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Karan S, Opdensteinen P, Ma Y, De Oliveira JFA, Steinmetz NF. A replicon-based COVID-19 vaccine candidate delivered by tobacco mosaic virus-like particles. Vaccine 2025; 53:127063. [PMID: 40168732 DOI: 10.1016/j.vaccine.2025.127063] [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: 08/21/2024] [Revised: 03/12/2025] [Accepted: 03/20/2025] [Indexed: 04/03/2025]
Abstract
The COVID-19 pandemic highlights the opportunity for mRNA vaccines and their nanotechnology carriers to make an impact as a countermeasure to infectious disease. As alternative to the synthetic lipid nanoparticles or mammalian viruses, we developed a tobacco mosaic virus (TMV)-based mRNA vaccine delivery platform. Specifically, purified coat protein from TMV was used to package a self-amplifying Nodamura replicon expressing the receptor binding domain (RBD) from the Omicron strain of SARS-CoV-2. The replicon construct contains the origin of assembly sequence from the tobacco mosaic virus (TMV) for encapsulation and mRNA stabilization. The nanoparticle vaccine was obtained through in vitro assembly using purified TMV coat proteins and in vitro transcribed mRNA cassettes. Cell assays confirmed delivery of self-amplifying mRNA vaccine, amplification of the transgene and expression of the target protein, RBD, in mammalian cells. Immunization of mice yielded RBD-specific IgG antibodies that demonstrated neutralization of SARS-CoV-2 using an in vitro neutralization assay. The TMV platform nanotechnology does not require ultralow freezers for storage or distribution; and the in vitro assembly method provide 'plug-and-play' to adapt the vaccine formulation rapidly as new strains or diseases emerge. Finally, opportunity exists to produce and self-assemble the vaccine candidate in plants through molecular farming techniques, which may allow production in the region-for the region and could make a contribution to less resourced areas of the world.
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MESH Headings
- Tobacco Mosaic Virus/genetics
- Animals
- COVID-19 Vaccines/immunology
- COVID-19 Vaccines/administration & dosage
- COVID-19 Vaccines/genetics
- Mice
- Replicon
- Antibodies, Viral/immunology
- Antibodies, Viral/blood
- SARS-CoV-2/immunology
- SARS-CoV-2/genetics
- Antibodies, Neutralizing/immunology
- Antibodies, Neutralizing/blood
- COVID-19/prevention & control
- COVID-19/immunology
- Vaccines, Virus-Like Particle/immunology
- Vaccines, Virus-Like Particle/administration & dosage
- Vaccines, Virus-Like Particle/genetics
- Humans
- Vaccines, Synthetic/immunology
- Vaccines, Synthetic/administration & dosage
- Spike Glycoprotein, Coronavirus/immunology
- Spike Glycoprotein, Coronavirus/genetics
- Female
- Capsid Proteins/immunology
- Capsid Proteins/genetics
- Immunoglobulin G/immunology
- Immunoglobulin G/blood
- Mice, Inbred BALB C
- Nanoparticles
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Affiliation(s)
- Sweta Karan
- Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, CA, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, United States
| | - Patrick Opdensteinen
- Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, CA, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, United States
| | - Yifeng Ma
- Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, CA, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, United States
| | - Jessica Fernanda Affonso De Oliveira
- Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, CA, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, United States
| | - Nicole F Steinmetz
- Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, CA, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, CA, United States; Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States; Department of Radiology, University of California, San Diego, La Jolla, CA, United States; Institute for Materials Discovery and Design, University of California, San Diego, La Jolla, CA, United States; Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States; Center for Engineering in Cancer, Institute of Engineering Medicine, University of California, San Diego, La Jolla, CA, United States.
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Oliver JL, Bernaola-Galván P, Carpena P, Perfectti F, Gómez-Martín C, Castiglione S, Raia P, Verdú M, Moya A. Strong evidence for the evolution of decreasing compositional heterogeneity in SARS-CoV-2 genomes during the pandemic. Sci Rep 2025; 15:12246. [PMID: 40210974 PMCID: PMC11985940 DOI: 10.1038/s41598-025-95893-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 03/25/2025] [Indexed: 04/12/2025] Open
Abstract
The rapid evolution of SARS-CoV-2 during the pandemic was characterized by the fixation of a plethora of mutations, many of which enable the virus to evade host resistance, likely altering the virus' genome compositional structure (i.e., the arrangement of compositional domains of varying lengths and nucleotide frequencies within the genome). To explore this hypothesis, we summarize the evolutionary effects of these mutations by computing the Sequence Compositional Complexity (SCC) in random stratified datasets of fully sequenced genomes. Phylogenetic ridge regression of SCC against time reveals a striking downward evolutionary trend, suggesting the ongoing adaptation of the virus's genome structure to the human host. Other genomic features, such as strand asymmetry, the effective number of K-mers, and the depletion of CpG dinucleotides, each linked to the virus's adaptation to its human host, also exhibit decreasing phylogenetic trends throughout the pandemic, along with strong phylogenetic correlations to SCC. We hypothesize that viral CpG depletion (throughout C➔U changes), promoted by directional mutational pressures exerted on the genome by the host antiviral defense systems, may play a key role in the decrease of SARS-CoV-2 genome compositional heterogeneity, with specific adaptation to the human host occurring as a form of genetic mimicry. Overall, our findings suggest a decelerating evolution of reduced compositional complexity in SCC, whereas the number of K-mers and the depletion of CpG dinucleotides are still increasing. These results indicate a genome-wide evolutionary trend toward a more symmetric and homogeneous genome compositional structure in SARS-CoV-2, which is partly still ongoing.
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Affiliation(s)
- José L Oliver
- Department of Genetics, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
- Laboratory of Bioinformatics, Institute of Biotechnology, Center of Biomedical Research, 18100, Granada, Spain.
| | - Pedro Bernaola-Galván
- Department of Applied Physics II and Institute Carlos I for Theoretical and Computational Physics, University of Málaga, Málaga, 29071, Spain
| | - Pedro Carpena
- Department of Applied Physics II and Institute Carlos I for Theoretical and Computational Physics, University of Málaga, Málaga, 29071, Spain
| | - Francisco Perfectti
- Department of Genetics, Faculty of Sciences, University of Granada, 18071, Granada, Spain
- Research Unit Modeling Nature, Universidad de Granada, Granada, 18071, Spain
| | - Cristina Gómez-Martín
- Department of Genetics, Faculty of Sciences, University of Granada, 18071, Granada, Spain
- Laboratory of Bioinformatics, Institute of Biotechnology, Center of Biomedical Research, 18100, Granada, Spain
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Silvia Castiglione
- Dipartimento di Scienze della Terra, dell'Ambiente e delle Risorse, Università di Napoli Federico II, Napoli, 80126, Italy
| | - Pasquale Raia
- Dipartimento di Scienze della Terra, dell'Ambiente e delle Risorse, Università di Napoli Federico II, Napoli, 80126, Italy
| | - Miguel Verdú
- Centro de Investigaciones sobre Desertificación, Consejo Superior de Investigaciones Científicas (CSIC), University of València and Generalitat Valenciana, 46113, Valencia, Spain
| | - Andrés Moya
- Institute of Integrative Systems Biology (I2sysbio), University of València and Consejo Superior de Investigaciones Científicas (CSIC), 46980, Valencia, Spain.
- Foundation for the Promotion of Sanitary and Biomedical Research of Valencian Community (FISABIO), 46020, Valencia, Spain.
- CIBER in Epidemiology and Public Health, Madrid, 28029, Spain.
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Mohammad Mahmud AS, Andersson P, Bulach D, Duchene S, da Silva AG, Lin C, Seemann T, Howden BP, Stinear TP, Taznin T, Habib MA, Akter S, Banu TA, Sarkar MMH, Goswami B, Jahan I, Khan MS. Molecular Epidemiology of SARS-CoV-2 in Bangladesh. Viruses 2025; 17:517. [PMID: 40284960 PMCID: PMC12031083 DOI: 10.3390/v17040517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 04/29/2025] Open
Abstract
Mutation is one of the most important drivers of viral evolution and genome variability, allowing viruses to potentially evade host immune responses and develop drug resistance. In the context of COVID-19, local genomic surveillance of circulating virus populations is therefore critical. The goals of this study were to describe the distribution of different SARS-CoV-2 lineages, assess their genomic differences, and infer virus importation events in Bangladesh. We individually aligned 1965 SARS-CoV-2 genome sequences obtained between April 2020 and June 2021 to the Wuhan-1 sequence and used the resulting multiple sequence alignment as input to infer a maximum likelihood phylogenetic tree. Sequences were assigned to lineages as described by the hierarchical Pangolin nomenclature scheme. We built a phylogeographic model using the virus population genome sequence variation to infer the number of virus importation events. We observed thirty-four lineages and sub-lineages in Bangladesh, with B.1.1.25 and its sub-lineages D.* (979 sequences) dominating, as well as the Beta variant of concern (VOC) B.1.351 and its sub-lineages B.1.351.* (403 sequences). The earliest B.1.1.25/D.* lineages likely resulted from multiple introductions, some of which led to larger outbreak clusters. There were 570 missense mutations, 426 synonymous mutations, 18 frameshift mutations, 7 deletions, 2 insertions, 10 changes at start/stop codons, and 64 mutations in intergenic or untranslated regions. According to phylogeographic modeling, there were 31 importation events into Bangladesh (95% CI: 27-36). Like elsewhere, Bangladesh has experienced distinct waves of dominant lineages during the COVID-19 pandemic; this study focuses on the emergence and displacement of the first wave-dominated lineage, which contains mutations seen in several VOCs and may have had a transmission advantage over the extant lineages.
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Affiliation(s)
- Abu Sayeed Mohammad Mahmud
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Patiyan Andersson
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (P.A.); (D.B.)
| | - Dieter Bulach
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (P.A.); (D.B.)
| | - Sebastian Duchene
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (S.D.); (T.P.S.)
| | - Anders Goncalves da Silva
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (P.A.); (D.B.)
| | - Chantel Lin
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (P.A.); (D.B.)
| | - Torsten Seemann
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (P.A.); (D.B.)
- Centre for Pathogen Genomics, University of Melbourne, Melbourne, VIC 3000, Australia
| | - Benjamin P. Howden
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (P.A.); (D.B.)
- Centre for Pathogen Genomics, University of Melbourne, Melbourne, VIC 3000, Australia
| | - Timothy P. Stinear
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; (S.D.); (T.P.S.)
- Centre for Pathogen Genomics, University of Melbourne, Melbourne, VIC 3000, Australia
| | - Tarannum Taznin
- Department of Microbiology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md. Ahashan Habib
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Shahina Akter
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Tanjina Akhtar Banu
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Md. Murshed Hasan Sarkar
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Barna Goswami
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Iffat Jahan
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
| | - Md. Salim Khan
- Bangladesh Council of Scientific and Industrial Research, Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh; (A.S.M.M.); (M.M.H.S.)
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Ahmad S, Alafnan A, Alobaida A, Shahab U, Rehman S, Khan S, Khan MY, Puri P, Pandey RP, Ahmad I, Rafi Z. Decoding the SARS-CoV-2 infection process: Insights into origin, spread, and therapeutic approaches. Microb Pathog 2025; 200:107328. [PMID: 39863091 DOI: 10.1016/j.micpath.2025.107328] [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: 08/09/2024] [Revised: 10/29/2024] [Accepted: 01/22/2025] [Indexed: 01/27/2025]
Abstract
Globally, over 768 million confirmed cases and 6.9 million deaths had been documented as of July 17, 2023. Coronaviruses have a relatively large RNA genome. As with other viruses, SARS-CoV-2 does have an envelope film produced from host cells that are assisted by virally encoded glycoproteins that are required for infectivity, immunological assault, and viral particle production. Although the intermediate source of origin and transmission to humans is unexplained, rapid transmission from human to human has been established. This review focuses on the mechanistic framework for understanding the SARS-CoV-2 viral infection. Additionally, it discusses the origins and implications of COVID-19 using direct quotations from the published scientific literature to avoid misinterpretation of this catastrophic event that resulted in a massive loss of human life and impact on the global economy. The current available information unfolds large number of topics related with COVID-19 and/or the coronavirus (SARS-CoV-2) responsible of the disease. This review article also delves into the multifaceted aspects of COVID-19 and SARS-CoV-2, with a specific focus on a controversial yet essential issue: the possible association between SARS-CoV-2's origin and aldose reductase, an enzyme known for its role in diabetic retinopathy. Exploring this connection holds utmost significance, offering valuable insights into COVID-19's pathogenesis and unlocking new avenues for therapeutic interventions. It is important to trace back the evolution of coronaviruses and reveal the possible origin of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19).
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Affiliation(s)
- Saheem Ahmad
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, 2440, Saudi Arabia.
| | - Ahmed Alafnan
- Department of Pharmacology, College of Pharmacy, University of Hail, Hail City, 2440, Saudi Arabia.
| | - Ahmed Alobaida
- Department of Pharmacology, College of Pharmacy, University of Hail, Hail City, 2440, Saudi Arabia.
| | - Uzma Shahab
- Department of Pharmacology, College of Pharmacy, University of Hail, Hail City, 2440, Saudi Arabia.
| | - Shahnawaz Rehman
- IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, U.P., India.
| | - Saif Khan
- Department of Basic Dental and Medical Sciences, College of Dentistry, University of Hail, 2440, Hail, 2440, Saudi Arabia.
| | - Mohd Yasir Khan
- Department of Biotechnology, School of Applied & Life Science, Uttaranchal University Dehradun, India.
| | - Paridhi Puri
- University Centre for Research and Development, Chandigarh University, Mohali, Punjab, India.
| | - Ramendra Pati Pandey
- Department of Biotechnology, SRM University, Delhi-NCR, Sonepat, Haryana, 131029, India.
| | - Irfan Ahmad
- Central Labs, King Khalid University, AlQura'a, P.O. Box 960, Abha, Saudi Arabia; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
| | - Zeeshan Rafi
- Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, 226026, India.
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Liu Y, Wang B. Advanced applications in chronic disease monitoring using IoT mobile sensing device data, machine learning algorithms and frame theory: a systematic review. Front Public Health 2025; 13:1510456. [PMID: 40061474 PMCID: PMC11885302 DOI: 10.3389/fpubh.2025.1510456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 01/20/2025] [Indexed: 05/13/2025] Open
Abstract
The escalating demand for chronic disease management has presented substantial challenges to traditional methods. However, the emergence of Internet of Things (IoT) and artificial intelligence (AI) technologies offers a potential resolution by facilitating more precise chronic disease management through data-driven strategies. This review concentrates on the utilization of IoT mobile sensing devices in managing major chronic diseases such as cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes. It scrutinizes their efficacy in disease diagnosis and management when integrated with machine learning algorithms, such as ANN, SVM, RF, and deep learning models. Through an exhaustive literature review, this study dissects how these technologies aid in risk assessment, personalized treatment planning, and disease management. This research addresses a gap in the existing literature concerning the application of IoT and AI technologies in the management of specific chronic diseases. It particularly demonstrates methodological novelty by introducing advanced models based on deep learning, tight frame-based methodologies and real-time monitoring systems. This review employs a rigorous examination method, which includes systematically searching relevant databases, filtering literature that meets specific inclusion and exclusion criteria, and adopting quality assessment tools to ensure the rigor of selected studies. This study identifies potential biases and weaknesses related to data collection, algorithm selection, and user interaction. The research demonstrates that platforms integrating IoT and machine learning algorithms for chronic disease monitoring and management are not only technically viable but also yield substantial economic and social advantages in real-world applications. Future studies could investigate the use of quantum computing for processing vast medical datasets and novel techniques that merge biosensors with nanotechnology for drug delivery and disease surveillance. Furthermore, this paper examines recent progress in medical image reconstruction, emphasizing tight frame-based methodologies. We discuss the principles, benefits, and constraints of these methods, assessing their efficacy across diverse application contexts.
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Affiliation(s)
- Yu Liu
- Hefei University of Technology, Hefei, China
| | - Boyuan Wang
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
- Beijing Xiaotangshan Hospital, Beijing, China
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Li Y, Hu J, Hou J, Lu S, Xiong J, Wang Y, Sun Z, Chen W, Pan Y, Thilakavathy K, Feng Y, Jiang Q, Wang W, Xiong C. Study on sentinel hosts for surveillance of future COVID-19-like outbreaks. Sci Rep 2024; 14:24595. [PMID: 39427096 PMCID: PMC11490639 DOI: 10.1038/s41598-024-76506-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 10/14/2024] [Indexed: 10/21/2024] Open
Abstract
The spread of SARS-CoV-2 to animals has the potential to evolve independently. In this study, we distinguished several sentinel animal species and genera for monitoring the re-emergence of COVID-19 or the new outbreak of COVID-19-like disease. We analyzed SARS-CoV-2 genomic data from human and nonhuman mammals in the taxonomic hierarchies of species, genus, family and order of their host. We find that SARS-CoV-2 carried by domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison), and white-tailed deer (Odocoileus virginianus) cluster closely to human-origin viruses and show no differences in the majority of amino acids, but have the most positively selected sites and should be monitored to prevent the re-emergence of COVID-19 caused by novel variants of SARS-CoV-2. Viruses from the genera Panthera (especially lion (Panthera leo)), Manis and Rhinolophus differ significantly from human-origin viruses, and long-term surveillance should be undertaken to prevent the future COVID-19-like outbreaks. Investigation of the variation dynamics of sites 142, 501, 655, 681 and 950 within the S protein may be necessary to predict the novel animal SARS-CoV-2 variants.
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Affiliation(s)
- Yanjiao Li
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Jingjing Hu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Jingjing Hou
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China
| | - Shuiping Lu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Jiasheng Xiong
- Division of Emergency Management, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, China
| | - Yuxi Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Zhong Sun
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Malaysia
| | - Weijie Chen
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Yue Pan
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Karuppiah Thilakavathy
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Malaysia
| | - Yi Feng
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
| | - Qingwu Jiang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China
| | - Weibing Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China.
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China.
| | - Chenglong Xiong
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China.
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China.
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Patel DK, Kumar H, Sobhia ME. Exploring the binding dynamics of covalent inhibitors within active site of PL pro in SARS-CoV-2. Comput Biol Chem 2024; 112:108132. [PMID: 38959551 DOI: 10.1016/j.compbiolchem.2024.108132] [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: 02/27/2024] [Revised: 06/03/2024] [Accepted: 06/19/2024] [Indexed: 07/05/2024]
Abstract
In the global fight against the COVID-19 pandemic caused by the highly transmissible SARS-CoV-2 virus, the search for potent medications is paramount. With a focused investigation on the SARS-CoV-2 papain-like protease (PLpro) as a promising therapeutic target due to its pivotal role in viral replication and immune modulation, the catalytic triad of PLpro comprising Cys111, His272, and Asp286, highlights Cys111 as an intriguing nucleophilic center for potential covalent bonds with ligands. The detailed analysis of the binding site unveils crucial interactions with both hydrophobic and polar residues, demonstrating the structural insights of the cavity and deepening our understanding of its molecular landscape. The sequence of PLpro among variants of concern (Alpha, Beta, Gamma, Delta and Omicron) and the recent variant of interest, JN.1, remains conserved with no mutations at the active site. Moreover, a thorough exploration of apo, non-covalently bound, and covalently bound PLpro conformations exposes significant conformational changes in loop regions, offering invaluable insights into the intricate dynamics of ligand-protein complex formation. Employing strategic in silico medication repurposing, this study swiftly identifies potential molecules for target inhibition. Within the domain of covalent docking studies and molecular dynamics, using reported inhibitors and clinically tested molecules elucidate the formation of stable covalent bonds with the cysteine residue, laying a robust foundation for potential therapeutic applications. These details not only deepen our comprehension of PLpro inhibition but also play a pivotal role in shaping the dynamic landscape of COVID-19 treatment strategies.
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Affiliation(s)
- Deepesh Kumar Patel
- Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India
| | - Harish Kumar
- Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India
| | - M Elizabeth Sobhia
- Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India.
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Tanrıverdi Ö, Alkan A, Karaoglu T, Kitaplı S, Yildiz A. COVID-19 and Carcinogenesis: Exploring the Hidden Links. Cureus 2024; 16:e68303. [PMID: 39350850 PMCID: PMC11441415 DOI: 10.7759/cureus.68303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2024] [Indexed: 10/04/2024] Open
Abstract
The COVID-19 pandemic caused by the SARS-CoV-2 virus has been studied predominantly in terms of its immediate respiratory and systemic effects. However, emerging evidence suggests possible long-term effects, including its role in carcinogenesis. This comprehensive review explores the complex relationship between COVID-19 and cancer development, focusing on immune dysregulation, chronic inflammation, genetic and epigenetic alterations, and the impact of therapeutic interventions. We also focused on the molecular mechanisms by which SARS-CoV-2 may facilitate cancer progression, including the roles of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and FURIN. Additionally, we examined the possible carcinogenic effects of long-term COVID-19 treatments and the interaction between co-infections and cancer risk. Our findings highlight the need for increased cancer surveillance in COVID-19 survivors. In the post-COVID-19 period, it can be thought that inflammation associated with excessive cytokine release, especially interleukin-6, genetic and epigenetic changes, and co-infections with oncogenic viruses such as Epstein-Barr virus or human papillomavirus may be effective in the development and progression of cancer. Further research is needed to explain the mechanisms underlying this relationship.
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Affiliation(s)
- Özgür Tanrıverdi
- Medical Oncology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
| | - Ali Alkan
- Medical Oncology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
| | | | - Sait Kitaplı
- Medical Oncology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
| | - Aysegul Yildiz
- Molecular Biology and Genetics, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR
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9
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Shao HH, Yin RX. Pathogenic mechanisms of cardiovascular damage in COVID-19. Mol Med 2024; 30:92. [PMID: 38898389 PMCID: PMC11186295 DOI: 10.1186/s10020-024-00855-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 06/07/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. PURPOSE This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. METHODS An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. RESULTS The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. CONCLUSIONS Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.
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Affiliation(s)
- Hong-Hua Shao
- Department of Infectious Diseases, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, No. 1 Erli, Changgang Road, Nanning, Guangxi, 530023, People's Republic of China
| | - Rui-Xing Yin
- Department of Infectious Diseases, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, No. 1 Erli, Changgang Road, Nanning, Guangxi, 530023, People's Republic of China.
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.
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10
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Moneshwaran S, Macrin D, Kanagathara N. An unprecedented global challenge, emerging trends and innovations in the fight against COVID-19: A comprehensive review. Int J Biol Macromol 2024; 267:131324. [PMID: 38574936 DOI: 10.1016/j.ijbiomac.2024.131324] [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: 06/16/2023] [Revised: 03/30/2024] [Accepted: 03/30/2024] [Indexed: 04/06/2024]
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious and dangerous virus that caused the global COVID-19 pandemic in early 2020. It primarily affects the respiratory system, leading to severe illness and high rates of mortality worldwide. The virus enters the body by binding to a receptor called ACE2, which is present in specific cells of the lungs known as type 2 alveolar epithelial cells. Numerous studies have investigated the consequences of SARS-CoV-2 infection, revealing various impacts on the body. This review provides an overview of SARS-CoV-2, including its structure and how it infects cells. It also examines the different variants of concern, such as Alpha, Beta, Gamma, Delta, and the more recent Omicron variant, discussing their characteristics and the level of damage they cause. The usage of drugs to treat COVID-19 is another aspect that has been covered and compares the effectiveness and use of antiviral drugs in the treatment and its potential benefits in COVID-19 treatment. Furthermore, this review explores the consequences and abnormalities associated with SARS-CoV-2 infection, including its impact on various organs and systems in the body. And also discussing the different COVID-19 vaccines available and their effectiveness in preventing infection and reducing the severity of illness. The current review ensures the recent update of the COVID research with expert's knowledge, collection of numerous data from reliable sources and methodologies as well as update of findings based on reviews. This review also provided clear contextual explanations to aid the interpretation and application of the results. The main motto and limitation of this manuscript are to address the computational methods of drug discovery against the rapidly evolving SARS-CoV-2 virus, which has been discussed. Additionally, current computational approaches which are cost effective and can able to predict the therapeutic agents for the treatment against the virus have also been discussed.
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Affiliation(s)
- S Moneshwaran
- Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Thandalam, Chennai 602 105, India
| | - D Macrin
- Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Thandalam, Chennai 602 105, India
| | - N Kanagathara
- Department of Physics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Thandalam, Chennai 602 105, India.
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11
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Silva MJA, Santana DS, Lima MBM, Silva CS, de Oliveira LG, Monteiro EOL, Dias RDS, Pereira BDKB, Nery PADS, Ferreira MAS, Sarmento MADS, Ayin AAN, Mendes de Oliveira AC, Lima KVB, Lima LNGC. Assessment of the Risk Impact of SARS-CoV-2 Infection Prevalence between Cats and Dogs in America and Europe: A Systematic Review and Meta-Analysis. Pathogens 2024; 13:314. [PMID: 38668269 PMCID: PMC11053406 DOI: 10.3390/pathogens13040314] [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: 03/01/2024] [Revised: 03/21/2024] [Accepted: 03/22/2024] [Indexed: 04/29/2024] Open
Abstract
The COVID-19 pandemic represented a huge obstacle for public health and demonstrated weaknesses in surveillance and health promotion systems around the world. Its etiological agent, SARS-CoV-2, of zoonotic origin, has been the target of several studies related to the control and prevention of outbreaks and epidemics of COVID-19 not only for humans but also for animals. Domestic animals, such as dogs and cats, have extensive contact with humans and can acquire the infection both naturally and directly from humans. The objective of this article was to summarize the seroprevalence findings of SARS-CoV-2 in dogs and cats and correlate them with the strength of infection risk between each of them. This is a systematic review and meta-analysis following the recommendations of PRISMA 2020. The search and selection of papers was carried out using in vivo experimental works with animals using the descriptors (MeSH/DeCS) "Animal", "Public Health", "SARS-CoV-2" and "Pandemic" (together with AND) in English, Portuguese or Spanish for Science Direct, PUBMED, LILACS and SciELO databases. The ARRIVE checklist was used for methodological evaluation and the Comprehensive Meta-Analysis v2.2 software with the Difference Risk (RD) test to evaluate statistical inferences (with subgroups by continent). Cats showed greater susceptibility to SARS-CoV-2 compared to dogs both in a joint analysis of studies (RD = 0.017; 95% CI = 0.008-0.025; p < 0.0001) and in the American subgroup (RD = 0.053; 95% CI = 0.032-0.073; p < 0.0001), unlike the lack of significant difference on the European continent (RD = 0.009; 95% CI = -0.001-0.018; p = 0.066). Therefore, it was observed that cats have a greater interest in health surveillance due to the set of biological and ecological aspects of these animals, but also that there are a set of factors that can influence the spread and possible spillover events of the virus thanks to the anthropozoonotic context.
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Affiliation(s)
- Marcos Jessé Abrahão Silva
- Center for Biological and Health Sciences (CCBS), University of the State of Pará (UEPA), Belém 66087-670, PA, Brazil;
| | - Davi Silva Santana
- Institute of Health Sciences (ICS), Institute of Biological Sciences (ICB), Federal University of Pará (UFPA), Belém 66077-830, PA, Brazil; (D.S.S.); (M.B.M.L.); (R.d.S.D.); (M.A.S.F.); (A.C.M.d.O.)
| | - Marceli Batista Martins Lima
- Institute of Health Sciences (ICS), Institute of Biological Sciences (ICB), Federal University of Pará (UFPA), Belém 66077-830, PA, Brazil; (D.S.S.); (M.B.M.L.); (R.d.S.D.); (M.A.S.F.); (A.C.M.d.O.)
| | - Caroliny Soares Silva
- Center for Biological and Health Sciences (CCBS), University of the State of Pará (UEPA), Belém 66087-670, PA, Brazil;
| | - Letícia Gomes de Oliveira
- Evandro Chagas Institute (IEC), Ananindeua 67030-000, PA, Brazil; (L.G.d.O.); (K.V.B.L.); (L.N.G.C.L.)
| | | | - Rafael dos Santos Dias
- Institute of Health Sciences (ICS), Institute of Biological Sciences (ICB), Federal University of Pará (UFPA), Belém 66077-830, PA, Brazil; (D.S.S.); (M.B.M.L.); (R.d.S.D.); (M.A.S.F.); (A.C.M.d.O.)
| | - Bruna de Kássia Barbosa Pereira
- Department of Veterinary Medicine, University of the Amazon (UNAMA), Belém 66120-901, PA, Brazil; (B.d.K.B.P.); (P.A.d.S.N.)
| | - Paula Andresa da Silva Nery
- Department of Veterinary Medicine, University of the Amazon (UNAMA), Belém 66120-901, PA, Brazil; (B.d.K.B.P.); (P.A.d.S.N.)
| | - Márcio André Silva Ferreira
- Institute of Health Sciences (ICS), Institute of Biological Sciences (ICB), Federal University of Pará (UFPA), Belém 66077-830, PA, Brazil; (D.S.S.); (M.B.M.L.); (R.d.S.D.); (M.A.S.F.); (A.C.M.d.O.)
| | | | - Andrea Alexandra Narro Ayin
- Faculty of Medicine, Centro Universitário do Estado do Pará (CESUPA), Belém 66613-903, PA, Brazil; (M.A.d.S.S.); (A.A.N.A.)
| | - Ana Cristina Mendes de Oliveira
- Institute of Health Sciences (ICS), Institute of Biological Sciences (ICB), Federal University of Pará (UFPA), Belém 66077-830, PA, Brazil; (D.S.S.); (M.B.M.L.); (R.d.S.D.); (M.A.S.F.); (A.C.M.d.O.)
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Gerashchenko GV, Hryshchenko NV, Melnichuk NS, Marchyshak TV, Chernushyn SY, Demchyshina IV, Chernenko LM, Kuzin IV, Tkachuk ZY, Kashuba VI, Tukalo MA. Genetic characteristics of SARS-CoV-2 virus variants observed upon three waves of the COVID-19 pandemic in Ukraine between February 2021-January 2022. Heliyon 2024; 10:e25618. [PMID: 38380034 PMCID: PMC10877268 DOI: 10.1016/j.heliyon.2024.e25618] [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: 04/25/2023] [Revised: 12/06/2023] [Accepted: 01/31/2024] [Indexed: 02/22/2024] Open
Abstract
The aim of our study was to identify and characterize the SARS-CoV-2 variants in COVID-19 patients' samples collected from different regions of Ukraine to determine the relationship between SARS-CoV-2 phylogenetics and COVID-19 epidemiology. Patients and methods Samples were collected from COVID-19 patients during 2021 and the beginning of 2022 (401 patients). The SARS-CoV-2 genotyping was performed by parallel whole genome sequencing. Results The obtained SARS-CoV-2 genotypes showed that three waves of the COVID-19 pandemic in Ukraine were represented by three main variants of concern (VOC), named Alpha, Delta and Omicron; each VOC successfully replaced the earlier variant. The VOC Alpha strain was presented by one B.1.1.7 lineage, while VOC Delta showed a spectrum of 25 lineages that had different prevalence in 19 investigated regions of Ukraine. The VOC Omicron in the first half of the pandemic was represented by 13 lines that belonged to two different clades representing B.1 and B.2 Omicron strains. Each of the three epidemic waves (VOC Alpha, Delta, and Omicron) demonstrated their own course of disease, associated with genetic changes in the SARS-CoV-2 genome. The observed epidemiological features are associated with the genetic characteristics of the different VOCs, such as point mutations, deletions and insertions in the viral genome. A phylogenetic and transmission analysis showed the different mutation rates; there were multiple virus sources with a limited distribution between regions. Conclusions The evolution of SARS-CoV-2 virus and high levels of morbidity due to COVID-19 are still registered in the world. Observed multiple virus sourses with the limited distribution between regions indicates the high efficiency of the anti-epidemic policy pursued by the Ministry of Health of Ukraine to prevent the spread of the epidemic, despite the low level of vaccination of the Ukrainian population.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Zenovii Yu Tkachuk
- Institute of Molecular Biology and Genetics of NAS of Ukraine, Kyiv, Ukraine
| | - Vladimir I. Kashuba
- Institute of Molecular Biology and Genetics of NAS of Ukraine, Kyiv, Ukraine
| | - Mykhailo A. Tukalo
- Institute of Molecular Biology and Genetics of NAS of Ukraine, Kyiv, Ukraine
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13
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Sousa BGD, Silva ÍC, Costa RFD, Rebouças ERN, Ramos TR, Almondes JGDS, Pereira EDB, Campos NG. Persistence of symptoms and lung function in mild cases of COVID-19 six months after infection: a cross-sectional study. J Bras Pneumol 2024; 50:e20230305. [PMID: 38422339 PMCID: PMC11095931 DOI: 10.36416/1806-3756/e20230305] [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: 10/09/2023] [Accepted: 11/16/2023] [Indexed: 03/02/2024] Open
Abstract
OBJECTIVES To describe persistent symptoms and lung function in mild cases of COVID-19 six months after infection. METHODS Data collection was performed through a semi-structured questionnaire containing information on the participants' demographic and anthropometric data, the disease in the acute phase, and persistent symptoms six months after COVID-19 using spirometry and manovacuometry. RESULTS A total of 136 participants were evaluated, of whom 64% were male, with a mean age of 38.17 ± 14.08 years and a body mass index (BMI) of 29.71 ± 17.48 kg/m2. The main persistent symptoms reported were dyspnea on exertion (39.7%), memory loss (38.2%), and anxiety (48.5%). Considering lung function, the participants reached 88.87 ± 17.20% of the predicted forced vital capacity (FVC), 86.03 ± 22.01% of the forced expiratory volume in one second (FEV1), and 62.71 ± 25.04% of peak expiratory flow (PEF). Upon manovacuometry, 97.41 ± 34.67% of the predicted inspiratory force (Pimax) and 66.86 ± 22.97% of the predicted expiratory force (Pemax) were observed. CONCLUSIONS Six months after COVID-19 infection, a reduction in PEF and MEP was observed. Among the most commonly reported persistent symptoms were fatigue, tiredness with the slightest exertion, anxiety and depression, memory loss, and deficits in concentration.
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Affiliation(s)
- Barbara Galdino de Sousa
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Grupo de Pesquisa InspiraFisio, Universidade Federal do Ceará, Fortaleza (CE), Brasil
| | - Ítalo Caldas Silva
- . Programa de Pós-Graduação em Ciências Médicas, Departamento de Clínica Médica, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Grupo de Pesquisa InspiraFisio, Universidade Federal do Ceará, Fortaleza (CE), Brasil
| | - Rayana Fialho da Costa
- . Programa de Pós-Graduação em Ciências Médicas, Departamento de Clínica Médica, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Grupo de Pesquisa InspiraFisio, Universidade Federal do Ceará, Fortaleza (CE), Brasil
| | - Ellys Rhaiara Nunes Rebouças
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Grupo de Pesquisa InspiraFisio, Universidade Federal do Ceará, Fortaleza (CE), Brasil
| | - Taynara Rodrigues Ramos
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Grupo de Pesquisa InspiraFisio, Universidade Federal do Ceará, Fortaleza (CE), Brasil
| | | | - Eanes Delgado Barros Pereira
- . Programa de Pós-Graduação em Ciências Médicas, Departamento de Clínica Médica, Universidade Federal do Ceará, Fortaleza (CE), Brasil
| | - Nataly Gurgel Campos
- . Programa de Pós-Graduação em Fisioterapia e Funcionalidade, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Programa de Pós-Graduação em Ciências Médicas, Departamento de Clínica Médica, Universidade Federal do Ceará, Fortaleza (CE), Brasil
- . Grupo de Pesquisa InspiraFisio, Universidade Federal do Ceará, Fortaleza (CE), Brasil
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14
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Silva RS, Souza LMP, Costa RKM, Souza FR, Pimentel AS. Absolute binding free energies of the antiviral peptide ATN-161 with protein targets of SARS-CoV-2. J Biomol Struct Dyn 2023; 41:10546-10557. [PMID: 36476274 DOI: 10.1080/07391102.2022.2154848] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/29/2022] [Indexed: 12/13/2022]
Abstract
The interactions of the antiviral pentapeptide ATN-161 with the closed and open conformations of the α5β1 integrin, the SARS-CoV-2 major protease, and the omicron variant spike protein complexed with hACE2 were studied using molecular docking and molecular dynamics simulation. Molecular docking was performed to obtain ATN-161 binding poses with these studied protein targets. Subsequently, molecular dynamics simulations were performed to verify the ligand stability at the binding site of each protein target. Pulling simulations, umbrella sampling, and weighted histogram analysis method were used to obtain the potential of mean force of each system and calculate the Gibbs free energy of binding for the ATN-161 peptide in each binding site of these protein targets. The results showed that ATN-161 binds to α5β1 integrin in its active and inactive form, binds weakly to the omicron variant spike protein complexed with hACE2, and strongly binds to the main protease target.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Rudielson Santos Silva
- Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Felipe Rodrigues Souza
- Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, Brazil
| | - André Silva Pimentel
- Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, Brazil
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15
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Eleraky NE, El-Badry M, Omar MM, El-Koussi WM, Mohamed NG, Abdel-Lateef MA, Hassan AS. Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2. Int J Nanomedicine 2023; 18:5831-5869. [PMID: 37869062 PMCID: PMC10590117 DOI: 10.2147/ijn.s423251] [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: 06/18/2023] [Accepted: 09/23/2023] [Indexed: 10/24/2023] Open
Abstract
Purpose Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs. Methods Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits. Results The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of -11.23 ± 2.5 mV, and PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration. Conclusion This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies.
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Affiliation(s)
- Nermin E Eleraky
- Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Mahmoud El-Badry
- Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Mahmoud M Omar
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Deraya University, Minia, Egypt
- Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt
| | - Wesam M El-Koussi
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, Egypt
| | - Noha G Mohamed
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sphinx University, Assiut, Egypt
| | - Mohamed A Abdel-Lateef
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Abeer S Hassan
- Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt
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16
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Kaleem S, Sohail A, Tariq MU, Babar M, Qureshi B. Ensemble learning for multi-class COVID-19 detection from big data. PLoS One 2023; 18:e0292587. [PMID: 37819992 PMCID: PMC10566742 DOI: 10.1371/journal.pone.0292587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/25/2023] [Indexed: 10/13/2023] Open
Abstract
Coronavirus disease (COVID-19), which has caused a global pandemic, continues to have severe effects on human lives worldwide. Characterized by symptoms similar to pneumonia, its rapid spread requires innovative strategies for its early detection and management. In response to this crisis, data science and machine learning (ML) offer crucial solutions to complex problems, including those posed by COVID-19. One cost-effective approach to detect the disease is the use of chest X-rays, which is a common initial testing method. Although existing techniques are useful for detecting COVID-19 using X-rays, there is a need for further improvement in efficiency, particularly in terms of training and execution time. This article introduces an advanced architecture that leverages an ensemble learning technique for COVID-19 detection from chest X-ray images. Using a parallel and distributed framework, the proposed model integrates ensemble learning with big data analytics to facilitate parallel processing. This approach aims to enhance both execution and training times, ensuring a more effective detection process. The model's efficacy was validated through a comprehensive analysis of predicted and actual values, and its performance was meticulously evaluated for accuracy, precision, recall, and F-measure, and compared to state-of-the-art models. The work presented here not only contributes to the ongoing fight against COVID-19 but also showcases the wider applicability and potential of ensemble learning techniques in healthcare.
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Affiliation(s)
- Sarah Kaleem
- Department of Computing and Technology, Iqra University, Islamabad, Pakistan
| | | | - Muhammad Usman Tariq
- Abu Dhabi University, Abu Dhabi, UAE
- Universiti Tun Hussein Onn Malaysia (UTHM), Parit Raja, Malaysia
| | - Muhammad Babar
- Robotics and Internet of Things Lab, Prince Sultan University, Riyadh, Saudi Arabia
| | - Basit Qureshi
- College of Computer and Information Sciences, Prince Sultan University, Riyadh, Saudi Arabia
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Chala B, Tilaye T, Waktole G. Re-Emerging COVID-19: Controversy of Its Zoonotic Origin, Risks of Severity of Reinfection and Management. Int J Gen Med 2023; 16:4307-4319. [PMID: 37753439 PMCID: PMC10518360 DOI: 10.2147/ijgm.s419789] [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: 05/21/2023] [Accepted: 08/19/2023] [Indexed: 09/28/2023] Open
Abstract
The re-emergence of COVID-19 has sparked controversy around its zoonotic origin, management strategies, risks posed by the virus, and the severity of reinfection. While it is widely accepted that the virus originated from animals, the exact source and transmission pathway remain unclear. This has led to debates regarding the regulation of wildlife markets and trade, as well as the need for more robust surveillance and monitoring systems. Hence, the objective of this review is to provide a brief overview of the disease's biology, preventative strategies, risk factors, degree of reinfection, and epidemiological profile. It offers a thorough examination of the disease's root cause, potential zoonotic transmission, and the most recent preventive measures, like vaccines. In terms of management, there is ongoing debate about the most effective strategies to mitigate the spread of the virus. While public health measures such as social distancing and mask-wearing have been widely implemented, there are differing opinions on the effectiveness of lockdowns and restrictions on public movement. The risks posed by COVID-19 are also a topic of debate, with some arguing that the virus is relatively low-risk for the majority of the population while others highlight the potential for severe illness, particularly among vulnerable populations such as the elderly or those with underlying health conditions. Finally, the possibility of reinfection has raised concerns about the longevity of immunity following infection or vaccination. While some studies have suggested that reinfection may be possible and potentially more severe, the overall risk remains uncertain and further research is needed to fully understand the implications of reinfection.
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Affiliation(s)
- Bayissa Chala
- Department of Applied Biology, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia
| | - Tigist Tilaye
- Olanchiti Hospital, Oromia Health Bureau, Oromia Regional State, Ethiopia
| | - Gemechis Waktole
- Department of Applied Biology, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia
- Department of Biotechnology, College of Natural and Computational Science, Dambi Dollo University, Dambi Dollo, Ethiopia
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18
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Yang MY, Zheng MH, Meng XT, Ma LW, Liang HY, Fan HY. Role of toll-like receptors in the pathogenesis of COVID-19: Current and future perspectives. Scand J Immunol 2023; 98:e13275. [PMID: 38441378 DOI: 10.1111/sji.13275] [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: 10/22/2022] [Revised: 04/21/2023] [Accepted: 04/24/2023] [Indexed: 03/07/2024]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.
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Affiliation(s)
- Ming-Yan Yang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China
| | - Mei-Hua Zheng
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China
| | - Xiang-Ting Meng
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China
| | - Le-Wei Ma
- Ruikang Pharmaceutical Group Co. Ltd., Yantai, China
| | - Hai-Yue Liang
- Yantai Center for Food and Drug Control, Yantai, China
| | - Hua-Ying Fan
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China
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19
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Giovanetti M, Branda F, Cella E, Scarpa F, Bazzani L, Ciccozzi A, Slavov SN, Benvenuto D, Sanna D, Casu M, Santos LA, Lai A, Zehender G, Caccuri F, Ianni A, Caruso A, Maroutti A, Pascarella S, Borsetti A, Ciccozzi M. Epidemic history and evolution of an emerging threat of international concern, the severe acute respiratory syndrome coronavirus 2. J Med Virol 2023; 95:e29012. [PMID: 37548148 DOI: 10.1002/jmv.29012] [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: 06/05/2023] [Revised: 07/12/2023] [Accepted: 07/20/2023] [Indexed: 08/08/2023]
Abstract
This comprehensive review focuses on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact as the cause of the COVID-19 pandemic. Its objective is to provide a cohesive overview of the epidemic history and evolutionary aspects of the virus, with a particular emphasis on its emergence, global spread, and implications for public health. The review delves into the timelines and key milestones of SARS-CoV-2's epidemiological progression, shedding light on the challenges encountered during early containment efforts and subsequent waves of transmission. Understanding the evolutionary dynamics of the virus is crucial in monitoring its potential for adaptation and future outbreaks. Genetic characterization of SARS-CoV-2 is discussed, with a focus on the emergence of new variants and their implications for transmissibility, severity, and immune evasion. The review highlights the important role of genomic surveillance in tracking viral mutations linked to establishing public health interventions. By analyzing the origins, global spread, and genetic evolution of SARS-CoV-2, valuable insights can be gained for the development of effective control measures, improvement of pandemic preparedness, and addressing future emerging infectious diseases of international concern.
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Affiliation(s)
- Marta Giovanetti
- Instituto Rene Rachou Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
- Sciences and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Italy, Rome, Italy
| | - Francesco Branda
- Department of Computer Science, Modeling, Electronics and Systems Engineering (DIMES), University of Calabria, Rende, Italy
| | - Eleonora Cella
- Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA
| | - Fabio Scarpa
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Liliana Bazzani
- Sciences and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Italy, Rome, Italy
| | - Alessandra Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Svetoslav Nanev Slavov
- Butantan Institute, São Paulo, Brazil
- Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Domenico Benvenuto
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Daria Sanna
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Marco Casu
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
| | - Luciane Amorim Santos
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil
- Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Praça Ramos de Queirós, s/n, Largo do Terreiro de Jesus, Salvador, Bahia, Brazil
| | - Alessia Lai
- Department of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Milan, Italy
| | - Giangluglielmo Zehender
- Department of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Milan, Italy
| | - Francesca Caccuri
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Andrea Ianni
- M.G. Vannini Hospital IFSC Rome, Research Unit in Hygiene UCBM Rome, Rome, Italy
| | - Arnaldo Caruso
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | | | - Stefano Pascarella
- Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy
| | | | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
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20
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Khorasani Esmaili P, Dabiri S, Movahedinia S, Shojaeepour S, Bagheri F, Ranjbar H, Shamsi Meymandi M, Mohebbi E, Farrokhnia M. Evaluation of Laboratory Findings of Patients with Coronavirus Disease 2019 in Kerman, Iran. IRANIAN JOURNAL OF PATHOLOGY 2023; 18:347-355. [PMID: 37942197 PMCID: PMC10628381 DOI: 10.30699/ijp.2023.1971332.3031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 05/30/2023] [Indexed: 11/10/2023]
Abstract
Background & Objective Since December 2019 in Wuhan, China there is a new form of pneumonia and after expansion in other countries, World Health Organization (WHO) called it Coronavirus Disease 2019 (COVID-19). Since the clinical laboratory findings have played an important role in the progression of the disease, this study aimed to evaluate the laboratory findings in COVID-19 patients (before vaccination). Methods In this case-control study that was conducted from February to August 2020; the laboratory test status in 101 positive COVID-19 patients was evaluated and compared with 101 healthy individuals. Results The results of our study showed that 21% of patients had low WBC, 24.75% low RBC, 37.62%, low Hb, 18.81% with low HCT, 29.7%, low Plt, 41.58% had High PT, 71.29% high CRP, 17.82% high urea, 11.88% high CR, 15.84% high LDH, 10.89% low sodium, 14.75% low potassium (K). The quantitative examination of blood factors showed that lymph%, mixed%, PLT, HCT, Hb, and RBC were higher in the control group than in the case group. While Neu%, WBC, PTT, CRP, UREA, LDH, K in the patient group were higher than in the control group. Conclusion According to the results of the study, it can be concluded that in the clinical treatment of COVID-19 patients, much attention should be paid to the laboratory indicators to identify and intervene early in critically ill patients.
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Affiliation(s)
- Parisa Khorasani Esmaili
- Department of Pathology, Pathology and Stem Cells Research Center, Afzali Pour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Shahriar Dabiri
- Department of Pathology, Pathology and Stem Cells Research Center, Afzali Pour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Sajjadeh Movahedinia
- Department of Pathology, Pathology and Stem Cells Research Center, Afzali Pour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Saeedeh Shojaeepour
- Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Fatemeh Bagheri
- Legal Medicine Research Center, Legal Medicine Organization, Kerman, Iran
| | - Hanieh Ranjbar
- Department of Pathology, Pathology and Stem Cells Research Center, Afzali Pour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Manzumeh Shamsi Meymandi
- Department of Pathology, Pathology and Stem Cells Research Center, Afzali Pour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Elham Mohebbi
- Research Center for Modeling in Health, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Mehrdad Farrokhnia
- Infectious and Internal Medicine Department, Afzalipour Hospital, Kerman University of Medical Science, Kerman, Iran
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21
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Agodi A, Maugeri A, Favara G, Magnano San Lio R, Puglisi M, Sinatra D, Liberti G, Barchitta M. Gender differences in comorbidities of patients with COVID-19: An Italian local register-based analysis. Heliyon 2023; 9:e18109. [PMID: 37483834 PMCID: PMC10362315 DOI: 10.1016/j.heliyon.2023.e18109] [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: 01/26/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 07/25/2023] Open
Abstract
In the current COVID-19 pandemic scenario, it is still necessary to understand if differences exist between genders in terms of patients' characteristics and clinical outcomes. For this reason, we retrospectively analyzed data obtained from a local register-based dataset of all SARS-CoV-2 positive patients diagnosed in the province of Catania (Italy). The main aim of this analysis was to understand any differences between genders in the distribution of previous medical conditions, and to evaluate which of them posed individuals at higher risk of death. With this purpose, we analyzed data from 1424 patients with at least one underlying medical condition, who were tested positive for SARS-CoV-2 infection from February 2020 to December 2021. Overall, males were 59.5% of the total population and significantly younger than females (median ages: 68 years vs. 72 years; p = 0.011). The age distribution of cases by gender confirms that individuals from 70 to 79 years were the most affected in both genders. The comparison of underlying comorbidities by gender shows significant differences for diabetes (p < 0.001), other metabolic diseases (p = 0.006), and obesity (p = 0.019). Accordingly, multivariable logistic regression analysis confirmed that diabetes was more likely to be present in males than in females (p = 0.001), while other metabolic diseases and obesity were less likely to be present (p = 0.003 and p = 0.005, respectively). Although no difference in mortality was evident between genders (p = 0.141), both male and female COVID-19 patients had a significantly higher risk of death if they had comorbidities such as CVDs, kidney diseases, or chronic neurological diseases. Moreover, diabetes and chronic respiratory diseases were significant risk factors for COVID-19 mortality among men, whereas cancer was a significant contributor among women. Our findings confirm gender-differences in pre-existing medical conditions of COVID-19 patients, which may influence the risk of death. Further studies, however, are needed to understand physiological and pathological mechanisms underpinning these differences.
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Affiliation(s)
- Antonella Agodi
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, Catania, Italy
| | - Andrea Maugeri
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, Catania, Italy
| | - Giuliana Favara
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, Catania, Italy
| | - Roberta Magnano San Lio
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, Catania, Italy
| | - Martina Puglisi
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, Catania, Italy
| | - Dario Sinatra
- Provincial Health Authority (Azienda Sanitaria Provinciale, ASP) of Catania, Catania, Italy
| | - Giuseppe Liberti
- Provincial Health Authority (Azienda Sanitaria Provinciale, ASP) of Catania, Catania, Italy
| | - Martina Barchitta
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, Catania, Italy
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22
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Gameil MA, Marzouk RE, El-Sebaie AH, Ahmed Eldeeb AA. Influence of time factor and albuminuria on characteristics of patients with type 2 diabetes Mellitus before, during and 1 year after COVID-19 recovery. Diabetol Metab Syndr 2023; 15:126. [PMID: 37312131 DOI: 10.1186/s13098-023-01104-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 06/03/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND The potential effects of time factor and albuminuria on the morbid alterations in patients with type 2 diabetes (T2D) and COVID-19 are still unclear. We aimed to address the morbid alterations and the potential effects of time factor and albuminuria on the patients' characteristics before, during, and 1 year after COVID-19 recovery. METHODS 83 patients with T2D were included, at Mansoura University Hospital, Egypt (July 2021-December 2021). Data of detailed history, physical examination, laboratory tests were recruited from files of the patients. Diagnosis and resolution of COVID-19 were established by Real time polymerase chain reaction (RT-PCR) test of SARS-CoV2. Complete blood count (CBC), renal and hepatic function tests, multiple measures of morning spot urine albumin to creatinine ratio (urine ACR), glycosylated hemoglobin (HBA1c), lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ferritin, neutrophil to lymphocyte ratio (NLR), vitamin D3, intact parathyroid hormone (intact PTH), serum calcium were applied to all participants. RESULTS Our participants had a mean age of 45 years, 60.2% male, 56.6% were hospitalized, and 25.3% were admitted to ICU for severe COVID-19. Albuminuria was prevalent in 71.1% before, 98.8% during, and 92.8% after COVID-19 recovery. Patients with albuminuria showed older age, longer duration of T2D, more frequent severe COVID-19 and hospitalization (p = 0.03, p < 0.001, p = 0.023& p = 0.025) respectively. Body mass index (BMI), mean arterial blood pressure, ESR, CRP, ferritin, NLR, HBA1c, triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio, vitamin D3, serum calcium, alkaline phosphatase (ALP), hepatic aminotransferases, and urine ACR showed significant alterations throughout the study (p < 0.001 for all). Although the interaction between time and albuminuria showed non-significant effect on all studied parameters, we noticed relevant main effects of time factor on Body mass index (BMI), HBA1c, glomerular filtration rate (eGFR), TG/HDL ratio, NLR, vitamin D3, (p < 0.001 for all). Moreover, albuminuria showed main effects on BMI, serum creatinine, and intact PTH (p = 0.019, 0.005 & <0.001), respectively. CONCLUSION The characteristics of patients with T2D significantly altered throughout the study. Time factor and albuminuria exerted relevant main effects on the patients' characteristics without significant effect of their interaction.
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Affiliation(s)
- Mohammed Ali Gameil
- Endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Rehab Elsayed Marzouk
- Lecturer of Medical Biochemistry, Medical Biochemistry Department, Faculty of Medicine, Helwan University, Helwan, 0000-0002, 5551- 1540, Cairo, Egypt
| | - Ahmed Hassan El-Sebaie
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt
| | - Ahmed Ahmed Ahmed Eldeeb
- Associate professor of Internal medicine, Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, 0000-0002, 3238-3064, Dakahlia, Egypt
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23
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Su Y, Wu J, Li X, Li J, Zhao X, Pan B, Huang J, Kong Q, Han J. DTSEA: A network-based drug target set enrichment analysis method for drug repurposing against COVID-19. Comput Biol Med 2023; 159:106969. [PMID: 37105108 PMCID: PMC10121077 DOI: 10.1016/j.compbiomed.2023.106969] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 03/27/2023] [Accepted: 04/19/2023] [Indexed: 04/29/2023]
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic is still wreaking havoc worldwide. Therefore, the urgent need for efficient treatments pushes researchers and clinicians into screening effective drugs. Drug repurposing may be a promising and time-saving strategy to identify potential drugs against this disease. Here, we developed a novel computational approach, named Drug Target Set Enrichment Analysis (DTSEA), to identify potent drugs against COVID-19. DTSEA first mapped the disease-related genes into a gene functional interaction network, and then it used a network propagation algorithm to rank all genes in the network by calculating the network proximity of genes to disease-related genes. Finally, an enrichment analysis was performed on drug target sets to prioritize disease-candidate drugs. It was shown that the top three drugs predicted by DTSEA, including Ataluren, Carfilzomib, and Aripiprazole, were significantly enriched in the immune response pathways indicating the potential for use as promising COVID-19 inhibitors. In addition to these drugs, DTSEA also identified several drugs (such as Remdesivir and Olumiant), which have obtained emergency use authorization (EUA) for COVID-19. These results indicated that DTSEA could effectively identify the candidate drugs for COVID-19, which will help to accelerate the development of drugs for COVID-19. We then performed several validations to ensure the reliability and validity of DTSEA, including topological analysis, robustness analysis, and prediction consistency. Collectively, DTSEA successfully predicted candidate drugs against COVID-19 with high accuracy and reliability, thus making it a formidable tool to identify potential drugs for a specific disease and facilitate further investigation.
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Affiliation(s)
- Yinchun Su
- Department of Neurobiology, Harbin Medical University, Harbin, 150081, PR China
| | - Jiashuo Wu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China
| | - Xiangmei Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China
| | - Ji Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China
| | - Xilong Zhao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China
| | - Bingyue Pan
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China
| | - Junling Huang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China
| | - Qingfei Kong
- Department of Neurobiology, Harbin Medical University, Harbin, 150081, PR China.
| | - Junwei Han
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, PR China.
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Santucci F, Nobili M, Faramondi L, Oliva G, Mazzà B, Scala A, Ciccozzi M, Setola R. Evaluating the COVID-19 impact in Italian regions via multi criteria analysis. PLoS One 2023; 18:e0285452. [PMID: 37163510 PMCID: PMC10171687 DOI: 10.1371/journal.pone.0285452] [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: 01/24/2023] [Accepted: 04/24/2023] [Indexed: 05/12/2023] Open
Abstract
Italy was the first European country to be significantly impacted by the COVID-19 pandemic. The lack of similar previous experiences and the initial uncertainty regarding the new virus resulted in an unpredictable health crisis with 243,506 total confirmed cases and 34,997 deaths between February and July 2020. Despite the panorama of precariousness and the impelling calamity, the country successfully managed many aspects of the early stages of the health and socio-economic crisis. Nevertheless, many disparities can be identified at the regional level. The study aims to determine which aspects of regional management were considered more important by the citizens regarding economic and health criteria. A survey was designed to gather responses from the population on the Italian regions' response and provide a ranking of the regions. The 29-item online survey was provided to 352 individuals, and the collected data were analyzed using the Analytic Hierarchy Process methodology. The results show a general agreement in considering of greater relevance the healthcare policies rather than the economic countermeasures adopted by regional governments. Our analysis associated a weight of 64% to the healthcare criteria compared to the economic criteria with a weight of 36%. In addition to the results obtained from the Analytic Hierarchy Process, the sample's composition was analyzed to provide an overall assessment of the Italian regions. To do so, we collected objective data for each region and multiplied them by the overall weight obtained for each sub-criteria. Looking at the propensity to vaccination or the belief in a relation between COVID-19 and 5G according to age and educational qualification helps understand how public opinion is structured according to cultural and anthropological differences.
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Affiliation(s)
- Francesca Santucci
- Unit of Automatic Control, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Martina Nobili
- Unit of Automatic Control, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Luca Faramondi
- Unit of Automatic Control, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Gabriele Oliva
- Unit of Automatic Control, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Bianca Mazzà
- Unit of Automatic Control, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Antonio Scala
- ISC-CNR Physics Department, Università La Sapienza, Roma, Italy
- Global Health Security Agenda – GHSA Italy
| | - Massimo Ciccozzi
- Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, Rome, Italy
| | - Roberto Setola
- Unit of Automatic Control, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
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25
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Systematic Guidelines for Effective Utilization of COVID-19 Databases in Genomic, Epidemiologic, and Clinical Research. Viruses 2023; 15:v15030692. [PMID: 36992400 PMCID: PMC10059256 DOI: 10.3390/v15030692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/27/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
The pandemic has led to the production and accumulation of various types of data related to coronavirus disease 2019 (COVID-19). To understand the features and characteristics of COVID-19 data, we summarized representative databases and determined the data types, purpose, and utilization details of each database. In addition, we categorized COVID-19 associated databases into epidemiological data, genome and protein data, and drug and target data. We found that the data present in each of these databases have nine separate purposes (clade/variant/lineage, genome browser, protein structure, epidemiological data, visualization, data analysis tool, treatment, literature, and immunity) according to the types of data. Utilizing the databases we investigated, we created four queries as integrative analysis methods that aimed to answer important scientific questions related to COVID-19. Our queries can make effective use of multiple databases to produce valuable results that can reveal novel findings through comprehensive analysis. This allows clinical researchers, epidemiologists, and clinicians to have easy access to COVID-19 data without requiring expert knowledge in computing or data science. We expect that users will be able to reference our examples to construct their own integrative analysis methods, which will act as a basis for further scientific inquiry and data searching.
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26
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Câmara AB, Bonfante J, da Penha MG, Cassini STA, de Pinho Keller R. Detecting SARS-CoV-2 in sludge samples: A systematic review. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 859:160012. [PMID: 36368397 PMCID: PMC9643039 DOI: 10.1016/j.scitotenv.2022.160012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 06/16/2023]
Abstract
AIMS This paper aims to review the main sludge concentration methods used for SARS-CoV-2 detection in sewage sludge samples, discussing the main methods and sample volume related to increased viral load. In addition, we aim to evaluate the countries associated with increased positivity rates for SARS-CoV-2 in sludge samples. METHODS This systematic methodology was registered in PROSPERO and followed the PRISMA guidelines. The search was carried out in the SciELO, PubMed/MEDLINE, Lilacs, and Google Scholar databases in January-March 2022. Quantitative studies with conclusive results were included in this review. Concentration methods (polyethylene glycol (PEG), PEG + NaCl, gravity thickening, skimmed milk flocculation, ultrafiltration, filtration using charged filters, primary sedimentation, and anaerobic digestion), as well as detection methods (RTqPCR and reverse transcription droplet digital PCR assay) were evaluated in this review. The SPSS v23 software program was used for statistical analysis. RESULTS PEG (with or without NaCl addition) and gravity thickening were the most used sludge concentration methods to detect SARS-CoV-2. The main method associated with increased viral load (>2,02 × 10^4 copies/mL) was PEG + NaCl (p < 0.05, Mann-Whitney test). The average positivity rate for SARS-CoV-2 in sludge samples was 61 %, and a correlation was found between the sludge volume and the viral load (ro 0.559, p = 0.03, Spearman correlation). CONCLUSION The sludge volume may influence the SARS-CoV-2 load since the virus can adhere to solid particles in these samples. Other factors may be associated with SARS-CoV-2 load, including the methods used; especially PEG + NaCl may result in a high viral load detected in sludge, and may provide a suitable pH for SARS-CoV-2 recovery.
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Affiliation(s)
- Alice Barros Câmara
- Sanitation Laboratory, Department of Environmental Engineering, Universidade Federal do Espírito Santo, Ave. Fernando Ferrari, 515, Goiabeiras, 29075051 Vitória, ES, Brazil.
| | - Júlia Bonfante
- Sanitation Laboratory, Department of Environmental Engineering, Universidade Federal do Espírito Santo, Ave. Fernando Ferrari, 515, Goiabeiras, 29075051 Vitória, ES, Brazil
| | - Marília Gueler da Penha
- Sanitation Laboratory, Department of Environmental Engineering, Universidade Federal do Espírito Santo, Ave. Fernando Ferrari, 515, Goiabeiras, 29075051 Vitória, ES, Brazil
| | - Sérvio Túlio Alves Cassini
- Sanitation Laboratory, Department of Environmental Engineering, Universidade Federal do Espírito Santo, Ave. Fernando Ferrari, 515, Goiabeiras, 29075051 Vitória, ES, Brazil
| | - Regina de Pinho Keller
- Sanitation Laboratory, Department of Environmental Engineering, Universidade Federal do Espírito Santo, Ave. Fernando Ferrari, 515, Goiabeiras, 29075051 Vitória, ES, Brazil
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Prabhakar PK, Khurana N, Vyas M, Sharma V, Batiha GES, Kaur H, Singh J, Kumar D, Sharma N, Kaushik A, Kumar R. Aspects of Nanotechnology for COVID-19 Vaccine Development and Its Delivery Applications. Pharmaceutics 2023; 15:pharmaceutics15020451. [PMID: 36839773 PMCID: PMC9960567 DOI: 10.3390/pharmaceutics15020451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/21/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Coronavirus, a causative agent of the common cold to a much more complicated disease such as "severe acute respiratory syndrome (SARS-CoV-2), Middle East Respiratory Syndrome (MERS-CoV-2), and Coronavirus Disease 2019 (COVID-19)", is a member of the coronaviridae family and contains a positive-sense single-stranded RNA of 26-32 kilobase pairs. COVID-19 has shown very high mortality and morbidity and imparted a significantly impacted socioeconomic status. There are many variants of SARS-CoV-2 that have originated from the mutation of the genetic material of the original coronavirus. This has raised the demand for efficient treatment/therapy to manage newly emerged SARS-CoV-2 infections successfully. However, different types of vaccines have been developed and administered to patients but need more attention because COVID-19 is not under complete control. In this article, currently developed nanotechnology-based vaccines are explored, such as inactivated virus vaccines, mRNA-based vaccines, DNA-based vaccines, S-protein-based vaccines, virus-vectored vaccines, etc. One of the important aspects of vaccines is their administration inside the host body wherein nanotechnology can play a very crucial role. Currently, more than 26 nanotechnology-based COVID-19 vaccine candidates are in various phases of clinical trials. Nanotechnology is one of the growing fields in drug discovery and drug delivery that can also be used for the tackling of coronavirus. Nanotechnology can be used in various ways to design and develop tools and strategies for detection, diagnosis, and therapeutic and vaccine development to protect against COVID-19. The design of instruments for speedy, precise, and sensitive diagnosis, the fabrication of potent sanitizers, the delivery of extracellular antigenic components or mRNA-based vaccines into human tissues, and the administration of antiretroviral medicines into the organism are nanotechnology-based strategies for COVID-19 management. Herein, we discuss the application of nanotechnology in COVID-19 vaccine development and the challenges and opportunities in this approach.
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Affiliation(s)
| | - Navneet Khurana
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab 144411, India
- Correspondence: (N.K.); (R.K.)
| | - Manish Vyas
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab 144411, India
| | - Vikas Sharma
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab 144411, India
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
| | - Harpreet Kaur
- School of Chemical Engineering and Physical Sciences, Lovely Professional University, Punjab 144411, India
| | - Jashanpreet Singh
- School of Chemical Engineering and Physical Sciences, Lovely Professional University, Punjab 144411, India
| | - Deepak Kumar
- School of Chemical Engineering and Physical Sciences, Lovely Professional University, Punjab 144411, India
| | - Neha Sharma
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab 144411, India
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Department of Environmental Engineering, Florida Polytechnic University, Lakeland, FL 33805, USA
- School of Engineering, University of Petroleum and Energy Studies (UPES), Uttarakhand 248007, India
| | - Raj Kumar
- Department of Pharmaceutical Sciences, University of Nebraska Medical Sciences, Omaha, NE 68198, USA
- Correspondence: (N.K.); (R.K.)
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Kumar N, Santhoshkumar R, Prasad P, George AK, Aiyar J, Joshi S, Narayanappa G, Desai AS, Ravi V, Venkataswamy MM. An ultrastructural and genomic study on the SARS-CoV-2 variant B.1.210 circulating during the first wave of COVID-19 pandemic in India. Indian J Med Microbiol 2023; 41:45-52. [PMID: 36870749 PMCID: PMC9822079 DOI: 10.1016/j.ijmmb.2022.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 11/02/2022] [Accepted: 12/23/2022] [Indexed: 01/09/2023]
Abstract
PURPOSE The study aims to isolate and understand cytopathogenesis, ultrastructure, genomic characteristics and phylogenetic analysis of SARS-CoV-2 virus of B.1.210 lineage, that circulated in India during first wave of the pandemic. METHODS Clinical specimen from an interstate traveller from Maharashtra to Karnataka, in May 2020, who was positive by RT PCR for SARS-CoV-2 infection was subjected to virus isolation and Whole Genome Sequencing. Vero cells were used to study cytopathogenesis and ultrastructural features by Transmission Electron Microscopy (TEM). Phylogenetic analysis of the whole genome sequences of several SARS-CoV-2 variants downloaded from GISAID was performed in comparison with the B.1.210 variant identified in this study. RESULTS The virus was isolated in Vero cells and identified by immunofluorescence assay and RT PCR. The growth kinetics in infected Vero cells revealed a peak viral titre at 24 h post-infection. Ultrastructural studies revealed distinct morphological changes with accumulation of membrane-bound vesicles containing pleomorphic virions in the cytoplasm, with single or multiple intranuclear filamentous inclusions and dilated rough endoplasmic reticulum with viral particles. Whole genome sequence of the clinical specimen as well as the isolated virus revealed the virus to be of lineage B.1.210 with the D614G mutation in the spike protein. Phylogenetic analysis of the whole genome sequence in comparison with other variants reported globally revealed that the isolated SARS-CoV-2 virus of lineage B.1.210 is closely related to the original Wuhan virus reference sequence. CONCLUSIONS The SARS-CoV-2 variant B.1.210 virus isolated here showed ultrastructural features and cytopathogenesis similar to that of the virus reported during early phase of pandemic. Phylogenetic analysis showed that the isolated virus is closely related to the original Wuhan virus, thereby suggesting that the SARS-CoV-2 lineage B.1.210 that was circulating in India during the early phase of pandemic is likely to have evolved from the original Wuhan strain.
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Affiliation(s)
- Narendra Kumar
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Rashmi Santhoshkumar
- Electron Microscopy -Common Research Facility, Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Pramada Prasad
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Anson K George
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Jayashree Aiyar
- Discovery Biology, Syngene International Limited, Bengaluru, India
| | - Saurabh Joshi
- Discovery Biology, Syngene International Limited, Bengaluru, India
| | - Gayathri Narayanappa
- Electron Microscopy -Common Research Facility, Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Anita S Desai
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Vasanthapuram Ravi
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bengaluru, India
| | - Manjunatha M Venkataswamy
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
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Bello M, Hasan MK. Elucidation of the inhibitory activity of plant-derived SARS-CoV inhibitors and their potential as SARS-CoV-2 inhibitors. J Biomol Struct Dyn 2022; 40:9992-10004. [PMID: 34121618 DOI: 10.1080/07391102.2021.1938234] [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
Several drugs are now being tested as possible therapies due to the necessity of treating SARS-CoV-2 infection. Although approved vaccines bring much hope, a vaccination program covering the entire global population will take a very long time, making the development of effective antiviral drugs an effective solution for the immediate treatment of this dangerous infection. Previous studies found that three natural compounds, namely, tannic acid, 3-isotheaflavin-3-gallate and theaflavin-3,3-digallate, are effective proteinase (3CLpro) inhibitors of SARS-CoV (IC50 <10 µM). Based on this information and due to the high sequence identity between SARS-CoV and SARS-CoV-2 3CLpro, these three compounds could be candidate inhibitors of SARS-CoV-2 3CLpro. This paper explores the structural and energetic features that guided the molecular recognition of these three compounds for dimeric SARS-CoV-2 and SARS-CoV 3CLpro, the functional state of this enzyme, using docking and MD simulations with the molecular mechanics-generalized-born surface area (MMGBSA) approach. Energetic analysis demonstrated that the three compounds reached good affinities in both systems in the following order: tannic acid > 3-isotheaflavin-3-gallate > theaflavin-3,3-digallate. This tendency is in line with that experimentally reported between these ligands and SARS-CoV 3CLpro. Therefore, tannic acid may have clinical usefulness against COVID-19 by acting as a potent inhibitor of SARS-CoV-2 3CLpro.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Martiniano Bello
- Laboratorio de Modelado Molecular, Bioinformática y Diseño de Fármacos de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, México
| | - Md Kamrul Hasan
- Department of Biochemistry and Molecular Biology, Tejgaon College, National University, Gazipur, Bangladesh
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Lucaci AG, Zehr JD, Shank SD, Bouvier D, Ostrovsky A, Mei H, Nekrutenko A, Martin DP, Kosakovsky Pond SL. RASCL: Rapid Assessment of Selection in CLades through molecular sequence analysis. PLoS One 2022; 17:e0275623. [PMID: 36322581 PMCID: PMC9629619 DOI: 10.1371/journal.pone.0275623] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 09/20/2022] [Indexed: 11/06/2022] Open
Abstract
An important unmet need revealed by the COVID-19 pandemic is the near-real-time identification of potentially fitness-altering mutations within rapidly growing SARS-CoV-2 lineages. Although powerful molecular sequence analysis methods are available to detect and characterize patterns of natural selection within modestly sized gene-sequence datasets, the computational complexity of these methods and their sensitivity to sequencing errors render them effectively inapplicable in large-scale genomic surveillance contexts. Motivated by the need to analyze new lineage evolution in near-real time using large numbers of genomes, we developed the Rapid Assessment of Selection within CLades (RASCL) pipeline. RASCL applies state of the art phylogenetic comparative methods to evaluate selective processes acting at individual codon sites and across whole genes. RASCL is scalable and produces automatically updated regular lineage-specific selection analysis reports: even for lineages that include tens or hundreds of thousands of sampled genome sequences. Key to this performance is (i) generation of automatically subsampled high quality datasets of gene/ORF sequences drawn from a selected "query" viral lineage; (ii) contextualization of these query sequences in codon alignments that include high-quality "background" sequences representative of global SARS-CoV-2 diversity; and (iii) the extensive parallelization of a suite of computationally intensive selection analysis tests. Within hours of being deployed to analyze a novel rapidly growing lineage of interest, RASCL will begin yielding JavaScript Object Notation (JSON)-formatted reports that can be either imported into third-party analysis software or explored in standard web-browsers using the premade RASCL interactive data visualization dashboard. By enabling the rapid detection of genome sites evolving under different selective regimes, RASCL is well-suited for near-real-time monitoring of the population-level selective processes that will likely underlie the emergence of future variants of concern in measurably evolving pathogens with extensive genomic surveillance.
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Affiliation(s)
- Alexander G. Lucaci
- Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
| | - Jordan D. Zehr
- Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
| | - Stephen D. Shank
- Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
| | - Dave Bouvier
- Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United States of America
| | - Alexander Ostrovsky
- Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, United States of America
| | - Han Mei
- Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United States of America
| | - Anton Nekrutenko
- Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United States of America
| | - Darren P. Martin
- Division of Computational Biology, Department of Integrative Biomedical Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Sergei L. Kosakovsky Pond
- Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
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Haddad F, Dokmak G, Karaman R. A Comprehensive Review on the Efficacy of Several Pharmacologic Agents for the Treatment of COVID-19. Life (Basel) 2022; 12:1758. [PMID: 36362912 PMCID: PMC9692303 DOI: 10.3390/life12111758] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/15/2022] [Accepted: 10/26/2022] [Indexed: 11/06/2022] Open
Abstract
SARS-CoV-2, the coronavirus disease-2019 (COVID-19), and the cause of the pandemic is extremely contagious among people and has spread around the world. Antivirals, immunomodulators, and other medications, such as antibiotics, stem cells, and plasma therapy, have all been utilized in the treatment of COVID-19. To better understand the clinical efficacy of these agents and to aid in the selection of effective COVID-19 therapies in various countries, this study reviewed the effectiveness of the various pharmacologic agents that have been used for COVID-19 therapy globally by summarizing the clinical outcomes that have been obtained from the clinical trials published on each drug related to COVID-19 infection. The Food and Drug Administration (FDA) has authorized the use of remdesivir, paxlovid, molnupiravir, baricitinib, tixagevimab-cilgavimab, and bebtelovimab for the management of COVID-19. On the other hand, most research advises against using chloroquine and hydroxychloroquine to treat COVID-19 patients because they are not beneficial. Although the FDA has given emergency use authorization for some monoclonal antibodies, including bamlanivimab, etesevimab, casirivimab, and imdevimab for managing COVID-19, they are not currently approved for use because the Omicron variant has significantly reduced their in vitro susceptibility. In this study, we also included a wide range of alternative therapy strategies that effectively treat COVID-19 patients, although further randomized studies are necessary to support and assess their applicability.
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Affiliation(s)
- Fatma Haddad
- Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Jerusalem 9103401, Palestine
- Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
| | - Ghadeer Dokmak
- Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Jerusalem 9103401, Palestine
| | - Rafik Karaman
- Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Jerusalem 9103401, Palestine
- Department of Sciences, University of Basilicata, 85100 Potenza, Italy
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Rahmasari R, Raekiansyah M, Azallea SN, Nethania M, Bilqisthy N, Rozaliyani A, Bowolaksono A, Sauriasari R. Low-cost SYBR Green-based RT-qPCR assay for detecting SARS-CoV-2 in an Indonesian setting using WHO-recommended primers. Heliyon 2022; 8:e11130. [PMCID: PMC9617658 DOI: 10.1016/j.heliyon.2022.e11130] [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: 10/24/2021] [Revised: 01/22/2022] [Accepted: 10/12/2022] [Indexed: 11/05/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the ongoing coronavirus disease 2019 (COVID-19) pandemic. For laboratory diagnosis, low-cost detection of SARS-CoV-2 is urgently needed, particularly in developing countries with limited resources. Probe- or TaqMan-based real-time reverse transcription polymerase chain reaction (RT-qPCR) is currently the gold standard for diagnosing infected individuals, as recommended by the World Health Organization (WHO). However, this assay is expensive, making it difficult to use for diagnosis on a large scale. Therefore, in this study, we develop and validate an alternative approach for RT-qPCR diagnosis by employing the DNA intercalating dye SYBR Green. We evaluate and use two WHO-recommended primers, namely CCDC-N and HKU-ORF1b-nsp14. The compatibility of the two primers was tested in silico with Indonesian SARS-CoV-2 genome sequences retrieved from the GISAID database and using bioinformatic tools. Using in vitro-transcribed RNA, optimization, sensitivity, and linearity of the two assays targeting the N and Nsp-14 genes were carried out. For further evaluation, we used clinical samples from patients and performed the SYBR Green-based RT-qPCR assay protocol in parallel with TaqMan-based commercial assay. Our results show that our methodology performs similarly to the broadly used TaqMan-based detection method in terms of specificity and sensitivity and thus offers an alternative assay for the detection of SARS-CoV-2 RNA for diagnostic purposes.
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Affiliation(s)
- Ratika Rahmasari
- Microbiology and Biotechnology Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
| | | | - Syifa Naura Azallea
- Microbiology and Biotechnology Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
| | - Marvella Nethania
- Microbiology and Biotechnology Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
| | - Navany Bilqisthy
- Microbiology and Biotechnology Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
| | - Anna Rozaliyani
- Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, West Java, Indonesia
| | - Anom Bowolaksono
- Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok 16424, West Java, Indonesia
| | - Rani Sauriasari
- Clinical Pharmacy Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia,Corresponding author
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Plant Molecular Pharming and Plant-Derived Compounds towards Generation of Vaccines and Therapeutics against Coronaviruses. Vaccines (Basel) 2022; 10:vaccines10111805. [DOI: 10.3390/vaccines10111805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/14/2022] [Accepted: 10/19/2022] [Indexed: 11/17/2022] Open
Abstract
The current century has witnessed infections of pandemic proportions caused by Coronaviruses (CoV) including severe acute respiratory syndrome-related CoV (SARS-CoV), Middle East respiratory syndrome-related CoV (MERS-CoV) and the recently identified SARS-CoV2. Significantly, the SARS-CoV2 outbreak, declared a pandemic in early 2020, has wreaked devastation and imposed intense pressure on medical establishments world-wide in a short time period by spreading at a rapid pace, resulting in high morbidity and mortality. Therefore, there is a compelling need to combat and contain the CoV infections. The current review addresses the unique features of the molecular virology of major Coronaviruses that may be tractable towards antiviral targeting and design of novel preventative and therapeutic intervention strategies. Plant-derived vaccines, in particular oral vaccines, afford safer, effectual and low-cost avenues to develop antivirals and fast response vaccines, requiring minimal infrastructure and trained personnel for vaccine administration in developing countries. This review article discusses recent developments in the generation of plant-based vaccines, therapeutic/drug molecules, monoclonal antibodies and phytochemicals to preclude and combat infections caused by SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Efficacious plant-derived antivirals could contribute significantly to combating emerging and re-emerging pathogenic CoV infections and help stem the tide of any future pandemics.
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Spoto S, Mangiacapra F, D’Avanzo G, Lemme D, Bustos Guillén C, Abbate A, Markley JD, Sambuco F, Markley R, Fogolari M, Locorriere L, Lupoi DM, Battifoglia G, Costantino S, Ciccozzi M, Angeletti S. Synergistic effect of myocardial injury and mid-regional proAdrenomedullin elevation in determining clinical outcomes of SARS-CoV-2 patients. Front Med (Lausanne) 2022; 9:929408. [PMID: 36388948 PMCID: PMC9643355 DOI: 10.3389/fmed.2022.929408] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 09/16/2022] [Indexed: 07/30/2023] Open
Abstract
OBJECTIVE Coronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients. MATERIALS AND METHODS All patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS). RESULTS A total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87-21.30; p < 0.001). CONCLUSION The study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.
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Affiliation(s)
- Silvia Spoto
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - Fabio Mangiacapra
- Unit of Cardiovascular Science, University Campus Bio-Medico of Rome, Rome, Italy
| | - Giorgio D’Avanzo
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - Daniela Lemme
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - César Bustos Guillén
- Division of Infectious Diseases, Department of Internal Medicine, Clinica Universidad de los Andes, Santiago Metropolitan, Chile
| | - Antonio Abbate
- Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United States
| | - John Daniel Markley
- Division of Infectious Disease and Epidemiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States
- Central Virginia, Veterans Administration Hospital, Richmond, VA, United States
| | - Federica Sambuco
- Department of Emergency, University Campus Bio-Medico of Rome, Rome, Italy
| | - Roshanak Markley
- Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, United States
| | - Marta Fogolari
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
- Labotarory Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Luciana Locorriere
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - Domenica Marika Lupoi
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - Giulia Battifoglia
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - Sebastiano Costantino
- Department of Diagnostic and Therapeutic Medicine, University Campus Bio-Medico of Rome, Rome, Italy
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
- Labotarory Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
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Liu T, Tian Y, Zheng A, Cui C. Design Strategies for and Stability of mRNA-Lipid Nanoparticle COVID-19 Vaccines. Polymers (Basel) 2022; 14:4195. [PMID: 36236141 PMCID: PMC9572882 DOI: 10.3390/polym14194195] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/26/2022] [Accepted: 09/27/2022] [Indexed: 11/25/2022] Open
Abstract
Messenger RNA (mRNA) vaccines have shown great preventive potential in response to the novel coronavirus (COVID-19) pandemic. The lipid nanoparticle (LNP), as a non-viral vector with good safety and potency factors, is applied to mRNA delivery in the clinic. Among the recently FDA-approved SARS-CoV-2 mRNA vaccines, lipid-based nanoparticles have been shown to be well-suited to antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses. However, a design strategy for optimal mRNA-LNP vaccines has not been fully elaborated. In this review, we comprehensively and systematically discuss the research strategies for mRNA-LNP vaccines against COVID-19, including antigen and lipid carrier selection, vaccine preparation, quality control, and stability. Meanwhile, we also discuss the potential development directions for mRNA-LNP vaccines in the future. We also conduct an in-depth review of those technologies and scientific insights in regard to the mRNA-LNP field.
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Affiliation(s)
- Ting Liu
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
| | - Yang Tian
- State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China
| | - Aiping Zheng
- State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China
| | - Chunying Cui
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
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Aanand P, Angral S, Varshney S, Raj R. Incidence of Anosmia among Covid 19 patients in India. Indian J Otolaryngol Head Neck Surg 2022; 74:3427-3436. [PMID: 34099977 PMCID: PMC8173102 DOI: 10.1007/s12070-021-02641-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 05/17/2021] [Indexed: 01/08/2023] Open
Abstract
The pandemic COVID-19 has relentlessly caused havoc to human life since its outbreak in December 2019. The disease has been a challenge for all. The clinical manifestations of Covid-19 ranges from no symptoms at all to severe acute respiratory distress syndrome. Anosmia being one of the important clinical features of COVID-19 has always been overlooked by the Indian population. This formed the background for this study. Aim To identify the incidence of anosmia reported in COVID- 19 patients in India. Materials and Methods Literature search was carried out from January 2020 to March 2021 in databases like PUBMED and Google Scholar using the key words "ANOSMIA", "HYPOSMIA" and "OLFACTORY DYSFUNCTION" in conjunction with "COVID-19", "SARS-COV-2", and "CORONAVIRUS". Boolean operators were used to narrow and broaden the search. The search yielded sixteen eligible articles. Result The scrutiny of the 16 articles revealed an incidence range of anosmia from 9.2% to 82% and an average anosmia incidence rate of 30.19%. The cumulative incidence rate of anosmia in those studies where objective analysis was done is 52.2% and 16.4% for subjective analysis. Discussion The prevalence of anosmia in Indian population is found to be much lesser than that reported by European countries due to ethnicity or negligence. Objective evaluation of anosmia in COVID-19 patients increases the incidence of anosmia drastically. Hence objective evaluations such as UPIST, SNIFFING STICK test, etc. is to be promoted. This study also Emphasises the lack of common gold standard testing for olfaction like vision and hearing.
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Affiliation(s)
- Prem Aanand
- Department of Otorhinolaryngology & Head-Neck Surgery, All India Institute of Medical Sciences, Deoghar, India
| | - Sumeet Angral
- Department of Otorhinolaryngology & Head-Neck Surgery, All India Institute of Medical Sciences, Deoghar, India
| | - Saurabh Varshney
- Department of Otorhinolaryngology & Head-Neck Surgery, All India Institute of Medical Sciences, Deoghar, India
- Department of Otorhinolaryngology & Head neck Surgery, All India Institute of Medical Sciences, Deoghar, Jharkhand 814142 India
| | - Ritu Raj
- Department of General Medicine, All India Institute of Medical Sciences, Deoghar, India
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Role of Nanomaterials in COVID-19 Prevention, Diagnostics, Therapeutics, and Vaccine Development. JOURNAL OF NANOTHERANOSTICS 2022. [DOI: 10.3390/jnt3040011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Facing the deadly pandemic caused by the SARS-CoV-2 virus all over the globe, it is crucial to devote efforts to fighting and preventing this infectious virus. Nanomaterials have gained much attention after the approval of lipid nanoparticle-based COVID-19 vaccines by the United States Food and Drug Administration (USFDA). In light of increasing demands for utilizing nanomaterials in the management of COVID-19, this comprehensive review focuses on the role of nanomaterials in the prevention, diagnostics, therapeutics, and vaccine development of COVID-19. First, we highlight the variety of nanomaterials usage in the prevention of COVID-19. We discuss the advantages of nanomaterials as well as their uses in the production of diagnostic tools and treatment methods. Finally, we review the role of nanomaterials in COVID-19 vaccine development. This review offers direction for creating products based on nanomaterials to combat COVID-19.
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Ho SM, Liu X, Seraj MS, Dickey S. Social distance "nudge:" a context aware mHealth intervention in response to COVID pandemics. COMPUTATIONAL AND MATHEMATICAL ORGANIZATION THEORY 2022; 29:1-24. [PMID: 36106126 PMCID: PMC9461402 DOI: 10.1007/s10588-022-09365-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/17/2022] [Indexed: 06/15/2023]
Abstract
The impact of the COVID pandemic to our society is unprecedented in our time. As coronavirus mutates, maintaining social distance remains an essential step in defending personal as well as public health. This study conceptualizes the social distance "nudge" and explores the efficacy of mHealth digital intervention, while developing and validating a choice architecture that aims to influence users' behavior in maintaining social distance for their own self-interest. End-user nudging experiments were conducted via a mobile phone app that was developed as a research artifact. The accuracy of social distance nudging was validated in both United States and Japan. Future work will consider behavioral studies to better understand the effectiveness of this digital nudging intervention.
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Affiliation(s)
- Shuyuan Mary Ho
- School of Information, Florida State University, 142 Collegiate Loop, P.O. Box 3062100, Tallahassee, FL 32306-2100 USA
| | - Xiuwen Liu
- Department of Computer Science, Florida State University, 1017 Academy Way, Tallahassee, FL 32304 USA
| | - Md Shamim Seraj
- Department of Computer Science, Florida State University, 1017 Academy Way, Tallahassee, FL 32304 USA
| | - Sabrina Dickey
- College of Nursing, Florida State University, 98 Varsity Way, Tallahassee, FL 32306-4310 USA
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Lessons from SARS-CoV, MERS-CoV, and SARS-CoV-2 Infections: What We Know So Far. CANADIAN JOURNAL OF INFECTIOUS DISEASES AND MEDICAL MICROBIOLOGY 2022; 2022:1156273. [PMID: 35992513 PMCID: PMC9391183 DOI: 10.1155/2022/1156273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 07/19/2022] [Indexed: 01/08/2023]
Abstract
Within past decades, human infections with emerging and reemerging zoonotic viral pathogens have raised the eminent public health concern. Since November 2002, three highly pathogenic and major deadly human coronaviruses of the βετα-genera (β-hCoVs), namely, severe acute respiratory distress syndrome-coronavirus (SARS-CoV), middle east respiratory syndrome-coronavirus (MERS-CoV), and SARS-CoV-2, have been globally emerged and culminated in the occurrence of SARS epidemic, MERS outbreak, and coronavirus disease 19 (COVID-19) pandemic, respectively. The global emergence and spread of these three major deadly β-hCoVs have extremely dreadful impacts on human health and become an economic burden. Unfortunately, clear specific and highly efficient medical countermeasures for these three β-hCoVs and their underlying fatal illnesses remain under development. Although they belong to the same family and share many features and convergent evolution, these three deadly β-hCoVs have some important and obvious differences. By utilizing their lessons and gaining a deeper understanding of these β-hCoVs, we can identify areas of improvement and provide preparedness plans for fighting and controlling the future reemerging human infections that might arise from them or from other potential pathogenic hCoVs. Therefore, this review summarizes the state-of-the-art information and compares the similarities and dissimilarities between SARS-CoV, MERS-CoV, and SARS-CoV-2, in terms of their evolution trait, genome organization, host cell entry mechanisms, tissue infectivity tropisms, transmission routes and contagiousness, and the clinical characteristics, laboratory features, and immunological abnormalities of their related illnesses. It also provides an overview of the emerging SARS-CoV-2 variants. Additionally, it discusses the challenges of the most proposed treatment options for SARS-CoV-2 infections.
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Gupta A, Ahmad R, Siddiqui S, Yadav K, Srivastava A, Trivedi A, Ahmad B, Khan MA, Shrivastava AK, Singh GK. Flavonol morin targets host ACE2, IMP-α, PARP-1 and viral proteins of SARS-CoV-2, SARS-CoV and MERS-CoV critical for infection and survival: a computational analysis. J Biomol Struct Dyn 2022; 40:5515-5546. [PMID: 33526003 PMCID: PMC7869441 DOI: 10.1080/07391102.2021.1871863] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/30/2020] [Indexed: 12/31/2022]
Abstract
A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-α and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Anamika Gupta
- Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
| | - Rumana Ahmad
- Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
| | - Sahabjada Siddiqui
- Department of Biotechnology, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
| | - Kusum Yadav
- Department of Biochemistry, University of Lucknow, Lucknow, UP, India
| | - Aditi Srivastava
- Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
| | - Anchal Trivedi
- Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
| | - Bilal Ahmad
- Research Cell, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
| | | | - Amit Kumar Shrivastava
- Department of Pharmacology, Universal College of Medical Sciences & Hospital, Ranigaon, Bhairahawa, Rupandehi, Nepal
| | - Girish Kumar Singh
- Department of Orthopedics, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, UP, India
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Yashvardhini N, Kumar A, Jha DK. Analysis of SARS-CoV-2 mutations in the main viral protease (NSP5) and its implications on the vaccine designing strategies. VACUNAS (ENGLISH EDITION) 2022. [PMCID: PMC9472678 DOI: 10.1016/j.vacune.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome), an etiolating agent of novel COVID-19 (coronavirus 2019) pandemic, rapidly spread worldwide, creating an unprecedented public health crisis globally. NSP5, the main viral protease, is a highly conserved protein, encoded by the genome of SARS-CoV-2 and plays an important role in the viral replication cycle. In the present study, we detected a total of 33 mutations from 675 sequences submitted from India in the month of March 2020 to April 2021. Out of 33 mutations, we selected 8 frequent mutations (K236R, N142L, K90R, A7V, L75F, C22N, H246Y and I43V) for further analysis. Subsequently, protein models were constructed, revealing significant alterations in the 3-D structure of NSP5 protein when compared to the wild type protein sequence which also altered the secondary structure of NSP5 protein. Further, we identified 9 B-cell, 10 T-cell and 6 MHC-I promising epitopes using predictive tools of immunoinformatics, out of these epitopes some were non-allergenic as well as highly immunogenic. Results of our study, however, revealed that 10 B-cell epitopes reside in the mutated region of NSP5. Additionally, hydrophobicity, physiochemical properties, toxicity and stability of NSP5 protein were estimated to demonstrate the specificity of the multiepitope candidates. Taken together, variations arising as a consequence of multiple mutations may cause alterations in the structure and function of NSP5 which generate crucial insights to better understand structural aspects of SARS-CoV-2. Our study also revealed, NSP5, a main protease, can be a potentially good target for the design and development of vaccine candidate against SARS-CoV-2.
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Ribeiro SP, Barh D, Andrade BS, José Santana Silva R, Costa-Rezende DH, Fonseca PLC, Tiwari S, Giovanetti M, Alcantara LCJ, Azevedo VA, Ghosh P, Diniz-Filho JAF, Loyola R, de Almeida MFB, Góes-Neto A. Long-term unsustainable patterns of development rather than recent deforestation caused the emergence of Orthocoronavirinae species. Environ Microbiol 2022; 24:4714-4724. [PMID: 35859337 DOI: 10.1111/1462-2920.16121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 06/22/2022] [Accepted: 06/29/2022] [Indexed: 11/28/2022]
Abstract
We investigated whether a set of phylogeographical tracked emergent events of Orthocoronavirinae were related to developed, urban and polluted environments worldwide. We explored coronavirus records in response to climate (rainfall parameters), population density, CO2 emission, Human Developmental Index (HDI) and deforestation. We contrasted environmental characteristics from regions with spillovers or encounters of wild Orthocoronavirinae against adjacent areas having best-preserved conditions. We used all complete sequenced CoVs genomes deposited in NCBI and GISAID databases until January 2021. Except for Deltacoronavirus, concentrated in Hong Kong and in birds, the other three genera were scattered all over the planet, beyond the original distribution of the subfamily, and found in humans, mammals, fishes and birds, wild or domestic. Spillovers and presence in wild animals were only reported in developed/densely populated places. We found significantly more occurrences reported in places with higher HDI, CO2 emission, or population density, along with more rainfall and more accentuated seasonality. Orthocoronavirinae occurred in areas with significantly higher human populations, CO2 emissions and deforestation rates than in adjacent locations. Intermediately disturbed ecosystems seemed more vulnerable for Orthocoronavirinae emergence than forested regions in frontiers of deforestation. Sadly, people experiencing poverty in an intensely consumerist society are the most vulnerable.
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Affiliation(s)
- Sérvio P Ribeiro
- Laboratório de Ecologia do Adoecimento & Florestas NUPEB/ICEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
| | - Debmalya Barh
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Purba Medinipur, West Bengal, India.,Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Bruno Silva Andrade
- Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia, Brazil
| | - Raner José Santana Silva
- Departamento de Ciências Biológicas (DCB), Universidade Estadual de Santa Cruz (UESC), Ilhéus, Bahia, Brazil.,Programa de Pós-Graduação em Genética e Biologia Molecular (PPGGBM), Universidade Estadual de Santa Cruz (UESC), Ilhéus, Bahia, Brazil
| | - Diogo Henrique Costa-Rezende
- Programa de Pós-Graduação em Botânica (PPGBot), Departamento de Ciências Biológicas, Universidade Estadual de Feira de Santana (UEFS), Feira de Santana, Bahia, Brazil
| | - Paula Luize Camargos Fonseca
- Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Sandeep Tiwari
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Marta Giovanetti
- Laboratório de Genética Celular e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.,Laboratório de Flavivírus, Instituto Oswaldo Cruz Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luiz Carlos Junior Alcantara
- Laboratório de Genética Celular e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.,Laboratório de Flavivírus, Instituto Oswaldo Cruz Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vasco Ariston Azevedo
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Preetam Ghosh
- Virginia Commonwealth University, Richmond, Virginia, USA
| | | | - Rafael Loyola
- Departamento de Ecologia, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.,Fundação Brasileira para o Desenvolvimento Sustentável, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria Fernanda Brito de Almeida
- Laboratório de Ecologia do Adoecimento & Florestas NUPEB/ICEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.,Programa de Pós-Graduação em Ecologia, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Aristóteles Góes-Neto
- Laboratório de Biologia Molecular e Computacional de Fungos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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Schindell BG, Allardice M, McBride JA, Dennehy B, Kindrachuk J. SARS-CoV-2 and the Missing Link of Intermediate Hosts in Viral Emergence - What We Can Learn From Other Betacoronaviruses. FRONTIERS IN VIROLOGY 2022; 2. [DOI: 10.3389/fviro.2022.875213] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
The emergence of SARS-CoV-2 in 2019 has resulted in a global pandemic with devastating human health and economic consequences. The development of multiple vaccines, antivirals and supportive care modalities have aided in our efforts to gain control of the pandemic. However, the emergence of multiple variants of concern and spillover into numerous nonhuman animal species could protract the pandemic. Further, these events also increase the difficulty in simultaneously monitoring viral evolution across multiple species and predicting future spillback potential into the human population. Here, we provide historic context regarding the roles of reservoir and intermediate hosts in coronavirus circulation and discuss current knowledge of these for SARS-CoV-2. Increased understanding of SARS-CoV-2 zoonoses are fundamental for efforts to control the global health and economic impacts of COVID-19.
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Santos AP, Gonçalves LC, Oliveira ACC, Queiroz PHP, Ito CRM, Santos MO, Carneiro LC. Bacterial Co-Infection in Patients with COVID-19 Hospitalized (ICU and Not ICU): Review and Meta-Analysis. Antibiotics (Basel) 2022; 11:antibiotics11070894. [PMID: 35884147 PMCID: PMC9312179 DOI: 10.3390/antibiotics11070894] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/14/2022] [Accepted: 06/22/2022] [Indexed: 01/27/2023] Open
Abstract
The prevalence of patients hospitalized in ICUs with COVID-19 and co-infected by pathogenic bacteria is relevant in this study, considering the integrality of treatment. This systematic review assesses the prevalence of co-infection in patients admitted to ICUs with SARS-CoV-2 infection, using the PRISMA guidelines. We examined the results of the PubMed, Embase, and SciELO databases, searching for published English literature from December 2019 to December 2021. A total of 542 rec ords were identified, but only 38 were eligible and, and of these only 10 were included. The tabulated studies represented a sample group of 1394 co-infected patients. In total, 35%/138 of the patients were co-infected with Enterobacter spp., 27% (17/63) were co-infected with methicillin-sensitive Staphylococ cus aureus, 21% (84/404) were co-infected with Klebsiella spp., 16% (47/678) of patients were co-infected with coagulase-negative Staphylococcus, 13% (10/80) co-infected with Escherichia coli (ESBL), and 3% (30/1030) of patients were co-infected with Pseudomonas aeruginosa. The most common co-infections were related to blood flow; although in the urinary and respiratory tracts of patients Streptococcus pneumoniae was found in 57% (12/21) of patients, coagulase negative Staphylococcus in 44% (7/16) of patients, and Escherichia coli was found in 37% (11/29) of patients. The present research demonstrated that co-infections caused by bacteria in patients with COVID-19 are a concern.
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Affiliation(s)
- Adailton P. Santos
- Medicine College, Federal University of Goiás, 235 Street, Goiânia 74690-900, Brazil; (A.P.S.); (L.C.G.); (A.C.C.O.); (P.H.P.Q.); (M.O.S.)
| | - Lucas C. Gonçalves
- Medicine College, Federal University of Goiás, 235 Street, Goiânia 74690-900, Brazil; (A.P.S.); (L.C.G.); (A.C.C.O.); (P.H.P.Q.); (M.O.S.)
| | - Ana C. C. Oliveira
- Medicine College, Federal University of Goiás, 235 Street, Goiânia 74690-900, Brazil; (A.P.S.); (L.C.G.); (A.C.C.O.); (P.H.P.Q.); (M.O.S.)
| | - Pedro H. P. Queiroz
- Medicine College, Federal University of Goiás, 235 Street, Goiânia 74690-900, Brazil; (A.P.S.); (L.C.G.); (A.C.C.O.); (P.H.P.Q.); (M.O.S.)
| | - Célia R. M. Ito
- Institute of Tropical Pathology and Public Health, Federal University of Goiás, 235 Street, Goiânia 74605-050, Brazil;
| | - Mônica O. Santos
- Medicine College, Federal University of Goiás, 235 Street, Goiânia 74690-900, Brazil; (A.P.S.); (L.C.G.); (A.C.C.O.); (P.H.P.Q.); (M.O.S.)
| | - Lilian C. Carneiro
- Institute of Tropical Pathology and Public Health, Federal University of Goiás, 235 Street, Goiânia 74605-050, Brazil;
- Correspondence: ; Tel.: +55-(62)-32096528
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Mishra AR, Nayak D, Byrareddy SN. Are we moving toward ending SARS-CoV-2? J Med Virol 2022; 94:2921-2924. [PMID: 35288953 PMCID: PMC9088646 DOI: 10.1002/jmv.27722] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/16/2022] [Accepted: 03/12/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Anurag R. Mishra
- Discipline of Biosciences and Biomedical EngineeringIndian Institute of Technology IndoreIndoreMadhya PradeshIndia
| | - Debasis Nayak
- Department of Biological SciencesIndian Institute of Science Education and ResearchBhopalMadhya PradeshIndia
| | - Siddappa N. Byrareddy
- Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaNebraskaUSA
- Department of Genetics, Cell Biology and AnatomyUniversity of Nebraska Medical CenterOmahaNebraskaUSA
- Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaNebraskaUSA
- Division of Clinical Microbiology, Department of Laboratory MedicineKarolinska InstituteStockholmSweden
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46
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Hadj Hassine I. Covid-19 vaccines and variants of concern: A review. Rev Med Virol 2022; 32:e2313. [PMID: 34755408 PMCID: PMC8646685 DOI: 10.1002/rmv.2313] [Citation(s) in RCA: 199] [Impact Index Per Article: 66.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 10/25/2021] [Accepted: 10/25/2021] [Indexed: 12/20/2022]
Abstract
Since the outbreak of coronavirus disease 2019 (Covid-19) in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of confirmed infections has risen to more than 242 million worldwide, with nearly 5 million deaths. Currently, nine Covid-19 vaccine candidates based on the original Wuhan-Hu-1 strain are at the forefront of vaccine research. All nine had an efficacy over 50% against symptomatic Covid-19 disease: NVX-CoV2373 (∼96%), BNT162b2 (∼95%), mRNA-1273 (∼94%), Sputnik V (∼92%), AZD1222 (∼81%), BBIBP-CorV (∼79%), Covaxin (∼78%), Ad26.CoV.S (∼66%) and CoronaVac (∼51%). However, vaccine efficacy (VE) can be jeopardised by the rapid emergence and spread of SARS-CoV-2 variants of concern (VOCs) that could escape from neutralising antibodies and/or cell-mediated immunity. Rare adverse events have also been reported soon after administration of viral vector and mRNA vaccines. Although many Covid-19 vaccines have been developed, additional effective vaccines are still needed to meet the global demand. Promising Covid-19 vaccines such as WIBP-CorV, AD5-nCOV, ZyCoV-D, CVnCoV, EpiVacCorona and ZF2001 have advanced to clinical studies. This review describes the most relevant mutations in the SARS-CoV-2 spike protein, discusses VE against VOCs, presents rare adverse events after Covid-19 vaccination and introduces some promising Covid-19 vaccine candidates.
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Affiliation(s)
- Ikbel Hadj Hassine
- Unité de Recherche UR17ES30 ‘Génomique, Biotechnologie et Stratégies Antivirales‘Institut Supérieur de Biotechnologie, Université de MonastirMonastirTunisia
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RNA enigma: "From origin of life to novel Coronavirus- COVID-19". Saudi J Biol Sci 2022; 29:103331. [PMID: 35668729 PMCID: PMC9158322 DOI: 10.1016/j.sjbs.2022.103331] [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: 10/11/2021] [Revised: 04/21/2022] [Accepted: 05/29/2022] [Indexed: 11/29/2022] Open
Abstract
Recent events of the viral catastrophe have shown the rapidity of spread of new disease through emergence of virulent strains. Proper control measures can be developed only through understanding the evolution of virulence in RNA viruses. To understand the evolution of this novel Coronavirus, COVID-19, it is imperative to delineate the evolution of RNA, its transformation into first life forms, the steady and continuous evolution and emergence through modification in their genome and nevertheless the natural selection. This review will throw light on these aspects to understand the possible origin of COVID-19 to control and eradicate this viral outbreak.
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Ylikoski J, Lehtimäki J, Pääkkönen R, Mäkitie A. Prevention and Treatment of Life-Threatening COVID-19 May Be Possible with Oxygen Treatment. Life (Basel) 2022; 12:754. [PMID: 35629421 PMCID: PMC9142938 DOI: 10.3390/life12050754] [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: 03/19/2022] [Revised: 04/22/2022] [Accepted: 05/12/2022] [Indexed: 01/08/2023] Open
Abstract
Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory distress. These symptoms suggest hypoxia, specifically affecting the brain. The condition is best explained by primary replication of the virus in the nasal respiratory and/or the olfactory epithelia, followed by an invasion of the virus into the central nervous system, including the respiratory centers, either along a transneural route, through disruption of the blood-brain barrier, or both. In patients, presenting with early dyspnea, the primary goal of therapy should be the reversal of brain hypoxia as efficiently as possible. The first approach should be intermittent treatment with 100% oxygen using a tight oronasal mask or a hood. If this does not help within a few hours, an enclosure is needed to increase the ambient pressure. This management approach is well established in the hypoxia-related diseases in diving and aerospace medicine and preserves the patient's spontaneous breathing. Preliminary research evidence indicates that even a small elevation of the ambient pressure might be lifesaving. Other neurological symptoms, presenting particularly in long COVID-19, suggest imbalance of the autonomous nervous system, i.e., dysautonomia. These patients could benefit from vagal nerve stimulation.
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Affiliation(s)
- Jukka Ylikoski
- Department of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland; (J.Y.); (R.P.)
- Helsinki Ear Institute, 00420 Helsinki, Finland;
- Salustim Group Inc., 90440 Kempele, Finland
| | - Jarmo Lehtimäki
- Helsinki Ear Institute, 00420 Helsinki, Finland;
- Salustim Group Inc., 90440 Kempele, Finland
| | - Rauno Pääkkönen
- Department of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland; (J.Y.); (R.P.)
| | - Antti Mäkitie
- Department of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland; (J.Y.); (R.P.)
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Kashyap D, Roy R, Kar P, Jha HC. Plant-derived active compounds as a potential nucleocapsid protein inhibitor of SARS-CoV-2: an in-silico study. J Biomol Struct Dyn 2022:1-16. [PMID: 35532092 DOI: 10.1080/07391102.2022.2072951] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. This virus has a high mismatch repair proofreading ability due to its unique exonuclease activity, making it knotty to treat. The nucleocapsid protein can serve as a potential antiviral drug target, as this protein is responsible for multiple captious functions during the viral life cycle. Herein, we have investigated the potential to repurpose active antiviral compounds of plant origins for treating the SARS-CoV-2 infection. In the present study, we followed the molecular docking methodology to screen druggable natural plants' active compounds against the nucleocapsid protein of SARS-CoV-2. The virtual screening of all 68 compounds revealed that the top seven active compounds, such as withanolide D, hypericin, silymarin, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein, exhibit good binding affinity with druggable ADME properties, toxicity, and Pass prediction. The stability of the docked complexes was studied by conducting molecular simulations of 100 ns. MM-GBSA calculated the binding free energy uncovered that withanolide D, hypericin, and silymarin result in highly stable binding conformations in three different sites of the nucleocapsid protein. However, further investigation is needed in order to validate the candidacy of these inhibitors for clinical trials. HighlightsNatural plants' active compounds may aid in the inhibition of SARS-CoV-2 replication and COVID-19 therapeutics.Hypericin, silymarin, withanolide D, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein are effective against SARS-CoV-2 N protein.Studied natural plants' active compounds could be useful against COVID-19 and its associated organs comorbidities.ADMET properties of selected compounds favor these compounds as druggable candidates.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Dharmendra Kashyap
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, Madhya Pradesh, India
| | - Rajarshi Roy
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, Madhya Pradesh, India
| | - Parimal Kar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, Madhya Pradesh, India
| | - Hem Chandra Jha
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, Madhya Pradesh, India
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Yashvardhini N, Kumar A, Jha DK. Analysis of SARS-CoV-2 mutations in the main viral protease (NSP5) and its implications on the vaccine designing strategies. VACUNAS 2022; 23:S1-S13. [PMID: 34876891 PMCID: PMC8639442 DOI: 10.1016/j.vacun.2021.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 10/26/2021] [Indexed: 12/14/2022]
Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome), an etiolating agent of novel COVID-19 (coronavirus 2019) pandemic, rapidly spread worldwide, creating an unprecedented public health crisis globally. NSP5, the main viral protease, is a highly conserved protein, encoded by the genome of SARS-CoV-2 and plays an important role in the viral replication cycle. In the present study, we detected a total of 33 mutations from 675 sequences submitted from India in the month of March 2020 to April 2021. Out of 33 mutations, we selected 8 frequent mutations (K236R, N142L, K90R, A7V, L75F, C22N, H246Y and I43V) for further analysis. Subsequently, protein models were constructed, revealing significant alterations in the 3-D structure of NSP5 protein when compared to the wild type protein sequence which also altered the secondary structure of NSP5 protein. Further, we identified 9 B-cell, 10 T-cell and 6 MHC-I promising epitopes using predictive tools of immunoinformatics, out of these epitopes some were non-allergenic as well as highly immunogenic. Results of our study, however, revealed that 10 B-cell epitopes reside in the mutated region of NSP5. Additionally, hydrophobicity, physiochemical properties, toxicity and stability of NSP5 protein were estimated to demonstrate the specificity of the multiepitope candidates. Taken together, variations arising as a consequence of multiple mutations may cause alterations in the structure and function of NSP5 which generate crucial insights to better understand structural aspects of SARS-CoV-2. Our study also revealed, NSP5, a main protease, can be a potentially good target for the design and development of vaccine candidate against SARS-CoV-2.
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Affiliation(s)
- Niti Yashvardhini
- Department of Microbiology, Patna Women's College, Patna 800 001, India
| | - Amit Kumar
- Department of Botany, Patna University, Patna 800 005, India
| | - Deepak Kumar Jha
- Department of Zoology, P. C. Vigyan Mahavidyalaya, J. P. University, Chapra 841 301, India
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