell proliferation and differentiation, immunity, and/or SARS-CoV-2 infection-induced pathological conditions such as inflammation, cytokine storm, pyroptosis, neuropathy, zinc dyshomeostasis, and dysautonomia. An understanding of currently available treatment options is required for dental professionals because they may treat patients who were infected with SARS-CoV-2 or who recovered from COVID-19, and become aware of their abnormal taste and salivary secretion. By doing so, dentists and dental hygienists could play a crucial role in managing COVID-19 oral symptoms and contribute to improving the oral health-related quality of life of the relevant patients.
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Affiliation(s)
- Hironori Tsuchiya
- Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan
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Almeida A, De Mello-Sampayo C, Lopes A, Carvalho da Silva R, Viana P, Meisel L. Predicted Environmental Risk Assessment of Antimicrobials with Increased Consumption in Portugal during the COVID-19 Pandemic; The Groundwork for the Forthcoming Water Quality Survey. Antibiotics (Basel) 2023; 12:antibiotics12040652. [PMID: 37107014 PMCID: PMC10135311 DOI: 10.3390/antibiotics12040652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023] Open
Abstract
The environmental release of antimicrobial pharmaceuticals is an imminent threat due to ecological impacts and microbial resistance phenomena. The recent COVID-19 outbreak will likely lead to greater loads of antimicrobials in the environment. Thus, identifying the most used antimicrobials likely to pose environmental risks would be valuable. For that, the ambulatory and hospital consumption patterns of antimicrobials in Portugal during the COVID-19 pandemic (2020–2021) were compared with those of 2019. A predicted risk assessment screening approach based on exposure and hazard in the surface water was conducted, combining consumption, excretion rates, and ecotoxicological/microbiological endpoints in five different regions of Portugal. Among the 22 selected substances, only rifaximin and atovaquone demonstrated predicted potential ecotoxicological risks for aquatic organisms. Flucloxacillin, piperacillin, tazobactam, meropenem, ceftriaxone, fosfomycin, and metronidazole showed the most significant potential for antibiotic resistance in all analysed regions. Regarding the current screening approach and the lack of environmental data, it is advisable to consider rifaximin and atovaquone in subsequent water quality surveys. These results might support the forthcoming monitorisation of surface water quality in a post-pandemic survey.
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Affiliation(s)
- Anabela Almeida
- Centro de Investigação Vasco da Gama (CIVG), Departamento de Ciências Veterinárias, Escola Universitária Vasco da Gama (EUVG), Campus Universitário de Lordemão, 3020-210 Coimbra, Portugal
- Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Universidade de Coimbra, 3000-548 Coimbra, Portugal
- Correspondence: (A.A.); (L.M.)
| | - Cristina De Mello-Sampayo
- Laboratory of Neuroinflammation, Signaling and Neuroregeneration, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal
| | - Ana Lopes
- Agência Portuguesa do Ambiente (APA), Rua da Murgueira, 9, 2610-124 Amadora, Portugal
| | - Rita Carvalho da Silva
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal
- Biosafety Unit, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal
| | - Paula Viana
- Agência Portuguesa do Ambiente (APA), Rua da Murgueira, 9, 2610-124 Amadora, Portugal
| | - Leonor Meisel
- Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines (iMED.Ulisboa), 1600-277 Lisbon, Portugal
- Correspondence: (A.A.); (L.M.)
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10
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Sudewi S, Chabib L, Zulfajri M, Gedda G, Huang GG. Polyvinylpyrrolidone-passivated fluorescent iron oxide quantum dots for turn-off detection of tetracycline in biological fluids. J Food Drug Anal 2023; 31:177-193. [PMID: 37224556 PMCID: PMC10208663 DOI: 10.38212/2224-6614.3440] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 09/28/2022] [Indexed: 06/03/2024] Open
Abstract
Tetracycline is an antibiotic that has been prescribed for COVID-19 treatment, raising concerns about antibiotic resistance after long-term use. This study reported fluorescent polyvinylpyrrolidone-passivated iron oxide quantum dots (IO QDs) for detecting tetracycline in biological fluids for the first time. The as-prepared IO QDs have an average size of 2.84 nm and exist a good stability under different conditions. The IO QDs' tetracycline detection performance could be attributed to a combination of static quenching and inner filter effect. The IO QDs displayed high sensitivity and selectivity toward tetracycline and achieved a good linear relationship with the corresponding detection limit being 91.6 nM.
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Affiliation(s)
- Sri Sudewi
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 80708,
Taiwan
- Department of Pharmacy, Faculty of Mathematics and Natural Science, Universitas Sam Ratulangi, Manado, 95115,
Indonesia
| | - Lutfi Chabib
- Department of Pharmacy, Faculty of Mathematics and Science, Universitas Islam Indonesia, Yogyakarta, 55584,
Indonesia
| | - Muhammad Zulfajri
- Department of Chemistry Education, Universitas Serambi Mekkah, Banda Aceh, Aceh, 23245,
Indonesia
| | - Gangaraju Gedda
- Department of Chemistry, School of Engineering, Presidency University, Bangalore, 560064, Karnataka,
India
| | - Genin G. Huang
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 80708,
Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708,
Taiwan
- Department of Chemistry, National Sun Yat-sen University, Kaohsiung, 80424,
Taiwan
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11
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Mittal H, Ivaturi A, Khanuja M. MoSe 2-modified ZIF-8 novel nanocomposite for photocatalytic remediation of textile dye and antibiotic-contaminated wastewater. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:4151-4165. [PMID: 35963971 PMCID: PMC9376053 DOI: 10.1007/s11356-022-22487-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 08/07/2022] [Indexed: 06/15/2023]
Abstract
COVID-19-led antibiotic waste generated from hospitals and health centres may cause serious health issues and significantly impact the environment. In the coming decades, antibiotic resistance will be one of the most significant threats to global human health. Photocatalytic water remediation is an effective and promising environmental solution that can be utilized to address this issue, to convert antibiotic waste into non-toxic products by utilizing renewable and abundant solar energy. In the present study, a novel nanocomposite of zeolitic imidazolate frameworks (ZIF-8) and molybdenum diselenide (MoSe2) was efficiently synthesized by the solvothermal method for the complete degradation of the antibiotics and textile waste from water. The morphology, crystallinity and band gap of the samples were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and UV-visible spectroscopy. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) provide the binding information of the sample. The photocatalytic activity was tested for degradation of the antibiotics (tetracycline hydrochloride (TC) and metronidazole (MNZ)) used in COVID-19 treatment and textile dye (malachite green). Time-resolved photoluminescence spectroscopy confirmed the enhanced charge separation in the MoSe2@ZIF-8 nanocomposite with an average lifetime of 4.72 ns as compared to pristine samples. The nanocomposite showed ~ 100% removal efficiency with rate constants of 63 × 10-3, 49 × 10-3 and 42 × 10-3 min-1 for TC, MNZ and malachite green, respectively. The photocatalytic degradation of TC was carried out under different pH conditions (4, 7 and 9), and the degradation mechanism was explained on the basis of zeta potential measurements and active species trapping experiment. The by-products of the photocatalytic treatment of TC antibiotics were tested using liquid chromatography-mass spectroscopy (LC-MS), and they were found to be non-toxic for aquatic and human life. The regeneration property of the nanocomposite was confirmed by FESEM with regeneration efficiency of 88.7% in the 4th cycle. Thus, MoSe2@ZIF-8-based photocatalysts have potential application in water remediation, especially in making the antibiotic waste less toxic.
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Affiliation(s)
- Honey Mittal
- Centre for Nanoscience and Nanotechnology, Jamia Millia Islamia, New Delhi, 110025, India
| | - Aruna Ivaturi
- Smart Materials Research and Device Technology (SMaRDT) Group, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, G1 1XL, UK
| | - Manika Khanuja
- Centre for Nanoscience and Nanotechnology, Jamia Millia Islamia, New Delhi, 110025, India.
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12
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Abadi B, Ilaghi M, Shahsavani Y, Faramarzpour M, Oghazian MB, Rahimi HR. Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review. Curr Rev Clin Exp Pharmacol 2023; 18:51-63. [PMID: 34994339 DOI: 10.2174/2772432817666220106162013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/07/2021] [Accepted: 11/11/2021] [Indexed: 02/08/2023]
Abstract
In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection, as suggested by the evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting in co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of co-infection.
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Affiliation(s)
- Banafshe Abadi
- Brain Cancer Research Core (BCRC), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Mehran Ilaghi
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Department of Infectious Diseases, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Yasamin Shahsavani
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahsa Faramarzpour
- Brain Cancer Research Core (BCRC), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Bagher Oghazian
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Hamid-Reza Rahimi
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
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13
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Anand P, Verma A, Hong YA, Hu A, Jaihindh DP, Wong MS, Fu YP. Morphological and elemental tuning of BiOCl/BiVO 4 heterostructure for uric acid electrochemical sensor and antibiotic photocatalytic degradation. CHEMOSPHERE 2023; 310:136847. [PMID: 36241103 DOI: 10.1016/j.chemosphere.2022.136847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/27/2022] [Accepted: 10/08/2022] [Indexed: 06/16/2023]
Abstract
Deep eutectic solvents (DES) consisting of EG-(ChCl: C2H6O2) and TU-(ChCl: CH4N2S) assisted synthesized BiOCl/BiVO4 heterostructured catalyst studied for electrochemical uric acid (UA) sensor and tetracycline photocatalytic degradation. The chemical composition of the BiOCl/BiVO4 catalyst was analyzed by X-ray photoelectron spectroscopy (XPS). UV-vis spectroscopy reveals increased absorption of visible light till the near-infrared region, which results in a narrowing of band gap energy from 2.3 eV to 2.2 eV for BiOCl/BiVO4-TU. Morphology of catalyst analyzed using field-emission scanning electron microscope (FE-SEM) and Transmission electron microscope (TEM) technique. Time-Resolved photoluminescence (TRPL) confirms an increased lifetime of e-/h+ pair after heterostructure formation. The catalyst-modified glassy carbon electrode shows selectivity toward the detection of uric acid (UA). The limit of detection (LOD) is estimated to be 0.04688 μM for UA; also, interference and stability of catalyst were studied. Photocatalytic activity of the synthesized catalyst was investigated by degrading tetracycline (TC) antibiotic pollutants, and their intermediate product was analyzed by ion trap mass spectrometry (MS).
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Affiliation(s)
- Pandiyarajan Anand
- Department of Materials Science and Engineering, National Dong Hwa University, Shou-Feng, Hualien, 97401, Taiwan
| | - Atul Verma
- Department of Materials Science and Engineering, National Dong Hwa University, Shou-Feng, Hualien, 97401, Taiwan
| | - Yi-An Hong
- Institute of Medical Sciences, Tzu-Chi University, Hualien, 97002, Taiwan
| | - Anren Hu
- Institute of Medical Sciences, Tzu-Chi University, Hualien, 97002, Taiwan; Department of Laboratory Medicine and Biotechnology, Tzu-Chi University, Hualien, 97004, Taiwan
| | | | - Ming-Show Wong
- Department of Materials Science and Engineering, National Dong Hwa University, Shou-Feng, Hualien, 97401, Taiwan.
| | - Yen-Pei Fu
- Department of Materials Science and Engineering, National Dong Hwa University, Shou-Feng, Hualien, 97401, Taiwan.
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14
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Wu HHL, Athwal VS, Kalra PA, Chinnadurai R. COVID-19 and hepatorenal syndrome. World J Gastroenterol 2022; 28:5666-5678. [PMID: 36338894 PMCID: PMC9627428 DOI: 10.3748/wjg.v28.i39.5666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/21/2022] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - Varinder S Athwal
- Faculty of Biology, Medicine & Health (Division of Diabetes, Metabolism & Gastroenterology), The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Philip A Kalra
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
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15
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Pipitò L, Trizzino M, Ferraro D, Cascio A. Monkeypox proctitis treated with doxycycline in an HIV MSM returning to Italy from France. Travel Med Infect Dis 2022; 50:102469. [PMID: 36180023 PMCID: PMC9534081 DOI: 10.1016/j.tmaid.2022.102469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 12/05/2022]
Affiliation(s)
- Luca Pipitò
- Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties "G D'Alessandro," University of Palermo, Palermo, Italy
| | - Marcello Trizzino
- Infectious and Tropical Disease Unit, AOU Policlinico "P. Giaccone", Palermo, Italy
| | - Donatella Ferraro
- Microbiology and Virology Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties "G D'Alessandro," University of Palermo, Palermo, Italy
| | - Antonio Cascio
- Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties "G D'Alessandro," University of Palermo, Palermo, Italy.
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16
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Stambouli N, Driss A, Gargouri F, Bahrini K, Arfaoui B, Abid R, Taamallah K, Hannachi S, Boughariou S, Rebai A, Naas I, Ghanem M, Ammar H, Aichaouia C, Harrathi A, Yousfi MA, Battikh R, Moussa MB, Razgallah R, Ferjani M, Gharsallah H. COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial. Int J Infect Dis 2022; 122:553-558. [PMID: 35724828 PMCID: PMC9212900 DOI: 10.1016/j.ijid.2022.06.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/26/2022] [Accepted: 06/13/2022] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVES This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups. METHODS We conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests. RESULTS We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27). CONCLUSION Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.
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Affiliation(s)
- Nejla Stambouli
- General Directorate of Military Health,Research Unit UR17DN05, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Corresponding author:
| | - Adel Driss
- Department of Physiology, Morehouse School of Medicine, Atlanta GA, USA
| | - Faten Gargouri
- General Directorate of Military Health,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Khadija Bahrini
- Research Unit UR17DN05, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia
| | - Bilel Arfaoui
- Department of Internal Medicine, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Rim Abid
- Department of Infectious Disease, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Karima Taamallah
- Department of cardiology, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Souha Hannachi
- Department of Infectious Disease, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Sana Boughariou
- Department of Intensive Care, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Aicha Rebai
- Department of Intensive Care, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Imen Naas
- Department of Intensive Care, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Mohamed Ghanem
- Department of Gastroenterology, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | | | - Chiraz Aichaouia
- Department of Pneumology, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | | | - Mohamed Ali Yousfi
- Department of Pharmacy, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia
| | - Riadh Battikh
- Department of Infectious Disease, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Mohamed Ben Moussa
- Laboratory of Virology, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia
| | - Rabie Razgallah
- Research Unit UR17DN05, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia
| | - Mustapha Ferjani
- General Directorate of Military Health,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia
| | - Hédi Gharsallah
- Department of Intensive Care, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Research Unit UR17DN05, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia, Military Hospital of Tunis, 1008 Mont fleury, Tunis, Tunisia,Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunisia,Details of “OD-doxy-PNV-COVID-19 Trial” investigators are given in the Appendix
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17
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Alam I, Garg K, Raheja A, Tandon V, Sharma R, Singh M, Singh GP, Mishra S, Singh PK, Agrawal D, Soni KD, Suri A, Chandra PS, Kale SS. Managing Traumatic Brain Injury During the Coronavirus Disease 2019 Pandemic-A Case-Matched Controlled Analysis of Immediate Outcomes. World Neurosurg 2022; 165:e59-e73. [PMID: 35643408 PMCID: PMC9131442 DOI: 10.1016/j.wneu.2022.05.076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/17/2022] [Accepted: 05/18/2022] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The primary objective of this study was to evaluate the outcome of patients with traumatic brain injury (TBI) during the coronavirus disease 2019 (COVID-19) pandemic and to compare their outcome with case-matched controls from the prepandemic phase. METHODS This is a retrospective case-control study in which all patients with TBI admitted during COVID-19 pandemic phase (Arm A) from March 24, 2020 to November 30, 2020 were matched with age and Glasgow Coma Scale score-matched controls from the patients admitted before March 2020 (Arm B). RESULTS The total number of patients matched in each arm was 118. The length of hospital stay (8 days vs. 5 days; P < 0.001), transit time from emergency room to operation room (150 minutes vs. 97 minutes; P = 0.271), anesthesia induction time (75 minutes vs. 45 minutes; P = 0.002), and operative duration (275 minutes vs. 180 minutes; P = 0.002) were longer in arm A. Although the incidence of fever and pneumonia was significantly higher in arm A than in arm B (50% vs. 26.3%, P < 0.001 and 27.1% vs. 1.7%, P < 0.001, respectively), outcome (Glasgow Outcome Scale-Extended) and mortality (18.6% vs. 14.4% respectively; P = 0.42) were similar in both the groups. CONCLUSIONS The outcome of the patients managed for TBI during the COVID-19 pandemic was similar to matched patients with TBI managed at our center before the onset of the COVID-19 pandemic. This finding suggests that the guidelines followed during the COVID-19 pandemic were effective in dealing with patients with TBI. This model can serve as a guide for any future pandemic waves for effective management of patients with TBI without compromising their outcome.
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Affiliation(s)
- Intekhab Alam
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Kanwaljeet Garg
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Amol Raheja
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Vivek Tandon
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India,To whom correspondence should be addressed: Vivek Tandon, M.B.B.S., M.S., M.Ch
| | - Ravi Sharma
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Manmohan Singh
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Gyaninder Pal Singh
- Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | - Shashwat Mishra
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Pankaj Kumar Singh
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Agrawal
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | - Kapil Dev Soni
- Critical and Intensive Care, JPN Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Suri
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
| | | | - Shashank Sharad Kale
- Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
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18
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Kumar A, Chattopadhyay A, Gupta S. Neuropsychiatric manifestation of the drugs used in the treatment of SARS-2-CoV-2019 (COVID-19) infection and their management: An overview and practice implications. Asian J Psychiatr 2022; 73:103101. [PMID: 35461033 PMCID: PMC8986230 DOI: 10.1016/j.ajp.2022.103101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/16/2022] [Accepted: 04/02/2022] [Indexed: 12/15/2022]
Abstract
Treatment guidelines for the COVID-19 treatment are still evolving, moreover, the changing variants of the virus with varying virulence, pose challenges for the healthcare professionals (HCP) not only in managing the primary infection but also a myriad of physical and neuropsychiatric complications. The neuropsychiatric adverse consequences associated with the COVID-19 are attributable to the direct effect of the virus, secondary complications, drug-drug interaction, and neuropsychiatric manifestations of drugs used in its treatment. These neuropsychiatric manifestations not only complicate the ongoing treatment but also adversely affect the prognosis. As the treatment guidelines for the management of the COVID are still evolving, the use of non-evidence-based medications, including their off-label use, are rampant that often extend to their non-judicious or irrational use (more than the recommended dose, multiple medications, etc.). Despite the significance of the topic, literature is sparse. Knowing about the risk factors and the potential neuropsychiatric adverse effects with various anti-COVID-19 medications would help HCPs in effectively preventing, early identifying, and promptly managing these neuropsychiatric symptoms. Therefore, this narrative review is aimed to highlight the neuropsychiatric symptoms associated with medications/interventions used in the management of COVID-19 and how to manage them, especially in view of the world facing the third wave of COVID-19.
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Affiliation(s)
- Akash Kumar
- Department of Psychiatry, All India Institute of Medical Sciences, Bhopal, 462020, India.
| | - Ankita Chattopadhyay
- Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Snehil Gupta
- Department of Psychiatry, All India Institute of Medical Sciences, Bhopal, 462020, India.
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19
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Luz MS, da Silva Júnior RT, Santos de Santana GA, Rodrigues GS, Crivellaro HDL, Calmon MS, dos Santos CFSM, Silva LGDO, Ferreira QR, Mota GR, Heim H, Silva FAFD, de Brito BB, de Melo FF. Molecular and serology methods in the diagnosis of COVID-19: An overview. World J Methodol 2022; 12:83-91. [PMID: 35721247 PMCID: PMC9157626 DOI: 10.5662/wjm.v12.i3.83] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 07/31/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease-19 (COVID-19) has become a pandemic, being a global health concern since December 2019 when the first cases were reported. Severe acute respiratory syndrome coronavirus 2, the COVID-19 causal agent, is a β-coronavirus that has on its surface the spike protein, which helps in its virulence and pathogenicity towards the host. Thus, effective and applicable diagnostic methods to this disease come as an important tool for the management of the patients. The use of the molecular technique PCR, which allows the detection of the viral RNA through nasopharyngeal swabs, is considered the gold standard test for the diagnosis of COVID-19. Moreover, serological methods, such as enzyme-linked immunosorbent assays and rapid tests, are able to detect severe acute respiratory syndrome coronavirus 2-specific immunoglobulin A, immunoglobulin M, and immunoglobulin G in positive patients, being important alternative techniques for the diagnostic establishment and epidemiological surveillance. On the other hand, reverse transcription loop-mediated isothermal amplification also proved to be a useful diagnostic method for the infection, mainly because it does not require a sophisticated laboratory apparatus and has similar specificity and sensitivity to PCR. Complementarily, imaging exams provide findings of typical pneumonia, such as the ground-glass opacity radiological pattern on chest computed tomography scanning, which along with laboratory tests assist in the diagnosis of COVID-19.
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Affiliation(s)
- Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | | | | | - Gabriela Santos Rodrigues
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | - Henrique de Lima Crivellaro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | - Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | | | | | - Qesya Rodrigues Ferreira
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | - Guilherme Rabelo Mota
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | - Heloísa Heim
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | | | - Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45002175, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde , Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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20
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Salimiaghdam N, Singh L, Singh MK, Chwa M, Atilano SR, Mohtashami Z, Nesburn AB, Kuppermann BD, Lu SY, Kenney MC. Impacts of Bacteriostatic and Bactericidal Antibiotics on the Mitochondria of the Age-Related Macular Degeneration Cybrid Cell Lines. Biomolecules 2022; 12:675. [PMID: 35625603 PMCID: PMC9138285 DOI: 10.3390/biom12050675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 04/29/2022] [Accepted: 05/03/2022] [Indexed: 12/07/2022] Open
Abstract
We assessed the potential negative effects of bacteriostatic and bactericidal antibiotics on the AMD cybrid cell lines (K, U and J haplogroups). AMD cybrid cells were created and cultured in 96-well plates and treated with tetracycline (TETRA) and ciprofloxacin (CPFX) for 24 h. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔψM), cellular metabolism and ratio of apoptotic cells were measured using H2DCFDA, JC1, MTT and flow cytometry assays, respectively. Expression of genes of antioxidant enzymes, and pro-inflammatory and pro-apoptotic pathways were evaluated by quantitative real-time PCR (qRT-PCR). Higher ROS levels were found in U haplogroup cybrids when treated with CPFX 60 µg/mL concentrations, lower ΔψM of all haplogroups by CPFX 120 µg/mL, diminished cellular metabolism in all cybrids with CPFX 120 µg/mL, and higher ratio of dead cells in K and J cybrids. CPFX 120 µg/mL induced overexpression of IL-33, CASP-3 and CASP-9 in all cybrids, upregulation of TGF-β1 and SOD2 in U and J cybrids, respectively, along with decreased expression of IL-6 in J cybrids. TETRA 120 µg/mL induced decreased ROS levels in U and J cybrids, increased cellular metabolism of treated U cybrids, higher ratio of dead cells in K and J cybrids and declined ΔψM via all TETRA concentrations in all haplogroups. TETRA 120 µg/mL caused upregulation of IL-6 and CASP-3 genes in all cybrids, higher CASP-7 gene expression in K and U cybrids and downregulation of the SOD3 gene in K and U cybrids. Clinically relevant dosages of ciprofloxacin and tetracycline have potential adverse impacts on AMD cybrids possessing K, J and U mtDNA haplogroups in vitro.
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Affiliation(s)
- Nasim Salimiaghdam
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Lata Singh
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Mithalesh K. Singh
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Marilyn Chwa
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Shari R. Atilano
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Zahra Mohtashami
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Anthony B. Nesburn
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
- Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Baruch D. Kuppermann
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - Stephanie Y. Lu
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
| | - M. Cristina Kenney
- Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA; (N.S.); (L.S.); (M.K.S.); (M.C.); (S.R.A.); (Z.M.); (A.B.N.); (B.D.K.); (S.Y.L.)
- Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA 92697, USA
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21
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Abd El-Monaem EM, Eltaweil AS, Elshishini HM, Hosny M, Abou Alsoaud MM, Attia NF, El-Subruiti GM, Omer AM. Sustainable adsorptive removal of antibiotic residues by chitosan composites: An insight into current developments and future recommendations. ARAB J CHEM 2022; 15:103743. [PMID: 35126797 PMCID: PMC8800501 DOI: 10.1016/j.arabjc.2022.103743] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/24/2022] [Indexed: 01/25/2023] Open
Abstract
During COVID-19 crisis, water pollution caused by pharmaceutical residuals have enormously aggravated since millions of patients worldwide are consuming tons of drugs daily. Antibiotics are the preponderance pharmaceutical pollutants in water bodies that surely cause a real threat to human life and ecosystems. The excellent characteristics of chitosan such as nontoxicity, easy functionality, biodegradability, availability in nature and the abundant hydroxyl and amine groups onto its backbone make it a promising adsorbent. Herein, we aimed to provide a comprehensive overview of recent published research papers regarding the removal of antibiotics by chitosan composite-based adsorbents. The structure, ionic form, optimum removal pH and λmax of the most common antibiotics including Tetracycline, Ciprofloxacin, Amoxicillin, Levofloxacin, Ceftriaxone, Erythromycin, Norfloxacin, Ofloxacin, Doxycycline, Cefotaxime and Sulfamethoxazole were summarized. The development of chitosan composite-based adsorbents in order to enhance their adsorption capacity, reusability and validity were presented. Moreover, the adsorption mechanisms of these antibiotics were explored to provide more information about adsorbate-adsorbent interactions. Besides the dominant factors on the adsorption process including pH, dosage, coexisting ions, etc. were discussed. Moreover, conclusions and future recommendations are provided to inspire for further researches.
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Affiliation(s)
- Eman M Abd El-Monaem
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | | | - Hala M Elshishini
- Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, 163, Horrya Avenue, Alexandria, Egypt
| | - Mohamed Hosny
- Green Technology Group, Environmental Sciences Department, Faculty of Science, Alexandria University, 21511 Alexandria, Egypt
| | - Mohamed M Abou Alsoaud
- Polymer Materials Research Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab City, P.O. Box: 21934, Alexandria, Egypt
| | - Nour F Attia
- Fire Protection Laboratory, Chemistry Division, National Institute for Standards, 136, Giza 12211, Egypt
| | - Gehan M El-Subruiti
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Ahmed M Omer
- Polymer Materials Research Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab City, P.O. Box: 21934, Alexandria, Egypt
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22
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Yang Y, Ji W, Li X, Lin H, Chen H, Bi F, Zheng Z, Xu J, Zhang X. Insights into the mechanism of enhanced peroxymonosulfate degraded tetracycline using metal organic framework derived carbonyl modified carbon-coated Fe 0. JOURNAL OF HAZARDOUS MATERIALS 2022; 424:127640. [PMID: 34753650 DOI: 10.1016/j.jhazmat.2021.127640] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 06/13/2023]
Abstract
Tetracycline (TC) is a commonly used antibiotic that has gained wide spread notoriety owing to its high environmental risks. In this study, rich carbonyl-modified carbon-coated Fe0 was obtained by pyrolysis of MIL-100(Fe) in an Ar atmosphere, and used to activate peroxymonosulfate (PMS) for the degradation of tetracycline in water. The roles of Fe0, carbon and surface carbonyl on PMS activation were investigated. Fe0 continuously activated PMS, acted as a sustained-release source of Fe2+, and could effectively activate PMS to produce SO4•-, O2•- and •OH. Carbon was found to do responsible for electron transportation during the activation of PMS and slow down the oxidation of Fe0. The carbonyl group on the carbon surface layer was the active site of 1O2, which explains the enhanced performance for TC degradation. When Ca = 0.1 g/L and C0 = 0.4 mM, TC degradation rate reached 96%, which was attributed to the synergistic effect of radicals (i.e., SO4•-, O2•-, •OH) and non-radical (i.e., 1O2). Finally, the degradation pathway was proposed by combining density functional theory (DFT) calculations with liquid chromatography-mass spectrometry (LC-MS), toxicities of the intermediate products were also evaluated. All results show that carbonyl-modified carbon-coated Fe0 possesses promising capacity for the removal of antibiotics from water.
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Affiliation(s)
- Yiqiong Yang
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Wenqing Ji
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Xingyu Li
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Huidong Lin
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Hongjia Chen
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Fukun Bi
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Zenghui Zheng
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Jingcheng Xu
- School of Materials Science and Engineering, University of Shanghai for Science and Technology, 516 Jun Gong Road, Shanghai 200093, China
| | - Xiaodong Zhang
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China.
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23
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Drug repurposing for SARS-CoV-2 (COVID-19) treatment. CORONAVIRUS DRUG DISCOVERY 2022. [PMCID: PMC9217734 DOI: 10.1016/b978-0-323-85156-5.00027-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Drug repurposing involves the process of investigating already existing drugs with an aim to use them for different therapeutic purposes than the intended one. This approach is relatively faster, less costly, and reliable in terms of safety as the drug under study is already derisked and known for its other chemistry and pharmacokinetic properties. With these benefits in mind, it is a very reliable way to undertake drug development for emerging diseases such as COVID-19 which demand immediate interventions to slow or completely stop its havoc on mankind. One of the biggest challenges that drug repurposing has is the possibility of the occurrence of new mechanisms of action between the drug ligand and some proteins in the human physiology. Drug repurposing appears to have settled in the meantime in drug development, though more studies in the future will be warranted particularly in regards to resistance.
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24
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Li G, Row KH. Single-drop microextraction technique for the determination of antibiotics in environmental water. J Sep Sci 2021; 45:883-895. [PMID: 34919334 DOI: 10.1002/jssc.202100682] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 12/03/2021] [Accepted: 12/05/2021] [Indexed: 12/12/2022]
Abstract
Growing concerns related to antibiotic residues in environmental water have encouraged the development of rapid, sensitive, and accurate analytical methods. Single-drop microextraction has been recognized as an efficient approach for the isolation and preconcentration of several analytes from a complex sample matrix. Thus, single-drop microextraction techniques are cost-effective and less harmful to the environment, subscribing to green analytical chemistry principles. Herein, an overview and the current advances in single-drop microextraction for the determination of antibiotics in environmental water are presented were included. In particular, two main approaches used to perform single-drop microextraction (direct immersion-single-drop microextraction and headspace-single-drop microextraction) are reviewed. Furthermore, the impressive analytical features and future perspectives of single-drop microextraction are discussed in this review. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Guizhen Li
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, Shandong, 276005, P. R. China
| | - Kyung Ho Row
- Department of Chemistry and Chemical Engineering, Inha University, Incheon, 402751, Korea
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Paula HSC, Santiago SB, Araújo LA, Pedroso CF, Marinho TA, Gonçalves IAJ, Santos TAP, Pinheiro RS, Oliveira GA, Batista KA. An overview on the current available treatment for COVID-19 and the impact of antibiotic administration during the pandemic. Braz J Med Biol Res 2021; 55:e11631. [PMID: 34909910 PMCID: PMC8851906 DOI: 10.1590/1414-431x2021e11631] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 10/06/2021] [Indexed: 12/15/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused several problems in healthcare systems around the world, as to date, there is no effective and specific treatment against all forms of COVID-19. Currently, drugs with therapeutic potential are being tested, including antiviral, anti-inflammatory, anti-malarial, immunotherapy, and antibiotics. Although antibiotics have no direct effect on viral infections, they are often used against secondary bacterial infections, or even as empiric treatment to reduce viral load, infection, and replication of coronaviruses. However, there are many concerns about this therapeutic approach as it may accelerate and/or increase the long-term rates of antimicrobial resistance (AMR). We focused this overview on exploring candidate drugs for COVID-19 therapy, including antibiotics, considering the lack of specific treatment and that it is unclear whether the widespread use of antibiotics in the treatment of COVID-19 has implications for the emergence and transmission of multidrug-resistant bacteria.
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Affiliation(s)
- H S C Paula
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - S B Santiago
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - L A Araújo
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - C F Pedroso
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - T A Marinho
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - I A J Gonçalves
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - T A P Santos
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - R S Pinheiro
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
| | - G A Oliveira
- Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Valparaíso, Valparaíso, GO, Brasil
| | - K A Batista
- Departamento de Áreas Acadêmicas, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Campus Goiânia Oeste, Goiânia, GO, Brasil
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Omer AM, Abd El-Monaem EM, El-Subruiti GM, Abd El-Latif MM, Eltaweil AS. Fabrication of easy separable and reusable MIL-125(Ti)/MIL-53(Fe) binary MOF/CNT/Alginate composite microbeads for tetracycline removal from water bodies. Sci Rep 2021; 11:23818. [PMID: 34893701 PMCID: PMC8664953 DOI: 10.1038/s41598-021-03428-z] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 11/30/2021] [Indexed: 01/17/2023] Open
Abstract
In this investigation, we aimed to fabricate easy separable composite microbeads for efficient adsorption of tetracycline (TC) drug. MIL-125(Ti)/MIL-53(Fe) binary metal organic framework (MOF) was synthetized and incorporated with carbon nanotube (CNT) into alginate (Alg) microbeads to form MIL-125(Ti)/MIL-53(Fe)/CNT@Alg composite microbeads. Various tools including FTIR, XRD, SEM, BET, Zeta potential and XPS were applied to characterize the composite microbeads. It was found that the specific surface area of MIL-125(Ti)/MIL-53(Fe)/CNT@Alg microbeads was 273.77 m2/g. The results revealed that the adsorption of TC augmented with rising CNT proportion up to 15 wt% in the microbeads matrix. In addition, the adsorption process followed the pseudo-second-order and well-fitted to Freundlich and Langmuir models with a maximum adsorption capacity of 294.12 mg/g at 25 ◦C and pH 6. Furthermore, thermodynamic study clarified that the TC adsorption process was endothermic, random and spontaneous. Besides, reusability test signified that MIL-125(Ti)/MIL-53(Fe)/CNT@Alg composite microbeads retained superb adsorption properties for six consecutive cycles, emphasizing its potentiality for removing of pharmaceutical residues.
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Affiliation(s)
- Ahmed M Omer
- Polymer Materials Research Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), P. O. Box: 21934, New Borg El-Arab City, Alexandria, Egypt.
| | - Eman M Abd El-Monaem
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
| | - Gehan M El-Subruiti
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Mona M Abd El-Latif
- Fabrication Technology Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), P. O. Box: 21934, New Borg El-Arab City, Alexandria, Egypt
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27
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Abdul-Hammed M, Adedotun IO, Falade VA, Adepoju AJ, Olasupo SB, Akinboade MW. Target-based drug discovery, ADMET profiling and bioactivity studies of antibiotics as potential inhibitors of SARS-CoV-2 main protease (M pro). Virusdisease 2021; 32:642-656. [PMID: 34226871 PMCID: PMC8246438 DOI: 10.1007/s13337-021-00717-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/15/2021] [Indexed: 12/24/2022] Open
Abstract
A recent outbreak of a new strain of Coronavirus (SARS-CoV-2) has become a global health burden, which has resulted in deaths. No proven drug has been found to effectively cure this fast-spreading infection, hence the need to explore old drugs with the known profile in tackling this pandemic. A computer-aided drug design approach involving virtual screening was used to obtain the binding scores and inhibiting efficiencies of previously known antibiotics against SARS-CoV-2 main protease (Mpro). The drug-likeness analysis of the repurposed drugs were done using the Molinspiration chemoinformatics tool, while the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis was carried out using ADMET SAR-2 webserver. Other analyses performed include bioactivities of the repurposed drug as a probable anti-SARS-CoV-2 agent and oral bioavailability analyses among others. The results were compared with those of drugs currently involved in clinical trials in the ongoing pandemic. Although antibiotics have been speculated to be of no use in the treatment of viral infections, literature has emerged lately to reveal the antiviral potential and immune-boosting ability of antibiotics. This study identified Tarivid and Ciprofloxacin with binding affinities of - 8.3 kcal/mol and - 8.1 kcal/mol, respectively as significant inhibitors of SARS-CoV-2 (Mpro) with better pharmacokinetics, drug-likeness and oral bioavailability, bioactivity properties, ADMET properties and inhibitory strength compared to Remdesivir (- 7.6 kcal/mol) and Azithromycin (- 6.3 kcal/mol). These observations will provide insight for further research (clinical trial) in the cure and management of COVID-19.
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Affiliation(s)
- Misbaudeen Abdul-Hammed
- Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso, Nigeria
| | - Ibrahim Olaide Adedotun
- Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso, Nigeria
| | - Victoria Adeola Falade
- Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso, Nigeria
| | - Adewusi John Adepoju
- Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso, Nigeria
| | | | - Modinat Wuraola Akinboade
- Department of Biochemistry, Ladoke Akintola University of Technology, P.M.B. 4000, Ogbomoso, Nigeria
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28
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Douglas M, Moy S, Hernandez N. Impact of COVID-19 on Outpatient Antimicrobial Prescribing Patterns in New York City. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2021; 29:e352-e355. [PMID: 34803343 PMCID: PMC8594385 DOI: 10.1097/ipc.0000000000001071] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Antibiotic and antiviral agents may be prescribed in patients with suspected or confirmed coronavirus disease 2019 (COVID-19) infections because of in vitro evidence of cessation of viral replication, potential bacterial secondary or coinfection, and inability to distinguish COVID-19 infections from common bacterial infections. The objective of this study was to evaluate antimicrobial prescribing patterns in the outpatient setting during the initial peak of COVID-19 in New York City. METHODS This single-center, retrospective chart review included patients at least 18 years old who were prescribed oral antimicrobial agents in outpatient primary care clinics between March and May 2020. Data were compared with prescribing patterns from March to May 2019. The primary outcome was the number of antimicrobial prescriptions per 1000 patient visits. Secondary outcomes included documented indication, incidence of confirmed infections, mortality, and/or hospital admission within 90 days. Descriptive statistics were used. RESULTS The overall antimicrobial prescribing rate increased from 31.94 prescriptions per 1000 visits in 2019 to 57.48 prescriptions per 1000 visits in 2020. Agents that were more commonly prescribed during the initial peak of COVID-19 include cefpodoxime, hydroxychloroquine, doxycycline, and sulfamethoxazole-trimethoprim. COVID-19 represented 7 (6%) documented antimicrobial indications in 2020, with agents such as azithromycin, hydroxychloroquine, doxycycline, cefpodoxime, and oseltamivir prescribed. CONCLUSIONS Overall antimicrobial prescribing rates in outpatient primary care clinics increased during the first peak of COVID-19 in an area with high infection burden. This increase may have been influenced by restricted patient evaluation, changes in patient management, and a decrease in overall patient visits.
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Affiliation(s)
| | - Stanley Moy
- SUNY Downstate Health Sciences University, Brooklyn, NY
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29
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Prieto Santamaría L, Díaz Uzquiano M, Ugarte Carro E, Ortiz-Roldán N, Pérez Gallardo Y, Rodríguez-González A. Integrating heterogeneous data to facilitate COVID-19 drug repurposing. Drug Discov Today 2021; 27:558-566. [PMID: 34666181 PMCID: PMC8520166 DOI: 10.1016/j.drudis.2021.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/28/2021] [Accepted: 10/08/2021] [Indexed: 01/03/2023]
Abstract
In the COVID-19 pandemic, drug repositioning has presented itself as an alternative to the time-consuming process of generating new drugs. This review describes a drug repurposing process that is based on a new data-driven approach: we put forward five information paths that associate COVID-19-related genes and COVID-19 symptoms with drugs that directly target these gene products, that target the symptoms or that treat diseases that are symptomatically or genetically similar to COVID-19. The intersection of the five information paths results in a list of 13 drugs that we suggest as potential candidates against COVID-19. In addition, we have found information in published studies and in clinical trials that support the therapeutic potential of the drugs in our final list.
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Affiliation(s)
- Lucía Prieto Santamaría
- ETS Ingenieros Informáticos, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain; Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain; Ezeris Networks Global Services S.L., 28028 Madrid, Spain
| | - Marina Díaz Uzquiano
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain
| | - Esther Ugarte Carro
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain
| | - Nieves Ortiz-Roldán
- Facultativo Especialista Área (FEA), Anestesiología y Reanimación, Hospital Sierrallana, Servicio Cántabro de Salud, 39300 Torrelavega, Cantabria, Spain
| | | | - Alejandro Rodríguez-González
- ETS Ingenieros Informáticos, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain; Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28660 Boadilla del Monte, Madrid, Spain.
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Vitrone M, Mele F, Durante-Mangoni E, Zampino R. Drugs and liver injury: a not to be overlooked binomial in COVID-19. J Chemother 2021; 34:207-220. [PMID: 34644236 DOI: 10.1080/1120009x.2021.1988203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
SARS-CoV-2 infection (COVID-19) results predominantly in pulmonary involvement but a direct, virus-induced liver damage may also occur, whose mechanisms are being actively investigated. Accordingly, it appears of utmost importance to monitor liver function and carefully evaluate hepatic safety of the various drugs administered during COVID-19. In this respect, many drugs, biological agents and novel molecules, whose efficacy in COVID-19 is under scrutiny, have also been shown to potentially cause or worsen liver damage. In this article, we review safety data of established as well as promising agents for COVID-19.
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Affiliation(s)
- M Vitrone
- Department of Advanced Medical & Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - F Mele
- Department of Advanced Medical & Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - E Durante-Mangoni
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli - Monaldi Hospital, Naples, Italy
| | - R Zampino
- Department of Advanced Medical & Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy.,Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli - Monaldi Hospital, Naples, Italy
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31
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Dorobisz K, Dorobisz T, Janczak D, Zatoński T. Doxycycline in the Coronavirus Disease 2019 Therapy. Ther Clin Risk Manag 2021; 17:1023-1026. [PMID: 34584416 PMCID: PMC8464303 DOI: 10.2147/tcrm.s314923] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 06/21/2021] [Indexed: 12/26/2022] Open
Abstract
Acute respiratory syndrome, associated with coronavirus 2 (SARS-CoV-2), is the most important medical and epidemic problem of today. The biggest challenge is to find an effective treatment and to reduce the need for hospitalisation. In the article, the patients with mild to moderate coronavirus disease 2019 (COVID-19) treated with doxycycline with significant improvement have been discussed. Doxycycline is a known antibiotic, but also an anti-inflammatory and immunomodulatory drug, so it seems to be ideal for the treatment of COVID-19. Doxycycline, as an easily available and low-cost medication, should be considered as a COVID-19 therapy in all patients in the first days of the symptoms of a SARS-CoV-2 infection. Due to its immunomodulatory, anti-inflammatory, cardioprotective and antiviral effects, it seems to be an ideal drug for patients with mild, moderate and severe disease. A large multicentre study is needed to evaluate the effects of this medication.
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Affiliation(s)
- Karolina Dorobisz
- Department of Otolaryngology, Head and Neck Surgery, Wroclaw Medical University, Wroclaw, Poland
| | - Tadeusz Dorobisz
- Department of Vascular Surgery, Wroclaw Medical University, Wroclaw, Poland
| | - Dariusz Janczak
- Department of Vascular Surgery, Wroclaw Medical University, Wroclaw, Poland
| | - Tomasz Zatoński
- Department of Otolaryngology, Head and Neck Surgery, Wroclaw Medical University, Wroclaw, Poland
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Soares KO, Oliveira CJBD, Rodrigues AE, Vasconcelos PC, Silva NMVD, Cunha Filho OGD, Madden C, Hale VL. Tetracycline Exposure Alters Key Gut Microbiota in Africanized Honey Bees (Apis mellifera scutellata x spp.). Front Ecol Evol 2021. [DOI: 10.3389/fevo.2021.716660] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Honey bees play a critical role in ecosystem health, biodiversity maintenance, and crop yield. Antimicrobials, such as tetracyclines, are used widely in agriculture, medicine, and in bee keeping, and bees can be directly or indirectly exposed to tetracycline residues in the environment. In European honey bees, tetracycline exposure has been linked with shifts in the gut microbiota that negatively impact bee health. However, the effects of antimicrobials on Africanized honey bee gut microbiota have not been examined. The aim of this study was to investigate the effects of tetracycline exposure on the gut microbial community of Africanized honey bees (Apis mellifera scutellata x spp.), which are important pollinators in South, Central, and North America. Bees (n = 1,000) were collected from hives in Areia-PB, Northeastern Brazil, placed into plastic chambers and kept under controlled temperature and humidity conditions. The control group (CON) was fed daily with syrup (10 g) consisting of a 1:1 solution of demerara sugar and water, plus a solid protein diet (10 g) composed of 60% soy extract and 40% sugar syrup. The tetracycline group (TET) was fed identically but with the addition of tetracycline hydrochloride (450 μg/g) to the sugar syrup. Bees were sampled from each group before (day 0), and after tetracycline exposure (days 3, 6, and 9). Abdominal contents dissected out of each bee underwent DNA extraction and 16S rRNA sequencing (V3-V4) on an Illumina MiSeq. Sequences were filtered and processed through QIIME2 and DADA2. Microbial community composition and diversity and differentially abundant taxa were evaluated by treatment and time. Bee gut microbial composition (Jaccard) and diversity (Shannon) differed significantly and increasingly over time and between CON and TET groups. Tetracycline exposure was associated with decreased relative abundances of Bombella and Fructobacillus, along with decreases in key core microbiota such as Snodgrassella, Gilliamella, Rhizobiaceae, and Apibacter. These microbes are critical for nutrient metabolism and pathogen defense, and it is possible that decreased abundances of these microbes could negatively affect bee health. Considering the global ecological and economic importance of honey bees as pollinators, it is critical to understand the effects of agrochemicals including antimicrobials on honey bees.
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Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity. Viruses 2021; 13:v13091745. [PMID: 34578326 PMCID: PMC8473150 DOI: 10.3390/v13091745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 08/27/2021] [Accepted: 08/28/2021] [Indexed: 12/20/2022] Open
Abstract
The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.
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34
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Miethke M, Pieroni M, Weber T, Brönstrup M, Hammann P, Halby L, Arimondo PB, Glaser P, Aigle B, Bode HB, Moreira R, Li Y, Luzhetskyy A, Medema MH, Pernodet JL, Stadler M, Tormo JR, Genilloud O, Truman AW, Weissman KJ, Takano E, Sabatini S, Stegmann E, Brötz-Oesterhelt H, Wohlleben W, Seemann M, Empting M, Hirsch AKH, Loretz B, Lehr CM, Titz A, Herrmann J, Jaeger T, Alt S, Hesterkamp T, Winterhalter M, Schiefer A, Pfarr K, Hoerauf A, Graz H, Graz M, Lindvall M, Ramurthy S, Karlén A, van Dongen M, Petkovic H, Keller A, Peyrane F, Donadio S, Fraisse L, Piddock LJV, Gilbert IH, Moser HE, Müller R. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem 2021; 5:726-749. [PMID: 34426795 PMCID: PMC8374425 DOI: 10.1038/s41570-021-00313-1] [Citation(s) in RCA: 564] [Impact Index Per Article: 141.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/01/2021] [Indexed: 02/08/2023]
Abstract
An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
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Affiliation(s)
- Marcus Miethke
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | - Marco Pieroni
- Food and Drug Department, University of Parma, Parma, Italy
| | - Tilmann Weber
- The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark
| | - Mark Brönstrup
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Department of Chemical Biology (CBIO), Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | - Peter Hammann
- Infectious Diseases & Natural Product Research at EVOTEC, and Justus Liebig University Giessen, Giessen, Germany
| | - Ludovic Halby
- Epigenetic Chemical Biology, Department of Structural Biology and Chemistry, Institut Pasteur, UMR n°3523, CNRS, Paris, France
| | - Paola B. Arimondo
- Epigenetic Chemical Biology, Department of Structural Biology and Chemistry, Institut Pasteur, UMR n°3523, CNRS, Paris, France
| | - Philippe Glaser
- Ecology and Evolution of Antibiotic Resistance Unit, Microbiology Department, Institut Pasteur, CNRS UMR3525, Paris, France
| | | | - Helge B. Bode
- Department of Biosciences, Goethe University Frankfurt, Frankfurt, Germany
- Max Planck Institute for Terrestrial Microbiology, Department of Natural Products in Organismic Interactions, Marburg, Germany
| | - Rui Moreira
- Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
| | - Yanyan Li
- Unit MCAM, CNRS, National Museum of Natural History (MNHN), Paris, France
| | - Andriy Luzhetskyy
- Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany
| | - Marnix H. Medema
- Bioinformatics Group, Wageningen University and Research, Wageningen, Netherlands
| | - Jean-Luc Pernodet
- Institute for Integrative Biology of the Cell (I2BC) & Microbiology Department, University of Paris-Saclay, Gif-sur-Yvette, France
| | - Marc Stadler
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Microbial Drugs (MWIS), Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | | | | | - Andrew W. Truman
- Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom
| | - Kira J. Weissman
- Molecular and Structural Enzymology Group, Université de Lorraine, CNRS, IMoPA, Nancy, France
| | - Eriko Takano
- Manchester Institute of Biotechnology, Department of Chemistry, School of Natural Sciences, Faculty of Science and Engineering, University of Manchester, Manchester, United Kingdom
| | - Stefano Sabatini
- Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
| | - Evi Stegmann
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Heike Brötz-Oesterhelt
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Wolfgang Wohlleben
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Department of Microbiology/Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Myriam Seemann
- Institute for Chemistry UMR 7177, University of Strasbourg/CNRS, ITI InnoVec, Strasbourg, France
| | - Martin Empting
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | - Anna K. H. Hirsch
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | - Brigitta Loretz
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
| | - Claus-Michael Lehr
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
| | - Alexander Titz
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | - Jennifer Herrmann
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | - Timo Jaeger
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | - Silke Alt
- German Center for Infection Research (DZIF), Braunschweig, Germany
| | | | | | - Andrea Schiefer
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
| | - Kenneth Pfarr
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
| | - Achim Hoerauf
- German Center for Infection Research (DZIF), Braunschweig, Germany
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
| | - Heather Graz
- Biophys Ltd., Usk, Monmouthshire, United Kingdom
| | - Michael Graz
- School of Law, University of Bristol, Bristol, United Kingdom
| | | | | | - Anders Karlén
- Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
| | | | - Hrvoje Petkovic
- Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Andreas Keller
- Chair for Clinical Bioinformatics, Saarland University, University Hospital, Saarbrücken, Germany
| | | | | | - Laurent Fraisse
- Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland
| | - Laura J. V. Piddock
- The Global Antibiotic Research and Development Partnership (GARDP), Geneva, Switzerland
| | - Ian H. Gilbert
- Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, United Kingdom
| | - Heinz E. Moser
- Novartis Institutes for BioMedical Research (NIBR), Emeryville, CA USA
| | - Rolf Müller
- Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), and Department of Pharmacy, Saarland University Campus E8.1, Saarbrücken, Germany
- German Center for Infection Research (DZIF), Braunschweig, Germany
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Sivandzadeh GR, Askari H, Safarpour AR, Ejtehadi F, Raeis-Abdollahi E, Vaez Lari A, Abazari MF, Tarkesh F, Bagheri Lankarani K. COVID-19 infection and liver injury: Clinical features, biomarkers, potential mechanisms, treatment, and management challenges. World J Clin Cases 2021; 9:6178-6200. [PMID: 34434987 PMCID: PMC8362548 DOI: 10.12998/wjcc.v9.i22.6178] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/07/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
It is hypothesized that liver impairment caused by coronavirus disease 2019 (COVID-19) infection might play a central role in severe clinical presentations. Liver injury is closely associated with severe disease and, even with antiviral drugs, have a poor prognosis in COVID-19 patients. In addition to the common hepatobiliary disorders caused by COVID-19, patients with pre-existing liver diseases demand special considerations during the current pandemic. Thus, it is vital that upon clinical presentation, patients with concurrent pre-existing liver disease associated with metabolic dysfunction and COVID-19 be managed properly to prevent liver failure. Careful monitoring and early detection of liver damage through biomarkers after hospitalization for COVID-19 is underscored in all cases, particularly in those with pre-existing metabolic liver injury. The purpose of this study was to determine most recent evidence regarding causality, potential risk factors, and challenges, therapeutic options, and management of COVID-19 infection in vulnerable patients with pre-existing liver injury. This review aims to highlight the current frontier of COVID-19 infection and liver injury and the direction of liver injury in these patients.
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Affiliation(s)
- Gholam Reza Sivandzadeh
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Hassan Askari
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Ali Reza Safarpour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Fardad Ejtehadi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Ehsan Raeis-Abdollahi
- Department of Medical Sciences, Qom Medical Branch, Islamic Azad University, Qom 1417613151, Iran
| | - Armaghan Vaez Lari
- Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz 6135715794, Iran
| | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran 1417653761, Iran
| | - Firoozeh Tarkesh
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
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Tazikeh-Lemeski E, Moradi S, Raoufi R, Shahlaei M, Janlou MAM, Zolghadri S. Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study. J Biomol Struct Dyn 2021; 39:4633-4646. [PMID: 32573355 PMCID: PMC7332864 DOI: 10.1080/07391102.2020.1779133] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 06/02/2020] [Indexed: 01/17/2023]
Abstract
Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shape-based screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
| | - Sajad Moradi
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Rahim Raoufi
- School of Medicine, Jahrom University of Medical Science, Jahrom, Iran
| | - Mohsen Shahlaei
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Samaneh Zolghadri
- Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
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37
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Mortaz E, Bezemer G, Alipoor SD, Varahram M, Mumby S, Folkerts G, Garssen J, Adcock IM. Nutritional Impact and Its Potential Consequences on COVID-19 Severity. Front Nutr 2021; 8:698617. [PMID: 34291074 PMCID: PMC8287001 DOI: 10.3389/fnut.2021.698617] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 05/24/2021] [Indexed: 12/24/2022] Open
Abstract
Background: During late 2019 a viral disease due to a novel coronavirus was reported in Wuhan, China, which rapidly developed into an exploding pandemic and poses a severe threat to human health all over the world. Until now (May 2021), there are insufficient treatment options for the management of this global disease and shortage of vaccines. Important aspects that help to defeat coronavirus infection seems to be having a healthy, strong, and resilient immune system. Nutrition and metabolic disorders, such as obesity and diabetes play a crucial role on the community health situation in general and especially during this new pandemic. There seems to be an enormous impact of lifestyle, metabolic disorders, and immune status on coronavirus disease 2019 (COVID-19) severity and recovery. For this reason, it is important to consider the impact of lifestyle and the consumption of well-defined healthy diets during the pandemic. Aims: In this review, we summarise recent findings on the effect of nutrition on COVID-19 susceptibility and disease severity and treatment. Understanding how specific dietary features might help to improve the public health strategies to reduce the rate and severity of COVID-19.
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Affiliation(s)
- Esmaeil Mortaz
- Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Clinical Tuberculosis and Epidemiology Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gillina Bezemer
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
- Impact Station, Hilversum, Netherlands
| | - Shamila D. Alipoor
- Molecular Medicine Department, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Mohammad Varahram
- Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sharon Mumby
- Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Gert Folkerts
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
- Center of Excellence Immunology, Nutricia Research, Utrecht, Netherlands
| | - Ian M. Adcock
- Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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GERÇEK Z, CEYHAN D, ERÇAĞ E. Synthesis and molecular docking study of novel COVID-19 inhibitors. Turk J Chem 2021; 45:704-718. [PMID: 34385863 PMCID: PMC8326476 DOI: 10.3906/kim-2012-55] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 03/04/2021] [Indexed: 09/23/2023] Open
Abstract
In 2020, the world tried to combat the corona virus (COVID-19) pandemic. A proven treatment method specific to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is still not found. In this study, seven new antiviral compounds were designed for COVID-19 treatment. The ability of these compounds to inhibit COVID-19's RNA processing was calculated by the molecular docking study. It has been observed that the compounds can have high binding affinities especially against NSP12 (between -9.06 and -8.00 kcal/mol). The molecular dynamics simulation of NSP12-ZG 7 complex proved the stability of interaction. The synthesis of two most active molecules was performed by one-pot reaction and characterized by FT-IR, 1H-NMR, 13C-NMR, and mass spectroscopy. The compounds presented with their synthesis are inhibitory core structures against SARS-CoV-2 infection.
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Affiliation(s)
- Zuhal GERÇEK
- Department of Chemistry, Faculty of Arts and Sciences, Bülent Ecevit University, ZonguldakTurkey
| | - Deniz CEYHAN
- Department of Chemistry, Faculty of Art and Science, Tekirdağ Namık Kemal University, TekirdağTurkey
| | - Erol ERÇAĞ
- Department of Chemistry, Faculty of Art and Science, Tekirdağ Namık Kemal University, TekirdağTurkey
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39
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YAYLI N, KILIÇ G, ÇELİK G, KAHRİMAN N, KANBOLAT Ş, BOZDEVECİ A, ALPAY KARAOĞLU Ş, ALİYAZICIOĞLU R, SELLİTEPE HE, DOĞAN İS, AYDIN A. Synthesis of hydroxy benzoin/benzil analogs and investigation of their antioxidant, antimicrobial, enzyme inhibition, and cytotoxic activities. Turk J Chem 2021; 45:788-804. [PMID: 37635901 PMCID: PMC10454678 DOI: 10.3906/kim-2012-25] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 03/22/2021] [Indexed: 01/18/2023] Open
Abstract
In this study, hydroxy benzoin ( 1-7 ), benzil ( 8-14 ), and benzoin/benzil-O-β-D-glucosides ( 15-25 ) were synthesized to investigate their biological activities. An efficient method for synthesizing hydroxy benzoin compounds ( 1 - 7 ) was prepared from four different benzaldehydes using an ultrasonic bath. Then, antioxidant (FRAP, CUPRAC, and DPPH), antimicrobial (3 Gram (-), 4/6 Gram (+), one tuberculosis and one fungus), and enzyme inhibition (acetylcholinesterase, butyrylcholine esterase, tyrosinase, α-amylase, and α- glucosidase) for the all synthesized compounds ( 1-25 ) were evaluated. And also, four most active compounds ( 4 , 12 , 18a+b , and 25 ) from each group were evaluated to the human cervical cancer cell line (HeLa) and anticancer screening tests against the human retinal normal cell line (RPE). Compound 4 showed HeLa and RPE cancer cell activities as much as cisplatin. The synthesized compounds were characterized by spectroscopic methods (NMR, FT-IR, UV, LC-QTOF-MS) and the ACD NMR program's help.
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Affiliation(s)
- Nurettin YAYLI
- Department of Pharmacognosy, Faculty of Pharmacy, Karadeniz Technical University, TrabzonTurkey
| | - Gözde KILIÇ
- Department of Pharmacognosy, Faculty of Pharmacy, Karadeniz Technical University, TrabzonTurkey
| | - Gonca ÇELİK
- Department of Chemistry, Faculty of Science, Karadeniz Technical University, TrabzonTurkey
| | - Nuran KAHRİMAN
- Department of Chemistry, Faculty of Science, Karadeniz Technical University, TrabzonTurkey
| | - Şeyda KANBOLAT
- Department of Biochemistry, Faculty of Pharmacy, Karadeniz Technical University, TrabzonTurkey
| | - Arif BOZDEVECİ
- Department of Biology, Faculty of Arts and Science, Recep Tayyip Erdoğan University, RizeTurkey
| | - Şengül ALPAY KARAOĞLU
- Department of Biology, Faculty of Arts and Science, Recep Tayyip Erdoğan University, RizeTurkey
| | - Rezzan ALİYAZICIOĞLU
- Department of Biochemistry, Faculty of Pharmacy, Karadeniz Technical University, TrabzonTurkey
| | - Hasan Erdinç SELLİTEPE
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Karadeniz Technical University, TrabzonTurkey
| | - İnci Selin DOĞAN
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Karadeniz Technical University, TrabzonTurkey
| | - Ali AYDIN
- Department of Medical Biology, Faculty of Medicine, Yozgat Bozok University, YozgatTurkey
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Alam S, Kamal TB, Sarker MMR, Zhou JR, Rahman SMA, Mohamed IN. Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021. Front Pharmacol 2021; 12:659577. [PMID: 34220503 PMCID: PMC8243370 DOI: 10.3389/fphar.2021.659577] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.
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Affiliation(s)
- Safaet Alam
- Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh
| | | | - Md. Moklesur Rahman Sarker
- Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh
- Pharmacology and Toxicology Research Division, Health Med Science Research Limited, Dhaka, Bangladesh
| | - Jin-Rong Zhou
- Nutrition/Metabolism Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - S. M. Abdur Rahman
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Isa Naina Mohamed
- Pharmacology Department, Medical Faculty, Universiti Kebangsaan Malaysia (The National University of Malaysia), Kuala Lumpur, Malaysia
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Alexander PE, Armstrong R, Fareed G, Lotus J, Oskoui R, Prodromos C, Risch HA, Tenenbaum HC, Wax CM, Dara P, McCullough PA, Gill KK. Early multidrug treatment of SARS-CoV-2 infection (COVID-19) and reduced mortality among nursing home (or outpatient/ambulatory) residents. Med Hypotheses 2021; 153:110622. [PMID: 34130113 PMCID: PMC8178530 DOI: 10.1016/j.mehy.2021.110622] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 05/25/2021] [Accepted: 06/02/2021] [Indexed: 12/18/2022]
Abstract
The outbreak of COVID-19 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world with tremendous morbidity and mortality in the elderly. In-hospital treatment addresses the multifaceted nature of the illness including initial viral replication, cytokine storm, and endothelial injury with thrombosis. We identified nine reports of early treatment outcomes in COVID-19 nursing home patients. Multi-drug therapy including hydroxychloroquine with one or more anti-infectives, corticosteroids, and antithrombotic anti-blood clotting agents can be extended to seniors in the nursing home setting without hospitalization. Data from nine studies found hydroxychloroquine-based multidrug regimens were associated with a statistically significant > 60% reduction in mortality. Going forward, we conclude that early empiric treatment for the elderly with COVID-19 in the nursing home setting (or similar congregated settings with elderly residents/patients e.g. LTF or ALF) has a reasonable probability of success and acceptable safety. This group remains our highest at-risk group and warrants acute treatment focus prior to symptoms worsening. Given the rapidity and severity of SARS-CoV-2 outbreaks in nursing homes, in-center treatment of acute COVID-19 patients is a reasonable strategy to reduce the risks of hospitalization and death. If elderly high-risk patients in such congregated nursing home type settings are allowed to worsen with no early treatment, they may be too sick and fragile to benefit from in-hospital therapeutics and are at risk for pulmonary failure, life-ending micro-thrombi of the lungs, kidneys etc. The issue is timing of therapeutics, and we argue that early treatment before hospitalization, is the right time and can potentially save lives, especially among our higher-risk elderly populations hit hardest by severe illness and death from COVID-19. We must reiterate, we are talking about ‘early’ treatment before the disease is far along in the disease sequelae where the patient then needs hospitalization and aggressive interventions. We are referring to the initial days e.g. day one, post infection when symptoms emerge or there is strong clinical suspicion. This early therapeutic option deserves serious and urgent consideration by the medical establishment and respective decision-makers. Doctors must be allowed their clinical discretion in how they optimally treat their patients. Doctors must be brave and trust their skilled judgements and do all to save the lives of their patients. We therefore hypothesize that early outpatient ambulatory treatment, once initiated as soon as symptoms begin in high-risk positive persons, would significantly reduce hospitalizations and prevent deaths. Specifically, the provision of early multi-drug sequenced therapy with repurposed drugs will reduce hospitalization and death in elderly patients being cared for in long-term-care facilities. The most important implications of our hypothesis are: 1) hospitalizations and deaths would be reduced 2) transmission would be reduced due to the mitigation of symptoms and 3) recovery following infection and treatment provides for natural exposure immunity that is broad based, durable, and robust (helping towards natural immunity within the population). The end result is reduced strain on hospitals and systems that would allow for other non-COVID illnesses to receive care.
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Affiliation(s)
- Paul E Alexander
- McMaster University and GUIDE Research Methods Group, Hamilton, Ontario, Canada.
| | | | | | - John Lotus
- The Foundation for Orthopaedics and Regenerative Medicine (FOReM), Chicago, IL, USA.
| | - Ramin Oskoui
- CEO, Foxhall Cardiology, PC, Washington, DC, USA
| | - Chad Prodromos
- The Foundation for Orthopaedics and Regenerative Medicine (FOReM), Chicago, IL, USA
| | | | - Howard C Tenenbaum
- Centre for Advanced Dental Research and Care, Mount Sinai Hospital, and Faculties of Medicine and Dentistry, University of Toronto, Toronto, ON, Canada.
| | - Craig M Wax
- Family Physician, Independent Physicians for Patient Independence, AAPS Board of Directors, NJ, USA.
| | - Parvez Dara
- Consultant, Medical Hematologist and Oncologist, USA
| | - Peter A McCullough
- Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX, USA.
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Yacouba A, Olowo-Okere A, Yunusa I. Repurposing of antibiotics for clinical management of COVID-19: a narrative review. Ann Clin Microbiol Antimicrob 2021; 20:37. [PMID: 34020659 PMCID: PMC8139224 DOI: 10.1186/s12941-021-00444-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 05/11/2021] [Indexed: 12/22/2022] Open
Abstract
Background Drug repurposing otherwise known as drug repositioning or drug re-profiling is a time-tested approach in drug discovery through which new medical uses are being established for already known drugs. Antibiotics are among the pharmacological agents being investigated for potential anti-SARS-COV-2 activities. The antibiotics are used either to resolve bacterial infections co-existing with COVID-19 infections or exploitation of their potential antiviral activities. Herein, we aimed to review the various antibiotics that have been repositioned for the management of COVID-19. Methods This literature review was conducted from a methodical search on PubMed and Web of Science regarding antibiotics used in patients with COVID-19 up to July 5, 2020. Results Macrolide and specifically azithromycin is the most common antibiotic used in the clinical management of COVID-19. The other antibiotics used in COVID-19 includes teicoplanin, clarithromycin, doxycycline, tetracyclines, levofloxacin, moxifloxacin, ciprofloxacin, and cefuroxime. In patients with COVID-19, antibiotics are used for their immune-modulating, anti-inflammatory, and antiviral properties. The precise antiviral mechanism of most of these antibiotics has not been determined. Moreover, the use of some of these antibiotics against SARS-CoV-2 infection remains highly controversial and not widely accepted. Conclusion The heavy use of antibiotics during the COVID-19 pandemic would likely worsen antibiotic resistance crisis. Consequently, antibiotic stewardship should be strengthened in order to prevent the impacts of COVID-19 on the antibiotic resistance crisis.
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Affiliation(s)
- Abdourahamane Yacouba
- Faculté des Sciences de la Santé, Université Abdou Moumouni, P.M.B. 10896, Niamey, Niger.
| | - Ahmed Olowo-Okere
- Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Ismaeel Yunusa
- Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC, USA
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Mahmud R, Rahman MM, Alam I, Ahmed KGU, Kabir AH, Sayeed SJB, Rassel MA, Monayem FB, Islam MS, Islam MM, Barshan AD, Hoque MM, Mallik MDU, Yusuf MA, Hossain MZ. Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial. J Int Med Res 2021; 49:3000605211013550. [PMID: 33983065 PMCID: PMC8127799 DOI: 10.1177/03000605211013550] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 04/06/2021] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE We evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection. METHODS This was a randomized, blinded, placebo-controlled trial in patients with mild-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR. RESULTS Among 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4-10, treatment group) and 9 (5-12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60-0.90). The number of patients with a ≤7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04-0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group. CONCLUSIONS Patients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04523831. DATA REPOSITORY ID Dryad. doi:10.5061/dryad.qjq2bvqf6.
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Affiliation(s)
- Reaz Mahmud
- Department of Neurology, Dhaka Medical College, Dhaka, Bangladesh
| | - Md. Mujibur Rahman
- Department of Medicine, Dhaka Medical College Hospital, Dhaka, Bangladesh
| | - Iftikher Alam
- Department of Neurology, Dhaka Medical College, Dhaka, Bangladesh
| | | | | | | | | | | | | | | | | | | | - MD. Uzzal Mallik
- Department of Medicine, Dhaka Medical College Hospital, Dhaka, Bangladesh
| | - Mohammad Abdullah Yusuf
- Department of Microbiology, National Institute of Neurosciences and Hospital, Dhaka, Bangladesh
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Yim J, Lim HH, Kwon Y. COVID-19 and pulmonary fibrosis: therapeutics in clinical trials, repurposing, and potential development. Arch Pharm Res 2021; 44:499-513. [PMID: 34047940 PMCID: PMC8161353 DOI: 10.1007/s12272-021-01331-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 05/04/2021] [Indexed: 02/07/2023]
Abstract
In 2019, an unprecedented disease named coronavirus disease 2019 (COVID-19) emerged and spread across the globe. Although the rapid transmission of COVID-19 has resulted in thousands of deaths and severe lung damage, conclusive treatment is not available. However, three COVID-19 vaccines have been authorized, and two more will be approved soon, according to a World Health Organization report on December 12, 2020. Many COVID-19 patients show symptoms of acute lung injury that eventually leads to pulmonary fibrosis. Our aim in this article is to present the relationship between pulmonary fibrosis and COVID-19, with a focus on angiotensin converting enzyme-2. We also evaluate the radiological imaging methods computed tomography (CT) and chest X-ray (CXR) for visualization of patient lung condition. Moreover, we review possible therapeutics for COVID-19 using four categories: treatments related and unrelated to lung disease and treatments that have and have not entered clinical trials. Although many treatments have started clinical trials, they have some drawbacks, such as short-term and small-group testing, that need to be addressed as soon as possible.
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Affiliation(s)
- Joowon Yim
- College of Pharmacy, Ewha Womans University, 120-750, Seoul, Republic of Korea
| | - Hee Hyun Lim
- College of Pharmacy, Ewha Womans University, 120-750, Seoul, Republic of Korea
| | - Youngjoo Kwon
- College of Pharmacy, Ewha Womans University, 120-750, Seoul, Republic of Korea.
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Al-kuraishy HM, Al-Gareeb AI, Alqarni M, Cruz-Martins N, El-Saber Batiha G. Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives. Front Pharmacol 2021; 12:642822. [PMID: 33967777 PMCID: PMC8103613 DOI: 10.3389/fphar.2021.642822] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 01/18/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 15% of severe cases require an intensive care unit (ICU) admission and mechanical ventilation due to development of acute respiratory distress syndrome (ARDS). Tetracyclines (TCs) are a group of bacteriostatic antibiotics, like tetracycline, minocycline, and doxycycline, effective against aerobic and anaerobic bacteria as well as Gram-positive and Gram-negative bacteria. Based on available evidences, TCs may be effective against coronaviruses and thus useful to treat COVID-19. Thus, this review aims to provide a brief overview on the uses of TCs for COVID-19 management. SARS-CoV-2 and other coronaviruses depend mainly on the matrix metalloproteinases (MMPs) for their proliferation, cell adhesion, and infiltration. The anti-inflammatory mechanisms of TCs are linked to different pathways. Briefly, TCs inhibit mitochondrial cytochrome c and caspase pathway with improvement of lymphopenia in early COVID-19. Specifically, minocycline is effective in reducing COVID-19-related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-α. Different clinical trials recommend the replacement of azithromycin by minocycline in the management of COVID-19 patients at high risk due to two main reasons: 1) minocycline does not prolong the QT interval and even inhibits ischemia-induced arrhythmia; 2) minocycline displays synergistic effect with chloroquine against SARS-CoV-2. Taken together, the data presented here show that TCs, mainly doxycycline or minocycline, may be potential partners in COVID-19 management, derived pneumonia, and related complications, such as acute lung injury (ALI) and ARDS.
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Affiliation(s)
- Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Al-Mustansiriya University, BaghdadIraq
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Al-Mustansiriya University, BaghdadIraq
| | - Mohammed Alqarni
- Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
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Batiha GES, Zayed MA, Awad AA, Shaheen HM, Mustapha S, Herrera-Calderon O, Pagnossa JP, Algammal AM, Zahoor M, Adhikari A, Pandey I, Elazab ST, Rengasamy KRR, Cruz-Martins N, Hetta HF. Management of SARS-CoV-2 Infection: Key Focus in Macrolides Efficacy for COVID-19. Front Med (Lausanne) 2021; 8:642313. [PMID: 33937285 PMCID: PMC8079973 DOI: 10.3389/fmed.2021.642313] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/23/2021] [Indexed: 12/24/2022] Open
Abstract
Macrolides (e.g., erythromycin, fidaxomicin, clarithromycin, and azithromycin) are a class of bacteriostatic antibiotics commonly employed in medicine against various gram-positive and atypical bacterial species mostly related to respiratory tract infections, besides they possess anti-inflammatory and immunomodulatory effects. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). It was first detected in Wuhan, Hubei, China, in December 2019 and resulted in a continuing pandemic. Macrolides have been extensively researched as broad adjunctive therapy for COVID-19 due to its immunostimulant abilities. Among such class of drugs, azithromycin is described as azalide and is well-known for its ability to decrease the production of pro-inflammatory cytokines, including matrix metalloproteinases, tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8. In fact, a report recently published highlighted the effectiveness of combining azithromycin and hydroxychloroquine for COVID-19 treatment. Indeed, it has been underlined that azithromycin quickly prevents SARS-CoV-2 infection by raising the levels of both interferons and interferon-stimulated proteins at the same time which reduces the virus replication and release. In this sense, the current review aims to evaluate the applications of macrolides for the treatment of COVID-19.
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Affiliation(s)
- Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
| | - Marwa A. Zayed
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
| | - Aya A. Awad
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
| | - Hazem M. Shaheen
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
| | - Suleiman Mustapha
- Department of Crop Protection, University of Ilorin, Ilorin, Nigeria
| | - Oscar Herrera-Calderon
- Department of Pharmacology, Bromatology and Toxicology, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | | | - Abdelazeem M. Algammal
- Department of Bacteriology, Immunology, and Mycology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Muhammad Zahoor
- Department of Biochemistry, University of Malakand, Chakdara, Pakistan
| | - Achyut Adhikari
- Central Department of Chemistry, Tribhuwan University, Kritipur, Nepal
| | - Ishan Pandey
- Department of Pathology, Motilal Nehru Medical College, Prayagraj, India
| | - Sara T. Elazab
- Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Kannan R. R. Rengasamy
- Green Biotechnologies Research Centre of Excellence, University of Limpopo, Polokwane, South Africa
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Helal F. Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
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Sayed AM, Khalaf AM, Abdelrahim MEA, Elgendy MO. Repurposing of some anti-infective drugs for COVID-19 treatment: A surveillance study supported by an in silico investigation. Int J Clin Pract 2021; 75:e13877. [PMID: 33300221 PMCID: PMC7883047 DOI: 10.1111/ijcp.13877] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 11/27/2020] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE The repurposing of nitazoxanide, doxycycline and azithromycin may be effective to improve the symptoms in mild and moderate COVID-19 subjects. This study aimed to detect and explain the efficacy of reusing of these drugs in treating COVID-19. METHODS The study was divided into two parts: clinical and computational parts. In the clinical part, 80 (30 females) subjects with reverse transcription-polymerase chain reaction-confirmed COVID-19 with mild and moderate symptoms were enrolled in the study. Subjects were treated with azithromycin or doxycycline, and nitazoxanide was added to the treatment if the subject had diarrhoea. Subjects were divided into four groups: Group 1: subjects treated with azithromycin (20 subjects); Group 2: subjects treated with doxycycline (20 subjects); Group 3: subjects treated with a combination of nitazoxanide and doxycycline (20 subjects); and Group 4: subjects treated with a combination of nitazoxanide and azithromycin (20 subjects). In the computational part, we docked the three drugs against all currently available COVID-19-related protein targets (viral and non-viral). Subsequently, top hits were subjected to molecular dynamic simulations (MDSs) (50 ns) and binding free energy calculations to further validate the docking experiments and to investigate the binding modes of the potential inhibitors. RESULTS The symptomatic improvement of mild to moderate subjects was seen on the fifth day after starting treatment in Group 3 and Group 4 and on the seventh day in Group 2. However, for Group 1, the symptomatic improvement of mild to moderate subjects was not seen on the fifth day and required replacement by doxycycline to get the symptomatic improvement. None of the subjects needed intensive care admission and no deaths were reported. In silico, results were in good accordance with the clinical outcomes, where both nitazoxanide and doxycycline achieved the best docking scores against the viral ADP-ribose phosphatase (ADPRP) and the human Adaptor-Associated Kinase 1 (AAK1). MDSs revealed that both drugs were stable in their bindings indicating that they can be considered as lead molecules for targeting ADPRP and AAK1. CONCLUSION The clinical and computational studies applied on three FDA-approved antimicrobials together with their recent clinical findings revealed that both nitazoxanide and doxycycline have great therapeutic potential against COVID-19. The future in vitro mechanistic investigation may confirm our primary computational outcomes, and in turn, these classes of compounds provide a promising starting point for further anti-COVID-19 therapeutics.
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Affiliation(s)
- Ahmed M. Sayed
- Pharmacognosy DepartmentFaculty of PharmacyNahda UniversityBeni‐SuefEgypt
| | - Ahmed M. Khalaf
- Internal Medicine DepartmentFaculty of MedicineBeni‐Suef UniversityBeni‐SuefEgypt
| | | | - Marwa O. Elgendy
- Clinical Pharmacy DepartmentTeaching Hospital of Faculty of MedicineFaculty of MedicineBeni‐Suef UniversityBeni‐SuefEgypt
- Clinical Pharmacy DepartmentFaculty of PharmacyNahda University (NUB)Egypt
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Al-Kuraishy HM, Al-Gareeb AI, Qusty N, Cruz-Martins N, El-Saber Batiha G. Sequential doxycycline and colchicine combination therapy in Covid-19: The salutary effects. Pulm Pharmacol Ther 2021; 67:102008. [PMID: 33727066 PMCID: PMC7955803 DOI: 10.1016/j.pupt.2021.102008] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 02/08/2023]
Abstract
Coronavirus virus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), actually considered as a global pandemic. The entry-point for SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4), which are highly expressed in the lung. Among other complications, COVID-19leads to fatal pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to development of cytokine storm (CS). The pathogenesis of SARS-CoV-2 infection depends on the viral load and human innate/adaptive immune response that are required for viral elimination in the first phase of COVID-19. However, an exaggerated immune response in the second phase of COVID-19 results in immune overreaction and CS-induced ALI and ARDS. Thus, in view of these considerations, we report here a series of five patients with COVID-19 pneumonia who developed ALI. In addition to the supportive therapy, the patients received doxycycline in the first week and doxycycline plus colchicine in the second week. Following sequential therapy with doxycycline and/or colchicine in patients with COVID-19 pneumonia, the patients had reduction of disease severity and symptoms with better clinical and radiological outcomes. However, it is tough to confirm the link between this therapeutic combination and recovery from COVID-19 pneumonia, as it is a small case-series report. Nevertheless, this study gives a rational for large-scale prospective studies to evaluate the dual sequential effect of doxycycline and colchicine on the COVID-19 severity. This case-series illustrated that use of colchicine: doxycycline combination is linked with marked improvements in the clinical, laboratory and radiological outcomes in patients with COVID-19 pneumonia. However, we cannot sketch any definitive conclusion from our observation, despite we hypothesize that this combination therapeutic regimen may attenuate and treat COVID-19. Further, namely prospective, randomized, and controlled clinical studies are recommended in this regard.
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Affiliation(s)
- Hayder M Al-Kuraishy
- Professor in Department of Clinical Pharmacology and Therapeutic Medicine, College of Medicine, AL-Mustansiriyiah University, Iraq.
| | - Ali I Al-Gareeb
- Professor in Department of Clinical Pharmacology and Therapeutic Medicine, College of Medicine, AL-Mustansiriyiah University, Iraq.
| | - Naeem Qusty
- Medical Laboratories Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia.
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319, Porto, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135, Porto, Portugal; Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Portugal.
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.
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Singh H, Chauhan P, Singh J, Saurabh S, Gautam CS, Kakkar AK. Concomitant use of dexamethasone and tetracyclines: a potential therapeutic option for the management of severe COVID-19 infection? Expert Rev Clin Pharmacol 2021; 14:315-322. [PMID: 33586566 PMCID: PMC7938652 DOI: 10.1080/17512433.2021.1888714] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 02/08/2021] [Indexed: 02/07/2023]
Abstract
Introduction: The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes.Areas covered: Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19.Expert opinion: The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.
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Affiliation(s)
- Harmanjit Singh
- Department of Pharmacology, Government Medical College and Hospital, Chandigarh, India
| | - Prerna Chauhan
- Multidisciplinary Research Unit, Government Medical College and Hospital, Chandigarh, India
| | - Jasbir Singh
- Department of Pharmacology, Government Medical College and Hospital, Chandigarh, India
- Department of Pharmacology, Rajindra Hospital, Patiala, India
| | - Saurabh Saurabh
- Department of Neurosurgery, Dayanand Medical College and Hospital, Ludhiana, India
| | - CS Gautam
- Department of Pharmacology, Government Medical College and Hospital, Chandigarh, India
| | - Ashish Kumar Kakkar
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Zhao TY, Patankar NA. Tetracycline as an inhibitor to the SARS-CoV-2. J Cell Biochem 2021; 122:752-759. [PMID: 33619758 PMCID: PMC8014839 DOI: 10.1002/jcb.29909] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 02/01/2021] [Accepted: 02/03/2021] [Indexed: 01/17/2023]
Abstract
The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an extant threat against public health on a global scale. Cell infection begins when the spike protein of SARS-CoV-2 binds with the human cell receptor, angiotensin-converting enzyme 2 (ACE2). Here, we address the role of tetracycline as an inhibitor for the receptor-binding domain (RBD) of the spike protein. Targeted molecular investigation show that tetracycline binds more favorably to the RBD (-9.40 kcal/mol) compared to doxycycline (-8.08 kcal/mol), chloroquine (-6.31 kcal/mol), or gentamicin (-4.83 kcal/mol) while inhibiting attachment to ACE2 to a greater degree (binding efficiency of 2.98 kcal/(mol nm2 ) for tetracycline-RBD, 5.16 kcal/(mol nm2 ) for doxycycline-RBD, 5.59 kcal/(mol nm2 ) for chloroquine-RBD, and 7.02 kcal/(mol nm2 ) for gentamicin-RBD. Stronger inhibition by tetracycline is verified with nonequilibrium PMF calculations, for which the tetracycline-RBD complex exhibits the lowest free energy profile along the dissociation pathway from ACE2. Tetracycline binds to tyrosine and glycine residues on the viral contact interface that are known to modulate molecular recognition and bonding affinity. These RBD residues also engage in significant hydrogen bonding with the human receptor ACE2. The ability to preclude cell infection complements the anti-inflammatory and cytokine suppressing capability of tetracycline; this may reduce the duration of ICU stays and mechanical ventilation induced by the coronavirus SARS-CoV-2.
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Affiliation(s)
- Tom Y Zhao
- Department of Mechanical Engineering, Northwestern University, Evanston, Illinois, USA
| | - Neelesh A Patankar
- Department of Mechanical Engineering, Northwestern University, Evanston, Illinois, USA
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