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Ruchisrisarod C, Wanthong P, Joyjinda Y, Bunprakob S, Hemachudha P, Mungaomklang A, Supharatpariyakorn T, Hemachudha T, Wasontiwong AS. Antibodies response in symptomatic and asymptomatic SARS-CoV-2 infected persons in Thailand. PLoS One 2025; 20:e0308850. [PMID: 39932922 PMCID: PMC11813072 DOI: 10.1371/journal.pone.0308850] [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: 10/19/2023] [Accepted: 07/31/2024] [Indexed: 02/13/2025] Open
Abstract
Antibody assays of IgM, IgG and surrogate isotype independent virus neutralizing antibody (sVNT) targeting receptor binding domain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were employed in 97 real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed Coronavirus Disease 2019 (COVID-19) patients with varying severity admitted to King Chulalongkorn Memorial Hospital. Concordance rate was 100% regardless of severity, onset of symptoms and magnitude of viral load. Per available samples, antibodies appeared on the same day of symptom onset in one patient; one day after in 18 patients and two days after in 19 patients. In two patients, antibodies appeared as early as 4 days after infection (exposure). IgM and IgG were evident in all patients' first assay (within two days of admission). sVNT was also evident within two days of admission in all but 3 patients. IgM usually remained positive during the entire course of hospital stay, where the longest in this study was 32 days. Antibody assays were also applied to samples collected at a State Quarantine premise from 77 asymptomatic Thais returning from Sudan in October. Virus was detected by real-time RT-PCR in 15 cases (day 0 = 6, day 3 = 4, day 5 = 4 and day 9 = 1). Twenty-nine (including 11 RT-PCR positive cases) were antibody positive on day 0, while 4 PCR positive with antibody negative on day 0 became antibody positive on day 14. Evaluation on antibody response at days 7 or 10 is needed to help build a case to shorten length of quarantine among negative cases.
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Affiliation(s)
- Chanida Ruchisrisarod
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Phanni Wanthong
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yutthana Joyjinda
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Saowalak Bunprakob
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pasin Hemachudha
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Anek Mungaomklang
- Department of Disease Control, Ministry of Public Health, Institute for Urban Disease Control and Prevention, Bangkok, Thailand
| | - Thirawat Supharatpariyakorn
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thiravat Hemachudha
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Abhinbhen Saraya Wasontiwong
- Thai Red Cross Emerging Infectious Diseases Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Barbon S, Armellin F, Passerini V, De Angeli S, Primerano S, Del Pup L, Durante E, Macchi V, De Caro R, Parnigotto PP, Veronesi A, Porzionato A. Innate immune response in COVID-19: single-cell multi-omics profile of NK lymphocytes in a clinical case series. Cell Commun Signal 2024; 22:496. [PMID: 39407208 PMCID: PMC11476714 DOI: 10.1186/s12964-024-01867-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) represents the biggest global health emergency in recent decades. The host immune response to SARS-CoV-2 seems to play a key role in disease pathogenesis and clinical manifestations, with Natural Killer (NK) lymphocytes being among the targets of virus-induced regulation. METHODS This study performed a single-cell multi-omics analysis of transcripts and proteins of NK lymphocytes in COVID-19 patients, for the characterization of the innate immunological response to infection. NK cells were isolated from peripheral blood samples collected from adult subjects divided into 3 study groups: (1) non-infected subjects (Naïve group, n = 3), (2) post COVID-19 convalescent subjects (Healed group, n = 3) and (3) patients that were vaccinated against SARS-CoV-2 (Vaccine group, n = 3). Cells were then analysed by the BD Rhapsody System for the single-cell multi-omics investigation of transcriptome and membrane proteins. RESULTS The bioinformatic analysis identified 5 cell clusters which differentially expressed gene/protein markers, defining NK cell subsets as "Active NK cells" and "Mature NK cells". Calculating the relative proportion of each cluster within patient groups, more than 40% of the Naïve group cell population was found to belong to Mature NKs, whereas more than 75% of the Vaccine group cell population belonged to the cluster of Active NKs. Regarding the Healed group, it seemed to show intermediate phenotype between Active and Mature NK cells. Differential expression of specific genes, proteins and signaling pathways was detected comparing the profile of the 3 experimental groups, revealing a more activated NK cell phenotype in vaccinated patients versus recovered individuals. CONCLUSIONS The present study detected differential expression of NK cell markers in relation to SARS-CoV-2 infection and vaccine administration, suggesting the possibility to identify key molecular targets for clinical-diagnostic use of the individual response to viral infection and/or re-infection.
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Affiliation(s)
- Silvia Barbon
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy.
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy.
| | - Fabrizio Armellin
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Verena Passerini
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
| | - Sergio De Angeli
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Simona Primerano
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Laura Del Pup
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Elisabetta Durante
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Veronica Macchi
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy
| | - Raffaele De Caro
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
| | - Pier Paolo Parnigotto
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
| | - Arianna Veronesi
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy.
| | - Andrea Porzionato
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
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Cin D, Soguksu P, Oren MM, Ozgulnar N, Agacfidan A, Mese S. The Anti-SARS-CoV-2 S-Protein IgG, Which Is Detected Using the Chemiluminescence Microparticle Immunoassay (CMIA) in Individuals Having Either a History of COVID-19 Vaccination and/or SARS-CoV-2 Infection, Showed a High-Titer Neutralizing Effect. Viruses 2024; 16:1409. [PMID: 39339885 PMCID: PMC11437471 DOI: 10.3390/v16091409] [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: 06/11/2024] [Revised: 08/07/2024] [Accepted: 08/27/2024] [Indexed: 09/30/2024] Open
Abstract
Neutralizing antibodies plays a primary role in protective immunity by preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from entering the cells. Therefore, characterization of antiviral immunity is important for protection against SARS-CoV-2. In this study, the neutralizing effect of the anti-SARS-CoV-2 S1 protein IgG, which was detected using the chemiluminescence microparticle immunoassay (CMIA)-based SARS-CoV-2 IgG II Quant (Abbott, Waukegan, IL, USA) test in SARS-CoV-2 infected and/or vaccinated individuals, was investigated with a surrogate virus neutralization test (sVNT). In total, 120 Seropositive individuals were included in this study. They were divided into two groups: Vaccinated (n = 60) and Vaccinated + Previously Infected (n = 60). A commercial sVNT, the ACE2-RBD Neutralization Test (Dia.Pro, Milan, Italy), was used to assess the neutralizing effect. The assay is performed in two steps: screening and titration. The screening showed positive results in all seropositive samples. Low titration in 1.7%, medium titration in 5%, and high titration in 93.3% of the Vaccinated group, and medium titration in 1.7% and high titration in 98.3% of the other group, as obtained from the ACE2-RBD titration test. A strong positive and significant correlation was found between the SARS-CoV-2 IgG II Quant test and the ACE2-RBD titration test at the 1/32 titration level for both groups (p < 0.001 for both). This study shows that the SARS-CoV-2 IgG detected using the CMIA method after SARS-CoV-2 infection and/or vaccination has a high neutralizing titration by using the sVNT. In line with these data, knowledge that seropositivity determined by CMIA also indicates a strong neutralizing effect contributes to countrywide planning for protecting the population.
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Affiliation(s)
- Dilan Cin
- Department of Medical Microbiology, Istanbul Medicine Faculty, Istanbul University, 34093 Istanbul, Turkey
- Institute of Health Sciences, Istanbul University, 34126 Istanbul, Turkey
| | - Pinar Soguksu
- Department of Medical Microbiology, Istanbul Medicine Faculty, Istanbul University, 34093 Istanbul, Turkey
| | - Meryem Merve Oren
- Department of Public Health, Istanbul Medicine Faculty, Istanbul University, 34093 Istanbul, Turkey
| | - Nuray Ozgulnar
- Department of Public Health, Istanbul Medicine Faculty, Istanbul University, 34093 Istanbul, Turkey
| | - Ali Agacfidan
- Department of Medical Microbiology, Istanbul Medicine Faculty, Istanbul University, 34093 Istanbul, Turkey
| | - Sevim Mese
- Department of Medical Microbiology, Istanbul Medicine Faculty, Istanbul University, 34093 Istanbul, Turkey
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4
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Popadyuk EE, Sizikova TE, Khmelev AL, Timofeev MA, Lebedev VN, Borisevich SV. [The use of immunoglobulins and monoclonal antibodies against COVID-19]. Vopr Virusol 2024; 69:119-126. [PMID: 38843018 DOI: 10.36233/0507-4088-225] [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: 02/07/2024] [Indexed: 06/14/2024]
Abstract
INTRODUCTION When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic. RESULTS AND CONCLUSION The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.
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Affiliation(s)
- E E Popadyuk
- 48 Central Research Institute of the Ministry of Defense of the Russian Federation
| | - T E Sizikova
- 48 Central Research Institute of the Ministry of Defense of the Russian Federation
| | - A L Khmelev
- 48 Central Research Institute of the Ministry of Defense of the Russian Federation
| | - M A Timofeev
- Directorate of the Chief of the Radiation, Chemical and Biological Protection Troops of the Armed Forces of the Russian Federation
| | - V N Lebedev
- 48 Central Research Institute of the Ministry of Defense of the Russian Federation
| | - S V Borisevich
- 48 Central Research Institute of the Ministry of Defense of the Russian Federation
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5
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Kumar A, Tripathi P, Kumar P, Shekhar R, Pathak R. From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2. Vaccines (Basel) 2024; 12:459. [PMID: 38793710 PMCID: PMC11125746 DOI: 10.3390/vaccines12050459] [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: 03/13/2024] [Revised: 04/20/2024] [Accepted: 04/22/2024] [Indexed: 05/26/2024] Open
Abstract
Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale.
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Affiliation(s)
- Anoop Kumar
- Molecular Diagnostic Laboratory, National Institute of Biologicals, Noida 201309, India
| | - Prajna Tripathi
- Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA;
| | - Prashant Kumar
- R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA
| | - Ritu Shekhar
- Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Rajiv Pathak
- Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA
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Busaranuvong P, Ammartayakun A, Korkin D, Khosravi-Far R. Graph Convolutional Network for predicting secondary structure of RNA. RESEARCH SQUARE 2024:rs.3.rs-3798842. [PMID: 38464300 PMCID: PMC10925402 DOI: 10.21203/rs.3.rs-3798842/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
The prediction of RNA secondary structures is essential for understanding its underlying principles and applications in diverse fields, including molecular diagnostics and RNA-based therapeutic strategies. However, the complexity of the search space presents a challenge. This work proposes a Graph Convolutional Network (GCNfold) for predicting the RNA secondary structure. GCNfold considers an RNA sequence as graph-structured data and predicts posterior base-pairing probabilities given the prior base-pairing probabilities, calculated using McCaskill's partition function. The performance of GCNfold surpasses that of the state-of-the-art folding algorithms, as we have incorporated minimum free energy information into the richly parameterized network, enhancing its robustness in predicting non-homologous RNA secondary structures. A Symmetric Argmax Post-processing algorithm ensures that GCNfold formulates valid structures. To validate our algorithm, we applied it to the SARS-CoV-2 E gene and determined the secondary structure of the E-gene across the Betacoronavirus subgenera.
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Affiliation(s)
- Palawat Busaranuvong
- Department of Data Science, Worcester Polytechnic Institute, Worcester, 01609, Massachusetts, USA
- InnoTech Precision Medicine, Boston, 02130, Massachusetts, USA
| | - Aukkawut Ammartayakun
- Department of Data Science, Worcester Polytechnic Institute, Worcester, 01609, Massachusetts, USA
| | - Dmitry Korkin
- Department of Computer Science, Worcester Polytechnic Institute, Worcester, 01609, Massachusetts, USA
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Tong X, Deng Y, Cizmeci D, Fontana L, Carlock MA, Hanley HB, McNamara RP, Lingwood D, Ross TM, Alter G. Distinct Functional Humoral Immune Responses Are Induced after Live Attenuated and Inactivated Seasonal Influenza Vaccination. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2024; 212:24-34. [PMID: 37975667 PMCID: PMC10872955 DOI: 10.4049/jimmunol.2200956] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 10/19/2023] [Indexed: 11/19/2023]
Abstract
Influenza viruses infect 5-30% of the world's population annually, resulting in millions of incidents of hospitalization and thousands of mortalities worldwide every year. Although annual vaccination has significantly reduced hospitalization rates in vulnerable populations, the current vaccines are estimated to offer a wide range of protection from 10 to 60% annually. Such incomplete immunity may be related to both poor antigenic coverage of circulating strains, as well as to the insufficient induction of protective immunity. Beyond the role of hemagglutinin (HA) and neuraminidase (NA), vaccine-induced Abs have the capacity to induce a broader array of Ab effector functions, including Ab-dependent cellular cytotoxicity, that has been implicated in universal immunity against influenza viruses. However, whether different vaccine platforms can induce functional humoral immunity in a distinct manner remains incompletely defined. In this study, we compared vaccine-induced humoral immune responses induced by two seasonal influenza vaccines in Homo sapiens, the i.m. inactivated vaccine (IIV/Fluzone) and the live attenuated mucosal vaccine (LAIV/FluMist). Whereas the inactivated influenza vaccine induced superior Ab titers and FcγR binding capacity to diverse HA and NA Ags, the live attenuated influenza mucosal vaccine induced a more robust functional humoral immune response against both the HA and NA domains. Multivariate Ab analysis further highlighted the significantly different overall functional humoral immune profiles induced by the two vaccines, marked by differences in IgG titers, FcR binding, and both NK cell-recruiting and opsonophagocytic Ab functions. These results highlight the striking differences in Ab Fc-effector profiles induced systemically by two distinct influenza vaccine platforms.
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Affiliation(s)
- Xin Tong
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
| | - Yixiang Deng
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
| | - Deniz Cizmeci
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
| | - Laura Fontana
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
| | - Michael A. Carlock
- Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA
| | - Hannah B. Hanley
- Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA
| | | | - Daniel Lingwood
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
| | - Ted M. Ross
- Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA
- Department of Infectious Diseases, University of Georgia, Athens, GA, USA
| | - Galit Alter
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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Lee JD, Menasche BL, Mavrikaki M, Uyemura MM, Hong SM, Kozlova N, Wei J, Alfajaro MM, Filler RB, Müller A, Saxena T, Posey RR, Cheung P, Muranen T, Heng YJ, Paulo JA, Wilen CB, Slack FJ. Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53. Cell Rep 2023; 42:113478. [PMID: 37991919 PMCID: PMC10785701 DOI: 10.1016/j.celrep.2023.113478] [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: 05/17/2023] [Revised: 09/13/2023] [Accepted: 11/06/2023] [Indexed: 11/24/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.
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Affiliation(s)
- Jonathan D Lee
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
| | - Bridget L Menasche
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Maria Mavrikaki
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Madison M Uyemura
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Su Min Hong
- Department of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Nina Kozlova
- Department of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Jin Wei
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Mia M Alfajaro
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Renata B Filler
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Arne Müller
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Tanvi Saxena
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Ryan R Posey
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
| | - Priscilla Cheung
- Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Taru Muranen
- Department of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Yujing J Heng
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
| | - Joao A Paulo
- Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
| | - Craig B Wilen
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Frank J Slack
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02115, USA.
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9
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Lv Y, Huang L, Wang J, He H, Song L, He J, Xu L, Yu C, Mei Y, Gao Q. A community study of neutralizing antibodies against SARS-CoV-2 in China. Front Immunol 2023; 14:1282612. [PMID: 38143749 PMCID: PMC10748485 DOI: 10.3389/fimmu.2023.1282612] [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: 08/24/2023] [Accepted: 11/23/2023] [Indexed: 12/26/2023] Open
Abstract
Background The immune background of the overall population before and after the outbreak of SARS-CoV-2 in China remains unexplored. And the level of neutralizing antibodies is a reliable indicator of individual immunity. Objectives This study aimed to assess the immune levels of different population groups during a viral outbreak and identify the factors influencing these levels. Methods We measured the levels of neutralizing antibodies in 12,137 participants using the COVID19 Neutralizing Antibody Detection kit. The dynamics of neutralizing antibodies were analyzed using a generalized additive model, while a generalized linear model and multi-factor analysis of variance were employed to investigate the influencing factors. Additionally, statistical methods were used to compare neutralizing antibody levels among subgroups of the real-world population. Results Participants who received booster doses exhibited significantly higher levels of neutralizing antibodies compared to those who received only one or two doses (p<0.001). Both elderly [22.55 (5.12, 62.03) IU/mL, 55%] and minors [21.41 (8.15, 45.06) IU/mL, 56%] showed lower positivity rates and neutralizing antibody levels compared to young adults [29.30 (9.82, 188.08) IU/mL, 62%] (p<0.001). Furthermore, the HIV-positive group demonstrated a slightly lower seropositivity rate compared to the healthy group across the three vaccination time points. Notably, three months after the large-scale infection, both the neutralizing antibody level and positivity rate in real-world populations were higher than the previous record [300 (300, 300) IU/mL, 89%; 27.10 (8.77, 139.28) IU/mL, 60%], and this difference was statistically significant. Conclusions Increasing vaccine dosage enhances neutralizing antibody levels, resulting in greater and longer-lasting immunity. Monitoring immune levels in older individuals and those with AIDS is crucial. Additionally, the neutralizing antibodies generated from vaccination have not yet reached the threshold for achieving herd immunity, while individuals exhibit higher immune levels following a large-scale infection. These findings provide valuable insights for guiding new strategies in vaccine administration.
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Affiliation(s)
- Yitong Lv
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Lei Huang
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Junhu Wang
- Health Management Center, AnQing Municipal Hospital, Anqing, Anhui, China
| | - Hui He
- Health Management Department, Shenzhen People’s Hospital, Shenzhen, China
| | - Libo Song
- Health Examination Center, Central Hospital of Jin Zhou, Jinzhou, Liaoning, China
| | - Jia He
- Health Service Center, Shulan (Hang Zhou) Hospital, Hangzhou, Zhejiang, China
| | - Lida Xu
- Beijing Hotgen Biotech Co., Ltd, Beijing, China
| | - Changyuan Yu
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Ying Mei
- Health Management (Medical Examination) Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qi Gao
- Beijing Hotgen Biotech Co., Ltd, Beijing, China
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10
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Karagöz IK, Kaya M, Rückert R, Bozman N, Kaya V, Bayram H, Yıldırım M. A bioinformatic analysis: Previous allergen exposure may support anti- SARS-CoV-2 immune response. Comput Biol Chem 2023; 107:107961. [PMID: 37788543 DOI: 10.1016/j.compbiolchem.2023.107961] [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: 06/07/2021] [Revised: 09/17/2023] [Accepted: 09/18/2023] [Indexed: 10/05/2023]
Abstract
COVID-19, caused by infection with the SARS-CoV-2 has become a global health problem due to significant mortality rates; the exact pathophysiological mechanism remains uncertain. Articles reporting patient data are quite heterogeneous and have several limitations. Surviving patients develop a CD4 and CD8 T-cell response to the virus SARS-CoV-2 during COVID-19. Interestingly, pre-existing virus-reactive T-cells have been found in patients that were not infected before, suggesting some form of cross-reactivity or immunological mimicry. To better understand this phenomenon, we performed a bioinformatic study, which was aimed to identify antigenic structures that may explain the presence of such "reactive" T-cells, which may support or modulate the immune response to SARS-CoV-2 infections. Seven different common environmental allergen epitopes identical to the SARS-CoV-2 S-protein were identified that share affinity to 8 MHCI-specific epitope regions. Pollen showed the greatest similarity with the S protein epitope. In the epitope similarity analysis between the S protein and MHC-II / T helper epitopes, the highest similarity was determined for mites. When S-protein that stimulates B cells and identical epitope antigens are examined, the most common allergens were hornbeam and wheat. The high epitope similarity observed for the allergens examined and S protein epitopes suggest that these allergens may be a reason for pre-existing SARS-CoV-2 - reactive T-cells in previously non-infected subjects and such a previous exposure may affect the course of the disease in COVID-19 infection. It remains to be determined whether such a previous existence of SARS-CoV-2 reactive cells can support the clearance of the virus or if they, in contrast, may even aggravate the disease course. (Table 4, Ref 54).
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Affiliation(s)
- Isıl Kutluturk Karagöz
- Umraniye Trn. And Rch. Hospital, Division of Ophthalmology, Istanbul, Turkey; Yıldız Technical University, Bioengineering Department, Istanbul, Turkey.
| | | | | | - Nazli Bozman
- Gaziantep University Arts and Science Faculty Department of Biology, Gaziantep, Turkey
| | - Vildan Kaya
- Medstar Antalya Hospital, Division of Radiation Oncology, Antalya, Turkey
| | - Halim Bayram
- Dr. Ersin Arslan Trn. And Rch Hospital, Division of Infection Diseases, Gaziantep, Turkey
| | - Mustafa Yıldırım
- Sanko University, School of Medicine, Internal Diseases, Division of Oncology, Gaziantep, Turkey
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11
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Bai G, Sun C, Guo Z, Wang Y, Zeng X, Su Y, Zhao Q, Ma B. Accelerating antibody discovery and design with artificial intelligence: Recent advances and prospects. Semin Cancer Biol 2023; 95:13-24. [PMID: 37355214 DOI: 10.1016/j.semcancer.2023.06.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 06/09/2023] [Accepted: 06/18/2023] [Indexed: 06/26/2023]
Abstract
Therapeutic antibodies are the largest class of biotherapeutics and have been successful in treating human diseases. However, the design and discovery of antibody drugs remains challenging and time-consuming. Recently, artificial intelligence technology has had an incredible impact on antibody design and discovery, resulting in significant advances in antibody discovery, optimization, and developability. This review summarizes major machine learning (ML) methods and their applications for computational predictors of antibody structure and antigen interface/interaction, as well as the evaluation of antibody developability. Additionally, this review addresses the current status of ML-based therapeutic antibodies under preclinical and clinical phases. While many challenges remain, ML may offer a new therapeutic option for the future direction of fully computational antibody design.
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Affiliation(s)
- Ganggang Bai
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Chuance Sun
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ziang Guo
- Cancer Center, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao Special Administrative Region of China
| | - Yangjing Wang
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xincheng Zeng
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yuhong Su
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qi Zhao
- Cancer Center, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao Special Administrative Region of China; MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao Special Administrative Region of China.
| | - Buyong Ma
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Digiwiser BioTechnolgy, Limited, Shanghai 201203, China.
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12
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Lee JD, Menasche BL, Mavrikaki M, Uyemura MM, Hong SM, Kozlova N, Wei J, Alfajaro MM, Filler RB, Müller A, Saxena T, Posey RR, Cheung P, Muranen T, Heng YJ, Paulo JA, Wilen CB, Slack FJ. Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.31.555625. [PMID: 37693555 PMCID: PMC10491142 DOI: 10.1101/2023.08.31.555625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
COVID-19 remains a significant public health threat due to the ability of SARS-CoV-2 variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and MERS-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here we used our recently developed integrative DNA And Protein Tagging (iDAPT) methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.
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13
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Zeng X, Bai G, Sun C, Ma B. Recent Progress in Antibody Epitope Prediction. Antibodies (Basel) 2023; 12:52. [PMID: 37606436 PMCID: PMC10443277 DOI: 10.3390/antib12030052] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/31/2023] [Accepted: 08/03/2023] [Indexed: 08/23/2023] Open
Abstract
Recent progress in epitope prediction has shown promising results in the development of vaccines and therapeutics against various diseases. However, the overall accuracy and success rate need to be improved greatly to gain practical application significance, especially conformational epitope prediction. In this review, we examined the general features of antibody-antigen recognition, highlighting the conformation selection mechanism in flexible antibody-antigen binding. We recently highlighted the success and warning signs of antibody epitope predictions, including linear and conformation epitope predictions. While deep learning-based models gradually outperform traditional feature-based machine learning, sequence and structure features still provide insight into antibody-antigen recognition problems.
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Affiliation(s)
- Xincheng Zeng
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; (X.Z.); (C.S.)
| | - Ganggang Bai
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; (X.Z.); (C.S.)
| | - Chuance Sun
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; (X.Z.); (C.S.)
| | - Buyong Ma
- Engineering Research Center of Cell & Therapeutic Antibody (MOE), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; (X.Z.); (C.S.)
- Shanghai Digiwiser Biological, Inc., Shanghai 200131, China
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14
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A'la R, Wijaya AY, Susilowati H, Kuncorojakti S, Diyantoro, Rahmahani J, Rantam FA. Inactivated SARS-CoV-2 vaccine candidate immunization on non-human primate animal model: B-cell and T-cell responses immune evaluation. Heliyon 2023; 9:e18039. [PMID: 37519714 PMCID: PMC10372371 DOI: 10.1016/j.heliyon.2023.e18039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 06/21/2023] [Accepted: 07/05/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND SARS-CoV-2 vaccine was proven to be an effective and efficient measure for mitigating pandemic. COVID-19 infection and mortality subsided along with the increaseing COVID-19 vaccination coverage. Vaccine and health resource equity are predominant factors in COVID-19 pandemic management. Vaccine development for Indonesia, aims to ensure a sustainable pandemic control and steady national stability restoration. A decent vaccine must induce immunity against COVID-19 with minimum adverse reaction. Immunogenicity and ability to induce neutralizing antibody evaluation needs to be performed as part of the SARS-CoV-2 inactivated vaccine development from East Java, Indonesia isolate (Vaksin Merah Putih-INAVAC). OBJECTIVE This research demonstrated INAVAC performance in inducing the production neutralizing antibody along with its effects on CD4+ and CD8+ cells response in Macaca fascicularis (non-human primate). METHODS Two dosages of 3 μg and 5 μg were tested, compared to sham (NaCl 0.9%) in 10 Macaca fascicularis (2 injection intramuscular with 14 days interval). All animals were monitored daily for clinical signs. Nasopharyngeal samples were analyzed using qRT-PCR while the serum were tested using ELISA and neutralization assay, whereas PBMCs were flowcytrometrically analyzed to measure CD4+ and CD8+ population. RESULTS It is observed that both vaccine doses could stimulate relatively similar immune response and neutralizing antibody (end GMT post challenge = 905,1), whereas higher CD8+ cells response were reported in the 5 μg group after the 3rd day post-challenge. The dose of vaccine that produce adequate immune cell stimulation with neutralizing antibody induction can be adopted to clinical study, as favorable result of these parameters could predict minimum adverse reaction from inflammation response with balanced immune response. CONCLUSIONS Therefore, it is concluded that Vaksin Merah Putih-INAVAC with 3 μg dose showed a favorable potential to be developed and tested as human vaccine.
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Affiliation(s)
- Rofiqul A'la
- Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | - Helen Susilowati
- Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Suryo Kuncorojakti
- Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Diyantoro
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Indonesia
| | - Jola Rahmahani
- Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Fedik Abdul Rantam
- Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
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15
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Ning S, Chang HC, Fan KC, Hsiao PY, Feng C, Shoemaker D, Chen RT. A point-of-care biosensor for rapid detection and differentiation of COVID-19 virus (SARS-CoV-2) and influenza virus using subwavelength grating micro-ring resonator. APPLIED PHYSICS REVIEWS 2023; 10:021410. [PMID: 37265478 PMCID: PMC10228026 DOI: 10.1063/5.0146079] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 05/05/2023] [Indexed: 06/03/2023]
Abstract
In the context of continued spread of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 and the emergence of new variants, the demand for rapid, accurate, and frequent detection is increasing. Moreover, the new predominant strain, Omicron variant, manifests more similar clinical features to those of other common respiratory infections. The concurrent detection of multiple potential pathogens helps distinguish SARS-CoV-2 infection from other diseases with overlapping symptoms, which is significant for providing tailored treatment to patients and containing the outbreak. Here, we report a lab-on-a-chip biosensing platform for SARS-CoV-2 detection based on the subwavelength grating micro-ring resonator. The sensing surface is functionalized by specific antibody against SARS-CoV-2 spike protein, which could produce redshifts of resonant peaks by antigen-antibody combination, thus achieving quantitative detection. Additionally, the sensor chip is integrated with a microfluidic chip featuring an anti-backflow Y-shaped structure that enables the concurrent detection of two analytes. In this study, we realized the detection and differentiation of COVID-19 and influenza A H1N1. Experimental results indicate that the limit of detection of our device reaches 100 fg/ml (1.31 fM) within 15 min detecting time, and cross-reactivity tests manifest the specificity of the optical diagnostic assay. Furthermore, the integrated packaging and streamlined workflow facilitate its use for clinical applications. Thus, the biosensing platform presents a promising approach for attaining highly sensitive, selective, multiplexed, and quantitative point-of-care diagnosis and distinction between COVID-19 and influenza.
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Affiliation(s)
- Shupeng Ning
- Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, Texas 78758, USA
| | - Hao-Chen Chang
- Omega Optics, Inc., 8500 Shoal Creek Blvd., Austin, Texas 78757, USA
| | - Kang-Chieh Fan
- Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, Texas 78758, USA
| | - Po-Yu Hsiao
- Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, Texas 78758, USA
| | - Chenghao Feng
- Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, Texas 78758, USA
| | - Devan Shoemaker
- Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, Texas 78758, USA
| | - Ray T. Chen
- Author to whom correspondence should be addressed:
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16
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Taha BA, Al-Jubouri Q, Al Mashhadany Y, Hafiz Mokhtar MH, Bin Zan MSD, Bakar AAA, Arsad N. Density estimation of SARS-CoV2 spike proteins using super pixels segmentation technique. Appl Soft Comput 2023; 138:110210. [PMID: 36960080 PMCID: PMC10019041 DOI: 10.1016/j.asoc.2023.110210] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 04/14/2022] [Accepted: 03/07/2023] [Indexed: 03/18/2023]
Abstract
The worldwide outbreak of COVID-19 disease was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2). The existence of spike proteins, which allow these viruses to infect host cells, is one of the distinctive biological traits of various prior viruses. As a result, the process by which these viruses infect people is largely dependent on spike proteins. The density of SARS-CoV-2 spike proteins must be estimated to better understand and develop diagnostics and vaccines against the COVID-19 pandemic. CT scans and X-rays have three issues: frosted glass, consolidation, and strange roadway layouts. Each of these issues can be graded separately or together. Although CT scan is sensitive to COVID-19, it is not very specific. Therefore, patients who obtain these results should have more comprehensive clinical and laboratory tests to rule out other probable reasons. This work collected 586 SARS-CoV 2 transmission electron microscopy (TEM) images from open source for density estimation of virus spike proteins through a segmentation approach based on the superpixel technique. As a result, the spike density means of SARS-CoV2 and SARS-CoV were 21,97 nm and 22,45 nm, respectively. Furthermore, in the future, we aim to include this model in an intelligent system to enhance the accuracy of viral detection and classification. Moreover, we can remotely connect hospitals and public sites to conduct environmental hazard assessments and data collection.
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Affiliation(s)
- Bakr Ahmed Taha
- UKM-Department of Electrical, Electronic and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Malaysia
| | - Qussay Al-Jubouri
- Department of Communication Engineering, University of Technology, Baghdad, Iraq
| | - Yousif Al Mashhadany
- Department of Electrical Engineering, College of Engineering, University of Anbar, Anbar, 00964, Iraq
| | - Mohd Hadri Hafiz Mokhtar
- UKM-Department of Electrical, Electronic and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Malaysia
| | - Mohd Saiful Dzulkefly Bin Zan
- UKM-Department of Electrical, Electronic and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Malaysia
| | - Ahmad Ashrif A Bakar
- UKM-Department of Electrical, Electronic and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Malaysia
| | - Norhana Arsad
- UKM-Department of Electrical, Electronic and Systems Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Malaysia
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17
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Abebe EC, Dejenie TA. Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications. Front Immunol 2023; 14:1055457. [PMID: 36742320 PMCID: PMC9892939 DOI: 10.3389/fimmu.2023.1055457] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 01/03/2023] [Indexed: 01/20/2023] Open
Abstract
Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.
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Affiliation(s)
- Endeshaw Chekol Abebe
- Department of Medical Biochemistry, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Tadesse Asmamaw Dejenie
- Department of Medical Biochemistry, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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18
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Salma N, Hossain MM, Yasmin S, Alam MK, Rimon AR, Faruque J, Ali M. Factors influencing plasma donation behavior of COVID-19 recovered patients in Bangladesh: A pilot study. Health Sci Rep 2023; 6:e974. [PMID: 36479388 PMCID: PMC9718945 DOI: 10.1002/hsr2.974] [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: 05/10/2022] [Revised: 10/20/2022] [Accepted: 11/20/2022] [Indexed: 09/10/2024] Open
Abstract
Background and Aim The COVID-19 pandemic has plagued our lives for more than 2 years, and the preference for convalescent plasma (CP) as a life-saving treatment since CP has proven as a potential therapeutic option for acute COVID-19 patients who were suffering from severe disease. It is important to identify which factors are associated with plasma donation. Therefore, this study aimed to assess the associated factors for CP donation to COVID-19 patients. Methods A cross-sectional study was conducted online from December 21, 2021 to February 15, 2022 to identify different socio-demographic factors and knowledge related to CP donation. People who recovered from the COVID-19 infections and those who are willing to participate were included in the study. A total of 60 participants were included in the study. The data were analyzed using descriptive statistics, correlation matrix, and factor analysis. Results The analysis results confirm that 41.67% (n = 25) of the participants aged 26-30 years; among the recovered patients, only about 23% (n = 14) of the participants donated plasma. Though 97% (n = 58) of the participants agreed to donate plasma when it will be needed, however, when someone asked to donate plasma then 76.67% (n = 46) of the patients declined it. Findings depict that gender had a weak positive relationship with ever decline in plasma donation at 5% level of significance and the age of the participants inversely related to plasma donation. Conclusion Almost all the recovered participants were willing to donate plasma, however, due to a lack of knowledge and misconception, relatively few people actually did. This study reemphasizes the importance of health education to overcome the misconception about plasma donation, which is crucial for the treatment of COVID-19 infection.
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Affiliation(s)
- Nahid Salma
- Department of StatisticsJahangirnagar UniversitySavarDhakaBangladesh
| | | | - Sabina Yasmin
- Department of StatisticsJahangirnagar UniversitySavarDhakaBangladesh
| | | | | | - Jobaer Faruque
- Department of StatisticsJahangirnagar UniversitySavarDhakaBangladesh
| | - Mohammad Ali
- Directorate General of Health ServicesMohakhaliDhakaBangladesh
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19
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Chen H, Zhang L, Zhang W, Dai Z, Chen T, Wei Y, Chen M. Clinical characteristics and remission of nine cases with coronavirus disease 2019 infection in Zunyi, Southwest of China: A retrospective study. Medicine (Baltimore) 2022; 101:e31494. [PMID: 36595797 PMCID: PMC9794302 DOI: 10.1097/md.0000000000031494] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) has become a rock-ribbed public pandemic and caused substantial health concerns worldwide. In addition to therapeutic strategies, the epidemiologic features and clinical characteristics of patients responded to COVID-19 infection are of equal importance. The study aims to systematically evaluate the clinical presentations and remission of cases with COVID-19 infection in Zunyi, Southwest of China, and to determine the similarities and variations for further clinical classification and comprehensive treatment. Herein, we conducted a retrospective study upon 9 patients in Zunyi, southwest of China, including 1 mild (LPA), 5 severe (SPA) and 3 critical (CPA) types of COVID-19 infection. In details, the demographic data, historical epidemiology, previous medical history, clinical symptoms and complications, laboratory examination, chest imaging, treatment and outcomes of the patients were throughout explored. The non-normal distribution of the data was conducted by utilizing the SPSS software, and significant statistical differences were identified when P < .05. By retrospective analysis of the 9 cases, we found there were multifaceted similarities and differences among them in clinical representation. The patients collectively showed negative for nucleic acid test (NAT) and favorable prognosis after receiving comprehensive therapy such as hormonotherapy, hemopruification, and antiviral administration as well as respiratory support. On the basis of the information, we systematically dissected the clinical features and outcomes of the enrolled patients with COVID-19 and the accompanied multiple syndromes, which would serve as new references for clinical classification and comprehensive treatment. Analysis of clinical characteristics and therapeutic effect of 9 cases of novel coronavirus pneumonia (COVID-19), ChiCTR2000031930. Registered April 15, 2020 (retrospective registration).
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Affiliation(s)
- Hongjun Chen
- Department of Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Cerebrovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Leisheng Zhang
- Stem Cell Bank of Guizhou Province, Guizhou Health-Biotech Biotechnology Co., Ltd., Guiyang, China
- Jiangxi Research Center of Stem Cell Engineering, Jiangxi Health-Biotech Stem Cell Technology Co., Ltd., Shangrao, China
- Shandong Provincial Key Laboratory of Translational Medicine for Rheumatic and Immune Diseases, Qianfoshan Hospital & The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
| | - Wei Zhang
- Department of Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Cerebrovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Zhihua Dai
- Stem Cell Bank of Guizhou Province, Guizhou Health-Biotech Biotechnology Co., Ltd., Guiyang, China
| | - Tao Chen
- Department of Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Cerebrovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yiyong Wei
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Miao Chen
- Department of Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- * Correspondence: Miao Chen, Department of Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China (e-mail: )
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20
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Lim HT, Kok BH, Lim CP, Abdul Majeed AB, Leow CY, Leow CH. Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses. BIOMEDICAL ENGINEERING ADVANCES 2022; 4:100054. [PMID: 36158162 PMCID: PMC9482557 DOI: 10.1016/j.bea.2022.100054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 09/06/2022] [Accepted: 09/16/2022] [Indexed: 11/28/2022] Open
Abstract
With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.
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Key Words
-
γ
, Gamma
-
δ
, Delta
- ACE2, Angiotensin-converting enzyme 2
- ADCC, Antibody-dependent cell-mediated cytotoxicity
- ADCP, Antibody-dependent cellular phagocytosis
- ADE, Antibody-dependent enhancement
- Alb, Albumin
- Bat-SL-CoV, Bat SARS-like coronavirus
- Broad neutralization
- CDC, Complement-dependent cytotoxicity
- CDR, Complementarity-determining region
- CH, Constant domain of antibody heavy chain
- CHO, Chinese hamster ovary
- CL, Constant domain of antibody light chain
- CNAR, Constant domain of immunoglobulin new antigen receptor
- COVID-19
- COVID-19, Coronavirus disease 2019
- Cryo-EM, Cryogenic electron microscopy
- Cu, Copper
- DNA, Deoxyribonucleic acid
- DPP4, Dipeptidyl peptidase 4
- E, Envelope
- EC50, Half-maximal effective concentration
- FDA, The United States Food and Drug Administration
- Fab, Antigen-binding fragment
- Fc, Crystallisable fragment
- FcR, Crystallisable fragment receptor
- Fig., Figure
- HCoV, Human coronavirus
- HIV, Human immunodeficiency virus
- HR, Heptad repeat
- HRP, Horseradish peroxidase
- HV, Hypervariable region
- IC50, Half-maximal inhibitory concentration
- Ig, Immunoglobulin
- IgNAR, Immunoglobulin new antigen receptor
- KD, Equilibrium dissociation constant
- L, Litre
- LRT, Lower respiratory tract
- M, Membrane
- MERS, Middle East respiratory syndrome
- MERS-CoV, Middle East respiratory syndrome coronavirus
- N, Nucleocapsid
- ND50, 50% neutralizing dose
- NTD, N-terminal domain
- Nb, Nanobody
- PCR, Polymerase chain reaction
- PEG, Polyethylene glycol
- RBD, Receptor-binding domain
- RBM, Receptor-binding motif
- RNA, Ribonucleic acid
- S, Spike
- SARS, Severe acute respiratory syndrome
- SARS-CoV, Severe acute respiratory syndrome coronavirus
- SARS-CoV-2 mutation
- SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2
- SPAAC, Strain-promoted azide-alkyne cycloaddition
- Single-domain antibody
- Spike protein
- TMPRSS2, Transmembrane serine protease 2
- Therapeutic
- URT, Upper respiratory tract
- VH, Variable domain of antibody heavy chain
- VHH, Variable domain of camelid heavy-chain only antibody
- VL, Variable domain of antibody light chain
- VNAR, Variable domain of immunoglobulin new antigen receptor
- WHO, World Health Organization
- cDNA, Complementary deoxyribonucleic acid
- dpi, Days' post infection
- g, Gram
- kDa, Kilodalton
- koff, Dissociation rate constant
- mAb, Monoclonal antibody
- mRNA, Messenger ribonucleic acid
- nM, Nanomolar
- pM, Picomolar
- scFv, Single-chain variable fragment
- sdAb, Single-domain antibody
- ß, Beta
- α, Alpha
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Affiliation(s)
- H T Lim
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia
| | - B H Kok
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia
| | - C P Lim
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia
| | - A B Abdul Majeed
- Faculty of Pharmacy, Universiti Teknologi MARA, Kampus Puncak Alam, Bandar Puncak Alam, Selangor 42300, Malaysia
| | - C Y Leow
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia
| | - C H Leow
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia
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21
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Targeted therapy in Coronavirus disease 2019 (COVID-19): Implication from cell and gene therapy to immunotherapy and vaccine. Int Immunopharmacol 2022; 111:109161. [PMID: 35998506 PMCID: PMC9385778 DOI: 10.1016/j.intimp.2022.109161] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/27/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19.
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22
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Wang S, Wu D, Xiong H, Wang J, Tang Z, Chen Z, Wang Y, Zhang Y, Ying D, Lin X, Liu C, Guo S, Tian W, Lin Y, Zhang X, Yuan Q, Yu H, Zhang T, Zheng Z, Xia N. Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines. Front Immunol 2022; 13:952650. [PMID: 36203593 PMCID: PMC9530325 DOI: 10.3389/fimmu.2022.952650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 09/05/2022] [Indexed: 11/13/2022] Open
Abstract
Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.
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Affiliation(s)
- Siling Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Dinghui Wu
- Department of Pulmonary Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Hualong Xiong
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Juan Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Zimin Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Zihao Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Yizhen Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Yali Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Dong Ying
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Xue Lin
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Chang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Shaoqi Guo
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Weikun Tian
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Yajie Lin
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Xiaoping Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Quan Yuan
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Hai Yu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
| | - Tianying Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- *Correspondence: Tianying Zhang, ; Zizheng Zheng, ; Ningshao Xia,
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- *Correspondence: Tianying Zhang, ; Zizheng Zheng, ; Ningshao Xia,
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China
- *Correspondence: Tianying Zhang, ; Zizheng Zheng, ; Ningshao Xia,
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23
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Quantitation and Identification of Therapeutic Anti-CD22 Monoclonal Antibodies in a Cell-Based ELISA Method. Antibodies (Basel) 2022; 11:antib11030053. [PMID: 35997347 PMCID: PMC9396980 DOI: 10.3390/antib11030053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/04/2022] [Accepted: 08/12/2022] [Indexed: 11/20/2022] Open
Abstract
Since they lack native soluble membrane antigens, the analysis and selection of antigen-specific antibodies are commonly performed on whole live cells. Here, we have developed a simple and convenient enzyme-linked immunosorbent assay (ELISA) based on cell membrane antigens. Soluble cell membrane proteins isolated from Raji cells were immobilized on the polystyrene microplate, which permitted the assessment of a therapeutic anti-CD22 monoclonal antibody. The experiments showed less variability in the intra-assay. Compared to the living cell ELISAs, the advantage of the assay is avoiding cell losses and high variation of optical density (OD) readings. We provide a quantitative and reproducible ELISA that can be potentially applied to the development of specific antibodies against cell surface antigens.
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24
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Jowkar G, Pečerska J, Maiolo M, Gil M, Anisimova M. ARPIP: Ancestral sequence Reconstruction with insertions and deletions under the Poisson Indel Process. Syst Biol 2022:6648472. [PMID: 35866991 DOI: 10.1093/sysbio/syac050] [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: 11/04/2021] [Accepted: 07/06/2022] [Indexed: 11/12/2022] Open
Abstract
Modern phylogenetic methods allow inference of ancestral molecular sequences given an alignment and phylogeny relating present day sequences. This provides insight into the evolutionary history of molecules, helping to understand gene function and to study biological processes such as adaptation and convergent evolution across a variety of applications. Here we propose a dynamic programming algorithm for fast joint likelihood-based reconstruction of ancestral sequences under the Poisson Indel Process (PIP). Unlike previous approaches, our method, named ARPIP, enables the reconstruction with insertions and deletions based on an explicit indel model. Consequently, inferred indel events have an explicit biological interpretation. Likelihood computation is achieved in linear time with respect to the number of sequences. Our method consists of two steps, namely finding the most probable indel points and reconstructing ancestral sequences. First, we find the most likely indel points and prune the phylogeny to reflect the insertion and deletion events per site. Second, we infer the ancestral states on the pruned subtree in a manner similar to FastML. We applied ARPIP on simulated datasets and on real data from the Betacoronavirus genus. ARPIP reconstructs both the indel events and substitutions with a high degree of accuracy. Our method fares well when compared to established state-of-the-art methods such as FastML and PAML. Moreover, the method can be extended to explore both optimal and suboptimal reconstructions, include rate heterogeneity through time and more. We believe it will expand the range of novel applications of ancestral sequence reconstruction.
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Affiliation(s)
- Gholamhossein Jowkar
- Zurich University of Applied Sciences, School of Life Sciences and Facility Management, CH-8820, Wädenswil, Switzerland.,Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.,University of Neuchâtel, Institute of biology, CH-2000 Neuchâtel, Switzerland
| | - Jūlija Pečerska
- Zurich University of Applied Sciences, School of Life Sciences and Facility Management, CH-8820, Wädenswil, Switzerland.,Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
| | - Massimo Maiolo
- Zurich University of Applied Sciences, School of Life Sciences and Facility Management, CH-8820, Wädenswil, Switzerland.,Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.,University of Bern, Institute of Pathology, CH-3008 Bern, Switzerland
| | - Manuel Gil
- Zurich University of Applied Sciences, School of Life Sciences and Facility Management, CH-8820, Wädenswil, Switzerland.,Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
| | - Maria Anisimova
- Zurich University of Applied Sciences, School of Life Sciences and Facility Management, CH-8820, Wädenswil, Switzerland.,Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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25
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Ssenyange G, Kerfoot M, Zhao M, Farhadian S, Chen S, Peng L, Ren P, Dela Cruz CS, Gupta S, Sutton RE. Development of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 spike interaction with hACE2. CELL REPORTS METHODS 2022; 2:100252. [PMID: 35757815 PMCID: PMC9213030 DOI: 10.1016/j.crmeth.2022.100252] [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] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 04/28/2022] [Accepted: 06/14/2022] [Indexed: 06/15/2023]
Abstract
Efficient quantitative assays for measurement of viral replication and infectivity are indispensable for future endeavors to develop prophylactic or therapeutic antiviral drugs or vaccines against SARS-CoV-2. We developed a SARS-CoV-2 cell-cell transmission assay that provides a rapid and quantitative readout to assess SARS-CoV-2 spike hACE2 interaction in the absence of pseudotyped particles or live virus. We established two well-behaved stable cell lines, which demonstrated a remarkable correlation with standard cell-free viral pseudotyping for inhibition by convalescent sera, small-molecule drugs, and murine anti-spike monoclonal antibodies. The assay is rapid, reliable, and highly reproducible, without a requirement for any specialized research reagents or laboratory equipment and should be easy to adapt for use in most investigative and clinical settings. It can be effectively used or modified for high-throughput screening for compounds and biologics that interfere with virus-cell binding and entry to complement other neutralization assays currently in use.
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Affiliation(s)
- George Ssenyange
- Department of Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06510, USA
| | - Maya Kerfoot
- Department of Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06510, USA
| | - Min Zhao
- Department of Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06510, USA
| | - Shelli Farhadian
- Department of Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06510, USA
| | - Sidi Chen
- Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA
| | - Lei Peng
- Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA
| | - Ping Ren
- Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA
| | - Charles S. Dela Cruz
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, Yale School of Medicine, New Haven, CT 06510, USA
| | - Shaili Gupta
- Department of Medicine, Section of General Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA
- Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, CT 06516, USA
| | - Richard E. Sutton
- Department of Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06510, USA
- Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, CT 06516, USA
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26
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Hajikarimlou M, Hooshyar M, Moutaoufik M, Aly K, Azad T, Takallou S, Jagadeesan S, Phanse S, Said K, Samanfar B, Bell J, Dehne F, Babu M, Golshani A. A computational approach to rapidly design peptides that detect SARS-CoV-2 surface protein S. NAR Genom Bioinform 2022; 4:lqac058. [PMID: 36004308 PMCID: PMC9394169 DOI: 10.1093/nargab/lqac058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 06/10/2022] [Accepted: 08/01/2022] [Indexed: 11/12/2022] Open
Abstract
Abstract
The coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted the development of diagnostic and therapeutic frameworks for timely containment of this pandemic. Here, we utilized our non-conventional computational algorithm, InSiPS, to rapidly design and experimentally validate peptides that bind to SARS-CoV-2 spike (S) surface protein. We previously showed that this method can be used to develop peptides against yeast proteins, however, the applicability of this method to design peptides against other proteins has not been investigated. In the current study, we demonstrate that two sets of peptides developed using InSiPS method can detect purified SARS-CoV-2 S protein via ELISA and Surface Plasmon Resonance (SPR) approaches, suggesting the utility of our strategy in real time COVID-19 diagnostics. Mass spectrometry-based salivary peptidomics shortlist top SARS-CoV-2 peptides detected in COVID-19 patients’ saliva, rendering them attractive SARS-CoV-2 diagnostic targets that, when subjected to our computational platform, can streamline the development of potent peptide diagnostics of SARS-CoV-2 variants of concern. Our approach can be rapidly implicated in diagnosing other communicable diseases of immediate threat.
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Affiliation(s)
- Maryam Hajikarimlou
- Ottawa Institute of Systems Biology, University of Ottawa , Health Science Campus, Ottawa , Ontario , Canada
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
| | - Mohsen Hooshyar
- Ottawa Institute of Systems Biology, University of Ottawa , Health Science Campus, Ottawa , Ontario , Canada
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
| | - Mohamed Taha Moutaoufik
- Department of Biochemistry, Research and Innovation Centre, University of Regina , Regina , Canada
| | - Khaled A Aly
- Department of Biochemistry, Research and Innovation Centre, University of Regina , Regina , Canada
| | - Taha Azad
- The Ottawa Hospital Research Institute 501 Smyth Road , Ottawa , Ontario , Canada
| | - Sarah Takallou
- Ottawa Institute of Systems Biology, University of Ottawa , Health Science Campus, Ottawa , Ontario , Canada
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
| | - Sasi Jagadeesan
- Ottawa Institute of Systems Biology, University of Ottawa , Health Science Campus, Ottawa , Ontario , Canada
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
| | - Sadhna Phanse
- Department of Biochemistry, Research and Innovation Centre, University of Regina , Regina , Canada
| | - Kamaledin B Said
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
- Department of Pathology and Microbiology, College of Medicine, University of Hail , Saudi Arabia
| | - Bahram Samanfar
- Ottawa Institute of Systems Biology, University of Ottawa , Health Science Campus, Ottawa , Ontario , Canada
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
- Agriculture and Agri-Food Canada, Ottawa Research and Development Centre (ORDC) , Ottawa , Ontario , Canada
| | - John C Bell
- The Ottawa Hospital Research Institute 501 Smyth Road , Ottawa , Ontario , Canada
| | - Frank Dehne
- School of Computer Science, Carleton University , Ottawa , Ontario , Canada
| | - Mohan Babu
- Department of Biochemistry, Research and Innovation Centre, University of Regina , Regina , Canada
| | - Ashkan Golshani
- Ottawa Institute of Systems Biology, University of Ottawa , Health Science Campus, Ottawa , Ontario , Canada
- Department of Biology, Carleton University , Ottawa , Ontario , Canada
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27
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Emergence of SARS-CoV-2 New Variants and Their Clinical Significance. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2022; 2022:7336309. [PMID: 35669528 PMCID: PMC9167142 DOI: 10.1155/2022/7336309] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/17/2022] [Accepted: 04/28/2022] [Indexed: 12/23/2022]
Abstract
COVID-19 is a respiration-related disease caused by SARS-CoV-2 and was identified in China's Wuhan city. More than 223 countries are affected by the disease worldwide. The new variants of the COVID-19 virus are causing problems, from average to life-threatening pneumonia and acute respiratory distress syndrome (ARDS). Presently, there are 170 vaccine candidates, out of which 10 have been approved by the WHO for vaccination, such as Ad26.COV2.S, Pfizer/BioNTech, COVISHIELD, Covovax, Moderna, KoviVac, and some other vaccines to combat the deadly SARS-CoV-2 infection. From all these vaccines, Pfizer/BioNTech and Moderna are showing the highest efficacy against COVID-19. These vaccines are highly efficient against COVID-19 disease, but their potentiality against new variants remains a question. COVID-19 vaccines are highly effective at preventing severe illnesses, hospitalizations, and death. The antibodies elicited by earlier infection or vaccination are the key for possible protection against SARS-CoV-2. The problem has been exacerbated by new information from Africa on the origins of the novel contagious SARS-CoV-2 strain. These new strains occur due to unique mutations in the spike protein, which modify SARS-CoV-2 transmission and infection capabilities, limiting the efficacy of the COVID-19 vaccination. Hence, there is a need to find a potential vaccine against it.
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28
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Hassan J, Haigh C, Ahmed T, Uddin MJ, Das DB. Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges. Pharmaceutics 2022; 14:1066. [PMID: 35631652 PMCID: PMC9144974 DOI: 10.3390/pharmaceutics14051066] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/27/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022] Open
Abstract
To prevent the coronavirus disease 2019 (COVID-19) pandemic and aid restoration to prepandemic normality, global mass vaccination is urgently needed. Inducing herd immunity through mass vaccination has proven to be a highly effective strategy for preventing the spread of many infectious diseases, which protects the most vulnerable population groups that are unable to develop immunity, such as people with immunodeficiencies or weakened immune systems due to underlying medical or debilitating conditions. In achieving global outreach, the maintenance of the vaccine potency, transportation, and needle waste generation become major issues. Moreover, needle phobia and vaccine hesitancy act as hurdles to successful mass vaccination. The use of dissolvable microneedles for COVID-19 vaccination could act as a major paradigm shift in attaining the desired goal to vaccinate billions in the shortest time possible. In addressing these points, we discuss the potential of the use of dissolvable microneedles for COVID-19 vaccination based on the current literature.
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Affiliation(s)
- Jasmin Hassan
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (J.H.); (T.A.)
| | - Charlotte Haigh
- Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK;
| | - Tanvir Ahmed
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (J.H.); (T.A.)
| | - Md Jasim Uddin
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (J.H.); (T.A.)
- Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Kent ME4 4TB, UK
- Department of Pharmacy, Brac University, 66 Mohakhali, Dhaka 1212, Bangladesh
| | - Diganta B. Das
- Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK;
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Zhang Z, Jiang S, Wang X, Dong T, Wang Y, Li D, Gao X, Qu Z, Li Y. A novel enhanced substrate for label-free detection of SARS-CoV-2 based on surface-enhanced Raman scattering. SENSORS AND ACTUATORS. B, CHEMICAL 2022; 359:131568. [PMID: 35185297 PMCID: PMC8839800 DOI: 10.1016/j.snb.2022.131568] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 01/20/2022] [Accepted: 02/10/2022] [Indexed: 05/08/2023]
Abstract
Accurate and sensitive detection of SARS-CoV-2 is an effective strategy for preventing the COVID-19 pandemic in the current absence of specific drug therapy. This study presents a novel enhanced substrate for label-free detection of respiratory viruses using surface-enhanced Raman Scattering. Sodium borohydride reduces silver ions to clustered silver nanoparticles to eliminate the disorganized peak signal of the traditional citrate reducing agent. Meanwhile, the study obtained the fingerprints and concentration-dependent curves of many respiratory viruses, including SARS-CoV-2, human adenovirus type 7, and H1N1 virus, with good linear relationships. The three viruses were also identified in serum and saliva within two minutes, combined with linear discriminant diagnostic analysis. Therefore, establishing this enhanced substrate is greatly valuable for the global response to the COVID-19 pandemic.
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Affiliation(s)
- Zhe Zhang
- College of Pharmacy, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
- College of Public Health, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
- Research Center for Innovative Technology of Pharmaceutical Analysis, Baojian Road No. 157, Harbin, Heilongjiang Province, 150081, China
| | - Shen Jiang
- College of Pharmacy, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
- Research Center for Innovative Technology of Pharmaceutical Analysis, Baojian Road No. 157, Harbin, Heilongjiang Province, 150081, China
| | - Xiaotong Wang
- College of Pharmacy, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
- Research Center for Innovative Technology of Pharmaceutical Analysis, Baojian Road No. 157, Harbin, Heilongjiang Province, 150081, China
| | - Tuo Dong
- College of Public Health, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
| | - Yunpeng Wang
- College of Pharmacy, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
- Research Center for Innovative Technology of Pharmaceutical Analysis, Baojian Road No. 157, Harbin, Heilongjiang Province, 150081, China
| | - Dan Li
- Institute of Physics, Guizhou University, South Section of Huaxi Avenue No. 2708, Guiyang, Guizhou Province, 550025, China
| | - Xin Gao
- Institute of Physics, Guizhou University, South Section of Huaxi Avenue No. 2708, Guiyang, Guizhou Province, 550025, China
| | - Zhangyi Qu
- College of Public Health, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
| | - Yang Li
- College of Pharmacy, Harbin Medical University, Baojian Road No. 157, Harbin, Heilongjiang Province 150081, China
- Research Center for Innovative Technology of Pharmaceutical Analysis, Baojian Road No. 157, Harbin, Heilongjiang Province, 150081, China
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30
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Kim JK, Ryu SW, Kim JS, Jung BK. Performance evaluation of four rapid antibody tests for the detection of severe acute respiratory syndrome coronavirus 2. J Clin Lab Anal 2022; 36:e24374. [PMID: 35446996 PMCID: PMC9110950 DOI: 10.1002/jcla.24374] [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: 02/08/2022] [Revised: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 11/18/2022] Open
Abstract
Background The prompt detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is important in the therapeutic management of infected patients. Rapid diagnostic tests are widely used for this purpose. This study aimed to evaluate the clinical performance of four SARS‐CoV‐2 immunoglobulin IgG/IgM rapid diagnostic tests in the detection of SARS‐CoV‐2. Methods Nasopharyngeal and oropharyngeal swabs and/or sputum were collected from 30 patients infected with SARS‐CoV‐2 and 30 healthy volunteers. All specimens were tested using four SARS‐CoV‐2 IgG/IgM rapid diagnostic tests and real‐time polymerase chain reaction. We assessed the clinical sensitivity and specificity of the tests. Results The clinical sensitivity of FREND™, SsmarTest™, BIOCREDIT™, and IVDLAB™ was 96.67%, 100.00%, 100.00%, and 96.67%, respectively, compared to real‐time polymerase chain reaction. The clinical specificity was 96.67%, 100.00%, 86.67%, and 96.67%, respectively. Conclusion These findings could expedite the detection of SARS‐CoV‐2 and thus reduce the risk of further transmission of the virus.
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Affiliation(s)
- Jae Kyung Kim
- Department of Biomedical Laboratory Science, Dankook University College of Health Sciences, Cheonan, Korea
| | - Sook Won Ryu
- Department of Laboratory Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea
| | - Jae Soo Kim
- Department of Laboratory Medicine, Dankook University Hospital, Cheonan, Korea
| | - Bo Kyeung Jung
- Department of Laboratory Medicine, Dankook University College of Medicine, Cheonan, Korea
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31
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Mir I, Aamir S, Shah SRH, Shahid M, Amin I, Afzal S, Nawaz A, Khan MU, Idrees M. Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic. Osong Public Health Res Perspect 2022; 13:84-100. [PMID: 35538681 PMCID: PMC9091641 DOI: 10.24171/j.phrp.2022.0024] [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: 01/17/2022] [Revised: 03/15/2022] [Accepted: 04/10/2022] [Indexed: 12/15/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNAbased vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.
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Affiliation(s)
- Iqra Mir
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Sania Aamir
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Syed Rizwan Hussain Shah
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Muhammad Shahid
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Iram Amin
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Samia Afzal
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Amjad Nawaz
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Muhammad Umer Khan
- University Institute of Medical lab Technology, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Muhammad Idrees
- Division of Molecular Virology and Infectious Diseases, National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
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32
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Wu W, Tan X, Zupancic J, Schardt JS, Desai AA, Smith MD, Zhang J, Xie L, Oo MK, Tessier PM, Fan X. Rapid and Quantitative In Vitro Evaluation of SARS-CoV-2 Neutralizing Antibodies and Nanobodies. Anal Chem 2022; 94:4504-4512. [PMID: 35238533 PMCID: PMC9356539 DOI: 10.1021/acs.analchem.2c00062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Neutralizing monoclonal antibodies and nanobodies have shown promising results as potential therapeutic agents for COVID-19. Identifying such antibodies and nanobodies requires evaluating the neutralization activity of a large number of lead molecules via biological assays, such as the virus neutralization test (VNT). These assays are typically time-consuming and demanding on-lab facilities. Here, we present a rapid and quantitative assay that evaluates the neutralizing efficacy of an antibody or nanobody within 1.5 h, does not require BSL-2 facilities, and consumes only 8 μL of a low concentration (ng/mL) sample for each assay run. We tested the human angiotensin-converting enzyme 2 (ACE2) binding inhibition efficacy of seven antibodies and eight nanobodies and verified that the IC50 values of our assay are comparable with those from SARS-CoV-2 pseudovirus neutralization tests. We also found that our assay could evaluate the neutralizing efficacy against three widespread SARS-CoV-2 variants. We observed increased affinity of these variants for ACE2, including the β and γ variants. Finally, we demonstrated that our assay enables the rapid identification of an immune-evasive mutation of the SARS-CoV-2 spike protein, utilizing a set of nanobodies with known binding epitopes.
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Affiliation(s)
- Weishu Wu
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - Xiaotian Tan
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - Jennifer Zupancic
- Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.,Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - John S Schardt
- Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.,Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.,Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - Alec A Desai
- Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.,Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - Matthew D Smith
- Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.,Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - Jie Zhang
- Beijing Key Laboratory of Monoclonal Antibody Research and Development, Sino Biological Inc., Beijing 100176, China
| | - Liangzhi Xie
- Beijing Key Laboratory of Monoclonal Antibody Research and Development, Sino Biological Inc., Beijing 100176, China.,Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China
| | - Maung Khaing Oo
- Optofluidic Bioassay, LLC, Ann Arbor, Michigan 48103, United States
| | - Peter M Tessier
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.,Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.,Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.,Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States
| | - Xudong Fan
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States
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33
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Ma Z, Zhu M, Zhang S, Qian K, Wang C, Fu W, Lei C, Hu S. Therapeutic antibodies under development for SARS-CoV-2. VIEW 2022; 3:20200178. [PMID: 34766160 PMCID: PMC8441747 DOI: 10.1002/viw.20200178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 03/11/2021] [Accepted: 06/01/2021] [Indexed: 01/08/2023] Open
Abstract
The world is experiencing one of the most difficult moments in history with COVID-19, which has rapidly developed into a worldwide pandemic with a significant health and economic burden. Efforts to fight the virus, including prevention and treatment, have never stopped. However, no specific drugs or treatments have yet been found. Antibody drugs have never been absent in epidemics such as SARS, MERS, HIV, Ebola, and so on in the past two decades. At present, while research on the SARS-CoV-2 vaccine is in full swing, antibody drugs are also receiving widespread attention. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Here, we summarize the therapeutic antibodies against SARS-CoV-2, as well as the research using ACE2 recombinant protein or ACE2-Ig fusion protein.
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Affiliation(s)
- Zetong Ma
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
| | - MengMei Zhu
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
- Team SMMU‐China of the International Genetically Engineered Machine (iGEM) competitionDepartment of BiophysicsSecond Military Medical UniversityShanghaiChina
| | - Shuyi Zhang
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
| | - Kewen Qian
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
- Team SMMU‐China of the International Genetically Engineered Machine (iGEM) competitionDepartment of BiophysicsSecond Military Medical UniversityShanghaiChina
| | - Chuqi Wang
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
- Team SMMU‐China of the International Genetically Engineered Machine (iGEM) competitionDepartment of BiophysicsSecond Military Medical UniversityShanghaiChina
| | - Wenyan Fu
- Department of Assisted ReproductionShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Changhai Lei
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
| | - Shi Hu
- Department of BiophysicsCollege of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
- Team SMMU‐China of the International Genetically Engineered Machine (iGEM) competitionDepartment of BiophysicsSecond Military Medical UniversityShanghaiChina
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34
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Esharkawy ER, Almalki F, Hadda TB. In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa. Bioorg Chem 2022; 120:105587. [PMID: 35026560 PMCID: PMC8719923 DOI: 10.1016/j.bioorg.2021.105587] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 12/19/2021] [Accepted: 12/26/2021] [Indexed: 12/12/2022]
Abstract
Inflammation, oxidation, and compromised immunity all increase the dangers of COVID-19, whereas many pharmaceutical protocols may lead to increased immunity such as ingesting from sources containing vitamin E and zinc. A global search for natural remedies to fight COVID-19 has emerged, to assist in the treatment of this infamous coronavirus. Nigella satvia is a world-renowned plant, an esteemed herbal remedy, which can be used as a liquid medicine to increase immunity while decreasing the dangers of acute respiratory distress syndrome. Thymoqinone (TQ), dithymoqinone (DTQ) and thymohydroquinone (THQ), are major compounds of the essential oil contained in N.sativa. A current study aims to discover the antiviral activity of two compounds, Thymohydroquinone and Dithymoquinone, which are synthesized through simple chemical procedures, deriving from thymoquinone, which happens to be a major compound of Nigella sativa. A half-maximal cytotoxic concentration, "CC50", was calculated by MTT assay for each individual drug, The sample showed anti-SARS-CoV-2 activity at non-cytotoxic nanomolar concentrations in vitro with a low selectivity index (CC50/IC50 = 31.74/23.15 = 1.4), whereby Dimthymoquinone shows high cytotoxicity.
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Affiliation(s)
- Eman R Esharkawy
- Department of Chemistry, College of Science, Northern Border University, Arar, Saudi Arabia.
| | - Faisal Almalki
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Taibi Ben Hadda
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia; Laboratory of Applied Chemistry & Environment, Faculty of Sciences, Mohammed Premier University, MB 524, 60000 Oujda, Morocco
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35
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Cruz VB, Júnior LFFF, Kobal CR, da Silva NA. Does sensitization by SARS-CoV-2 immune complexes trigger DRESS syndrome? Braz J Infect Dis 2022; 26:102337. [PMID: 35276095 PMCID: PMC8882399 DOI: 10.1016/j.bjid.2022.102337] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 01/18/2022] [Accepted: 02/16/2022] [Indexed: 12/17/2022] Open
Abstract
The diagnosis of coronavirus disease (COVID-19) has been a great challenge since the infection affects not only the respiratory system, but also different organs, given the intense inflammatory and autoimmune reaction triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein we present a case of a 36-year-old male patient, with some comorbidities and previous use of carbamazepine, who developed a severe condition triggered by COVID-19, including extensive exfoliative erythroderma and severe impairment of liver function, which lasted approximately 80 days.
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Affiliation(s)
- Virgínia Barbeitos Cruz
- Health Sciences Program, School of Medicine, Universidade Federal de Goiás, Goiânia, GO, Brazil.
| | | | - Christiane Reis Kobal
- Department of Infectious Diseases, Hospital of Tropical Diseases of Goiás, Goiânia, GO, Brazil
| | - Nilzio Antonio da Silva
- Health Sciences Program, School of Medicine, Universidade Federal de Goiás, Goiânia, GO, Brazil
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36
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Benefits from Shortening Viral Shedding by Traditional Chinese Medicine Treatment for Moderate COVID-19: An Observational Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7179050. [PMID: 35154352 PMCID: PMC8825291 DOI: 10.1155/2022/7179050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 11/27/2021] [Indexed: 11/18/2022]
Abstract
Traditional Chinese medicine (TCM) treatment for the coronavirus disease 2019 (COVID-19) can improve clinical symptoms, but it is not clear whether it can shorten viral shedding. This is an observational study including 97 patients with COVID-19 who were consecutively admitted to the Jiangxia Fangcang hospital in Wuhan (Hubei, China) from January 15, 2020, to March 10, 2020. All patients were treated with TCM, and we assessed the patients daily and collected clinical information via a diary card. The primary endpoint was the time to achieve a negative result for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RT-PCR. The final analysis included 92 patients. The median time to negative oropharyngeal swab for all the participants was 22 days (IQR 15–30). The participants were divided into three groups according to time from symptom onset to start of TCM treatment: within 7 days group (early treatment group), 8–14 days group (middle treatment group), and over 14 days group (late treatment group). The median time to negative oropharyngeal swab for the early treatment group was 14 days (IQR 12–17) and for the middle and late treatment groups was statistically shorter than 20 days (IQR 18–22) and 30 days (IQR 25–34), respectively. In univariate Cox proportional hazards regression analysis, the incidence of negative oropharyngeal swab for the early and middle treatment groups was 7.674 times and 3.609 times statistically higher than the late treatment group, respectively; whereas in multivariate Cox proportional hazards regression analysis, the incidence for the early and middle treatment groups was 18.093 times and 5.804 times statistically higher than the late treatment group, respectively. In patients with moderate COVID-19, those who had no cough, no dyspnea, and those who received TCM treatment earlier could achieve nucleic acid negative sooner by shortening viral shedding.
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37
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Liang Z, Peng T, Jiao X, Zhao Y, Xie J, Jiang Y, Meng B, Fang X, Yu X, Dai X. Latex Microsphere-Based Bicolor Immunochromatography for Qualitative Detection of Neutralizing Antibody against SARS-CoV-2. BIOSENSORS 2022; 12:bios12020103. [PMID: 35200362 PMCID: PMC8869495 DOI: 10.3390/bios12020103] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/26/2022] [Accepted: 02/02/2022] [Indexed: 05/12/2023]
Abstract
Neutralizing antibody (NAb) is a family of antibodies with special functions, which afford a degree of protection against infection and/or reduce the risk of clinically severe infection. Receptor binding domain (RBD) in the spike protein of SARS-CoV-2, a portion of the S1 subunit, can stimulate the immune system to produce NAb after infection and vaccination. The detection of NAb against SARS-CoV-2 is a simple and direct approach for evaluating a vaccine's effectiveness. In this study, a direct, rapid, and point-of-care bicolor lateral flow immunoassay (LFIA) was developed for NAb against SARS-CoV-2 detection without sample pretreatment, and which was based on the principle of NAb-mediated blockage of the interaction between RBD and angiotensin-converting enzyme 2. In the bicolor LFIA, red and blue latex microspheres (LMs) were used to locate the test and control lines, leading to avoidance of erroneous interpretations of one-colored line results. Under the optimal conditions, NAb against SARS-CoV-2 detection carried out using the bicolor LFIA could be completed within 9 min, and the visible limit of detection was about 48 ng/mL. Thirteen serum samples were analyzed, and the results showed that the NAb levels in three positive serum samples were equal to, or higher than, 736 ng/mL. The LM-based bicolor LFIA allows one-step, rapid, convenient, inexpensive, and user-friendly determination of NAb against SARS-CoV-2 in serum.
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Affiliation(s)
- Zhanwei Liang
- College of Life Sciences, China Jiliang University, Hangzhou 310018, China; (Z.L.); (X.J.)
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Tao Peng
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Xueshima Jiao
- College of Life Sciences, China Jiliang University, Hangzhou 310018, China; (Z.L.); (X.J.)
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Yang Zhao
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Jie Xie
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - You Jiang
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Bo Meng
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Xiang Fang
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
| | - Xiaoping Yu
- College of Life Sciences, China Jiliang University, Hangzhou 310018, China; (Z.L.); (X.J.)
- Correspondence: (X.Y.); (X.D.); Tel./Fax: +86-010-645-24962 (X.D.)
| | - Xinhua Dai
- Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China; (T.P.); (Y.Z.); (J.X.); (Y.J.); (B.M.); (X.F.)
- Correspondence: (X.Y.); (X.D.); Tel./Fax: +86-010-645-24962 (X.D.)
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Bian S, Shang M, Sawan M. Rapid biosensing SARS-CoV-2 antibodies in vaccinated healthy donors. Biosens Bioelectron 2022; 204:114054. [PMID: 35151002 PMCID: PMC8810518 DOI: 10.1016/j.bios.2022.114054] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 11/23/2021] [Accepted: 01/27/2022] [Indexed: 01/06/2023]
Abstract
In this study, we report two fiber optic-biolayer interferometry (FO-BLI)-based biosensors for the rapid detection of SARS-CoV-2 neutralizing antibodies (NAbs) and binding antibodies (BAbs) in human serum. The use of signal enhancer 3,3′-diaminobenzidine enabled the detection of NAbs, anti-receptor binding domain (anti-RBD) BAbs, and anti-extracellular domain of spike protein (anti-S-ECD) BAbs up to as low as 10 ng/mL in both buffer and 100-fold diluted serum. NAbs and BAbs could be detected individually over 7.5 and 13 min, respectively, or simultaneously by prolonging the detection time of the former. The protocol for the detection of BAbs could be utilized for detection of the RBD-N501Y variant with equal sensitivity and speed. Results of the NAbs and the anti-RBD BAbs biosensors correlated well with those of the corresponding commercial assay kit. Clinical utility of the two FO-BLI biosensors were further validated using a small cohort of samples randomly taken from 16 enrolled healthy participants who received inactivated vaccines. Two potent serum antibodies were identified, which showed high neutralizing capacities toward RBD and pseudovirus. Overall, the rapid automated biosensors can be used for an individual sample measurement of NAbs and BAbs as well as for high-throughput analysis. The findings of this study would be useful in COVID-19 related studies in vaccine trials, research on dynamics of the immune response, and epidemiology studies.
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Affiliation(s)
- Sumin Bian
- CenBRAIN, School of Engineering, Westlake University, China
| | - Min Shang
- Dept. of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China
| | - Mohamad Sawan
- CenBRAIN, School of Engineering, Westlake University, China.
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Ahmad W, Shabbiri K. Two years of SARS-CoV-2 infection (2019-2021): structural biology, vaccination, and current global situation. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022; 34:5. [PMID: 35043040 PMCID: PMC8759062 DOI: 10.1186/s43162-021-00092-7] [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: 10/23/2021] [Accepted: 12/03/2021] [Indexed: 11/10/2022] Open
Abstract
The deadly SARS-CoV-2 virus has infected more than 259,502,031 confirmed cases with 5,183,003 deaths in 223 countries during the last 22 months (Dec 2019-Nov 2021), whereas approximately 7,702,859,718, vaccine doses have been administered (WHO: https://covid19.who.int/) as of the 24th of Nov 2021. Recent announcements of test trial completion of several new vaccines resulted in the launching of immunization for the common person around the globe highlighting a ray of hope to cope with this infection. Meanwhile, genetic variations in SARS-CoV-2 and third layer of infection spread in numerous countries emerged as a stronger prototype than the parental. New and parental SARS-CoV-2 strains appeared as a risk factor for other pre-existing diseases like cancer, diabetes, neurological disorders, kidney, liver, heart, and eye injury. This situation requires more attention and re-structuring of the currently developed vaccines and/or drugs against SARS-CoV-2 infection. Although a decline in COVID-19 infection has been reported globally, an increase in COVID-19 cases in the subcontinent and east Mediterranean area could be alarming. In this review, we have summarized the current information about the SARS-CoV-2 biology, its interaction and possible infection pathways within the host, epidemiology, risk factors, economic collapse, and possible vaccine and drug development.
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Affiliation(s)
- Waqar Ahmad
- Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
- The University of Queensland, Brisbane, Australia
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Shademan B, Nourazarian A, Hajazimian S, Isazadeh A, Biray Avci C, Oskouee MA. CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2. Front Mol Biosci 2022; 8:772788. [PMID: 35087864 PMCID: PMC8787289 DOI: 10.3389/fmolb.2021.772788] [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: 09/08/2021] [Accepted: 12/21/2021] [Indexed: 01/08/2023] Open
Abstract
Outbreak and rapid spread of coronavirus disease (COVID-19) caused by coronavirus acute respiratory syndrome (SARS-CoV-2) caused severe acute respiratory syndrome (SARS-CoV-2) that started in Wuhan, and has become a global problem because of the high rate of human-to-human transmission and severe respiratory infections. Because of high prevalence of SARS-CoV-2, which threatens many people worldwide, rapid diagnosis and simple treatment are needed. Genome editing is a nucleic acid-based approach to altering the genome by artificially changes in genetic information and induce irreversible changes in the function of target gene. Clustered, regularly interspaced short palindromic repeats (CRISPR/Cas) could be a practical and straightforward approach to this disease. CRISPR/Cas system contains Cas protein, which is controlled by a small RNA molecule to create a double-stranded DNA gap. Evidence suggested that CRISPR/Cas was also usable for diagnosis and treatment of SARS-CoV-2 infection. In this review study, we discoursed on application of CRISPR technology in detection and treatment of SARS-CoV-2 infection. Another aspect of this study was to introduce potential future problems in use of CRISPR/Cas technology.
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Affiliation(s)
- Behrouz Shademan
- Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Alireza Nourazarian
- Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran
| | - Saba Hajazimian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Isazadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Cigir Biray Avci
- Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Mahin Ahangar Oskouee
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Essentials of COVID-19 and treatment approaches. DATA SCIENCE FOR COVID-19 2022. [PMCID: PMC8988944 DOI: 10.1016/b978-0-323-90769-9.00026-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The coronavirus family is as old as the 1930s when it first showed symptoms in chicken. The virus thereafter kept evolving and it has significantly taken over a large percentage of people worldwide in the form of this new pandemic. As of the present day, there is no treatment available for coronavirus disease 2019 (COVID-19) (caused by the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), although supportive therapy and preventive measures have shown a tremendous control rate among certain patients. Drugs like remdesivir, camostat, nafamostat, ritonavir/lopinavir, several monoclonal antibodies, and CPs are in their early phases of trials. There are approved by the WHO under an emergency use authorization program. Favipiravir has entered its phase 3 clinical trial and is supported by evidence to show no or less adverse effects in patients infected with SARS-CoV-2. Vaccine development is accelerating its pace, and vaccines will probably become available by the end of the year 2020.
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Salem R, El-Kholy AA, Waly FR, Ayman D, Sakr A, Hussein M. Generation and utility of a single-chain fragment variable monoclonal antibody platform against a baculovirus expressed recombinant receptor binding domain of SARS-CoV-2 spike protein. Mol Immunol 2021; 141:287-296. [PMID: 34915268 PMCID: PMC8660258 DOI: 10.1016/j.molimm.2021.12.006] [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: 11/14/2021] [Revised: 12/01/2021] [Accepted: 12/05/2021] [Indexed: 02/08/2023]
Abstract
As the second wave of COVID-19 launched, various variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have emerged with a dramatic global spread amongst millions of people causing unprecedented case fatalities and economic shut-downs. That initiated a necessity for developing specific diagnostics and therapeutics along with vaccines to control such a pandemic. This endeavor describes generation of murine derived recombinant single-chain fragment variable (scFv) as a monoclonal antibody (MAb) platform targeting the receptor binding domain (RBD) of Spike protein of SARS-CoV-2. A specific synthesized RBD coding sequence was cloned and expressed in Baculovirus expression system. The recombinant RBD (rRBD) was ascertained to be at the proper encoding size of ∼ 600bp and expressed protein of the molecular weight of ∼ 21KDa. Purified rRBD was proved genuinely antigenic and immunogenic, exhibiting specific reactivity to anti-SARS-CoV-2 antibody in an indirect enzyme-linked immunosorbent assay (ELISA), and inducing strong seroconversion in immunized mice. The scFv phage display library against rRBD was successfully constructed, revealing ∼ 90 % recombination frequency, and great enriching factor reaching 88 % and 25 % in polyclonal Ab-based and MAb-based ELISAs, respectively. Typically, three unique scFvs were generated, selected, purified and molecularly identified. That was manifested by their: accurate structure, close relation to the mouse immunoglobulin (Ig) superfamily, right anchored six complementarily-determining regions (CDRs) as three within variable heavy (vH) and variable light (vL) regions each, and proper configuration of the three-dimensional (3D) structure. Besides, their expression downstream in a non-suppressive amber codon of E. coli strain SS32 created a distinct protein band at an apparent molecular weight of ∼ 27KDa. Moreover, the purified scFvs showed authentic immunoreactivity and specificity to both rRBD and SARS-CoV-2 in western blot and ELISA. Accordingly, these developed scFvs platform might be a functional candidate for research, inexpensive diagnostics and therapeutics, mitigating spread of COVID-19.
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Affiliation(s)
- Reda Salem
- Agricultural Genetic Engineering Research Institute (AGERI), ARC, 12619, Giza, Egypt.
| | - Alaa A El-Kholy
- Veterinary Sera and Vaccines Research Institute (VSVRI), ARC, Abbassia, P.O. Box #131, 11381, Cairo, Egypt
| | - Fatma R Waly
- Agricultural Genetic Engineering Research Institute (AGERI), ARC, 12619, Giza, Egypt
| | - Dalia Ayman
- Agricultural Genetic Engineering Research Institute (AGERI), ARC, 12619, Giza, Egypt
| | - Aya Sakr
- Agricultural Genetic Engineering Research Institute (AGERI), ARC, 12619, Giza, Egypt
| | - Mai Hussein
- Agricultural Genetic Engineering Research Institute (AGERI), ARC, 12619, Giza, Egypt
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Han F, Liu Y, Mo M, Chen J, Wang C, Yang Y, Wu J. Current treatment strategies for COVID‑19 (Review). Mol Med Rep 2021; 24:858. [PMID: 34664677 PMCID: PMC8548951 DOI: 10.3892/mmr.2021.12498] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/25/2021] [Indexed: 12/17/2022] Open
Abstract
The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID‑19). To date, there is no specific therapy established to treat COVID‑19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS‑CoV‑2 in humans. For the present review, >100 publications on therapeutic agents for COVID‑19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta‑analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS‑CoV‑2 infection were highlighted. Since the outbreak of COVID‑19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID‑19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID‑19. The molecular mechanisms of these therapeutic agents against SARS‑CoV2 have been investigated, including inhibition of viral interactions with angiotensin‑converting enzyme 2 receptors in human cells, viral RNA‑dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID‑19 were acknowledged.
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Affiliation(s)
- Fabin Han
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
- Laboratory for Stem Cell and Regenerative Medicine, Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital/Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Yanming Liu
- Laboratory for Stem Cell and Regenerative Medicine, Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital/Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Mei Mo
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Juanli Chen
- Laboratory for Stem Cell and Regenerative Medicine, Institute for Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital/Liaocheng University, Liaocheng, Shandong 252000, P.R. China
| | - Cheng Wang
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
- Department of Research and Development, Shandong Meijia Therapeutic Biotechnology Co., Ltd., Jinan, Shandong 250100, P.R. China
| | - Yong Yang
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
| | - Jibiao Wu
- The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovation Institute for Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
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Morales-Núñez JJ, Muñoz-Valle JF, Torres-Hernández PC, Hernández-Bello J. Overview of Neutralizing Antibodies and Their Potential in COVID-19. Vaccines (Basel) 2021; 9:vaccines9121376. [PMID: 34960121 PMCID: PMC8706198 DOI: 10.3390/vaccines9121376] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/12/2021] [Accepted: 11/20/2021] [Indexed: 01/08/2023] Open
Abstract
The antibody response to respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major focus of COVID-19 research due to its clinical relevance and importance in vaccine and therapeutic development. Neutralizing antibody (NAb) evaluations are useful for the determination of individual or herd immunity against SARS-CoV-2, vaccine efficacy, and humoral protective response longevity, as well as supporting donor selection criteria for convalescent plasma therapy. In the current manuscript, we review the essential concepts of NAbs, examining their concept, mechanisms of action, production, and the techniques used for their detection; as well as presenting an overview of the clinical use of antibodies in COVID-19.
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Affiliation(s)
- José Javier Morales-Núñez
- Institute of Research in Biomedical Sciences, University Center of Health Sciences (CUCS), University of Guadalajara, Guadalajara 44340, Mexico; (J.J.M.-N.); (J.F.M.-V.)
| | - José Francisco Muñoz-Valle
- Institute of Research in Biomedical Sciences, University Center of Health Sciences (CUCS), University of Guadalajara, Guadalajara 44340, Mexico; (J.J.M.-N.); (J.F.M.-V.)
| | | | - Jorge Hernández-Bello
- Institute of Research in Biomedical Sciences, University Center of Health Sciences (CUCS), University of Guadalajara, Guadalajara 44340, Mexico; (J.J.M.-N.); (J.F.M.-V.)
- Correspondence: ; Tel.: +52-333-450-9355
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Bhat V, Chavan P, Khattry N, Gupta S. Dynamics of viral RNA load, virus culture, seroconversion & infectivity in COVID-19 patients: Implications on isolation policy. Indian J Med Res 2021; 153:585-590. [PMID: 34414920 PMCID: PMC8555608 DOI: 10.4103/ijmr.ijmr_3564_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The ongoing SARS-CoV-2 pandemic has spread all over the world due to rapid person-to-person transmission. More information about viral load dynamics and replication is needed for clarity on duration of infectiousness of an individual, along with its implications on transmission. This is important to healthcare facilities and public health authorities in formulating guidance on the duration of isolation for patients and return to work criteria for healthcare workers. The duration of detection of viral RNA by molecular methods in the upper respiratory tract has ranged from 2 to 12 wk. Viral RNA detection by reverse transcription polymerase chain reaction (RT-PCR) does not necessarily mean that the individual is infectious to others, as the detected virus may not be replication competent. Infectious virus is generally not shed beyond 20 days of the onset of symptoms in most patients, including severely ill and immunocompromised, as indicated by failure to isolate replication-competent virus beyond this timeline in available studies. Further, detection of neutralizing antibodies in the serum, although associated with positive RT-PCR, is generally not associated with infectious virus shedding as indicated by negative viral cultures beyond this period. In this review, we analyze the current literature on the dynamics of viral load, culture, seroconversion and their implications on infectivity and the duration of isolation precautions for COVID-19 patients.
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Affiliation(s)
- Vivek Bhat
- Department of Microbiology, Advanced Centre for Treatment, Research & Education, Tata Memorial Centre, Homi Bhaba National Institute, Navi Mumbai, Maharashtra, India
| | - Preeti Chavan
- Department of Composite Laboratory, Advanced Centre for Treatment, Research & Education, Tata Memorial Centre, Homi Bhaba National Institute, Navi Mumbai, Maharashtra, India
| | - Navin Khattry
- Department of Medical Oncology, Advanced Centre for Treatment, Research & Education, Tata Memorial Centre, Homi Bhaba National Institute, Navi Mumbai, Maharashtra, India
| | - Sudeep Gupta
- Department of Medical Oncology, Advanced Centre for Treatment, Research & Education, Tata Memorial Centre, Homi Bhaba National Institute, Navi Mumbai, Maharashtra, India
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IgG Study of Blood Sera of Patients with COVID-19. Pathogens 2021; 10:pathogens10111421. [PMID: 34832577 PMCID: PMC8621046 DOI: 10.3390/pathogens10111421] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 10/22/2021] [Accepted: 10/30/2021] [Indexed: 12/16/2022] Open
Abstract
The COVID-19 pandemic, which began at the end of 2019 in Wuhan, has affected 220 countries and territories to date. In the present study, we studied humoral immunity in samples of the blood sera of COVID-19 convalescents of varying severity and patients who died due to this infection, using native SARS-CoV-2 and its individual recombinant proteins. The cross-reactivity with SARS-CoV (2002) was also assessed. We used infectious and inactivated SARS-CoV-2/human/RUS/Nsk-FRCFTM-1/2020 strain, inactivated SARS-CoV strain (strain Frankfurt 1, 2002), recombinant proteins, and blood sera of patients diagnosed with COVID-19. The blood sera from patients were analyzed by the Virus Neutralization test, Immunoblotting, and ELISA. The median values and mean ± SD of titers of specific and cross-reactive antibodies in blood sera tested in ELISA were mainly distributed in the following descending order: N > trimer S > RBD. ELISA and immunoblotting revealed a high cross-activity of antibodies specific to SARS-CoV-2 with the SARS-CoV antigen (2002), mainly with the N protein. The presence of antibodies specific to RBD corresponds with the data on the neutralizing activity of blood sera. According to the neutralization test in a number of cases, higher levels of antibodies that neutralize SARS-CoV-2 were detected in blood serum taken from patients several days before their death than in convalescents with a ranging disease severity. This high level of neutralizing antibodies specific to SARS-CoV-2 in the blood sera of patients who subsequently died in hospital from COVID-19 requires a thorough study of the role of humoral immunity as well as comorbidity and other factors affecting the humoral response in this disease.
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Najmeddin A, Bahrololoumi Shapourabadi M, Behdani M, Dorkoosh F. Nanobodies as powerful pulmonary targeted biotherapeutics against SARS-CoV-2, pharmaceutical point of view. Biochim Biophys Acta Gen Subj 2021; 1865:129974. [PMID: 34343644 PMCID: PMC8325376 DOI: 10.1016/j.bbagen.2021.129974] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 07/23/2021] [Accepted: 07/28/2021] [Indexed: 12/16/2022]
Abstract
Background Since December 2019, the newly emerged SARS-CoV-2 virus continues to infect humans and many people died from severe Covid-19 during the last 2 years worldwide. Different approaches are being used for treatment of this infection and its consequences, but limited results have been achieved and new therapeutics are still needed. One of the most interesting biotherapeutics in this era are Nanobodies which have shown very promising results in recent researches. Scope of review Here, we have reviewed the potentials of Nanobodies in Covid-19 treatment. We have also discussed the properties of these biotherapeutics that make them very suitable for pulmonary drug delivery, which seems to be very important route of administration in this disease. Major conclusion Nanobodies with their special biological and biophysical characteristics and their resistance against harsh manufacturing condition, can be considered as promising, targeted biotherapeutics which can be administered by pulmonary delivery pharmaceutical systems against Covid-19. General significance Covid-19 has become a global problem during the last two years and with emerging mutant strains, prophylactic and therapeutic approaches are still highly needed. Nanobodies with their specific properties can be considered as valuable and promising candidates in Covid-19 therapy.
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Affiliation(s)
- Ali Najmeddin
- Department of Pharmaceutics, Faculty of pharmacy, Tehran University of Medical Sciences, Iran.
| | | | - Mahdi Behdani
- Venom and Biotherapeutic Molecules Lab, Biotechnology Research Centre, Pasteur Institute of Iran, Tehran, Iran.
| | - Farid Dorkoosh
- Department of Pharmaceutics, Faculty of pharmacy, Tehran University of Medical Sciences, Iran; Medical Biomaterial Research Center (MBRC), Tehran University of Medical Sciences, Iran.
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Tayeb HH, Felimban R, Almaghrabi S, Hasaballah N. Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks. COLLOID AND INTERFACE SCIENCE COMMUNICATIONS 2021; 45:100533. [PMID: 34692429 PMCID: PMC8526445 DOI: 10.1016/j.colcom.2021.100533] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 10/07/2021] [Accepted: 10/14/2021] [Indexed: 05/08/2023]
Abstract
Viral diseases are emerging as global threats. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), that causes coronavirus disease (COVID-19), has severe global impacts. Safety, dosage, and potency of vaccines recently approved for emergency use against SARS-CoV-2 need further evaluation. There is still no effective treatment against COVID-19; therefore, safe, and effective vaccines or therapeutics against SARS-CoV-2 are urgently needed. Oil-in-water nanoemulsions (O/W NEs) are emerging as sophisticated, protective, and therapeutic platforms. Encapsulation capacity, which offers better drug pharmacokinetics, coupled with the tunable surfaces present NEs as promising tools for pharmaceutical applications. The challenges facing drug discovery, and the advancements of NEs in drug delivery demonstrate the potential of NEs against evolving diseases, like COVID-19. Here we summarize current COVID-19 knowledge and discuss the composition, stability, preparation, characterization, and biological fate of O/W NEs. We also provide insights into NE structural-functional properties that may contribute to therapeutic or preventative solutions against COVID-19.
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Affiliation(s)
- Hossam H Tayeb
- Nanomedicine Unit, Center of Innovations in Personalized Medicine (CIPM), King Abdulaziz University, 21589 Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Raed Felimban
- 3D Bioprinting Unit, Center of Innovations in Personalized Medicine (CIPM), King Abdulaziz University, 21589 Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Sarah Almaghrabi
- Nanomedicine Unit, Center of Innovations in Personalized Medicine (CIPM), King Abdulaziz University, 21589 Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
| | - Nojod Hasaballah
- Nanomedicine Unit, Center of Innovations in Personalized Medicine (CIPM), King Abdulaziz University, 21589 Jeddah, Saudi Arabia
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Macip G, Garcia-Segura P, Mestres-Truyol J, Saldivar-Espinoza B, Ojeda-Montes MJ, Gimeno A, Cereto-Massagué A, Garcia-Vallvé S, Pujadas G. Haste makes waste: A critical review of docking-based virtual screening in drug repurposing for SARS-CoV-2 main protease (M-pro) inhibition. Med Res Rev 2021; 42:744-769. [PMID: 34697818 PMCID: PMC8662214 DOI: 10.1002/med.21862] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/30/2021] [Accepted: 10/11/2021] [Indexed: 12/23/2022]
Abstract
This review makes a critical evaluation of 61 peer‐reviewed manuscripts that use a docking step in a virtual screening (VS) protocol to predict SARS‐CoV‐2 M‐pro (M‐pro) inhibitors in approved or investigational drugs. Various manuscripts predict different compounds, even when they use a similar initial dataset and methodology, and most of them do not validate their methodology or results. In addition, a set of known 150 SARS‐CoV‐2 M‐pro inhibitors extracted from the literature and a second set of 81 M‐pro inhibitors and 113 inactive compounds obtained from the COVID Moonshot project were used to evaluate the reliability of using docking scores as feasible predictors of the potency of a SARS‐CoV‐2 M‐pro inhibitor. Using two SARS‐CoV‐2 M‐pro structures and five protein‐ligand docking programs, we proved that the correlation between the pIC50 and docking scores is not good. Neither was any correlation found between the pIC50 and the ∆G calculated with an MM‐GBSA method. When a group of experimentally known inactive compounds was added, neither the docking scores or the ∆G were able to distinguish between compounds with or without M‐pro experimental inhibitory activity. Performances improved when covalent and noncovalent inhibitors were treated separately, but were not good enough to fully support using a docking score as a cutoff value for selecting new putative M‐pro inhibitors or predicting the relative bioactivity of a compound by comparison with a reference compound. The two sets of known SARS‐CoV‐2 M‐pro inhibitors presented here could be used for validating future VS protocols which aim to predict M‐pro inhibitors.
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Affiliation(s)
- Guillem Macip
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Research group in Cheminformatics & Nutrition, Tarragona, Tarragona, Spain
| | - Pol Garcia-Segura
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Research group in Cheminformatics & Nutrition, Tarragona, Tarragona, Spain
| | - Júlia Mestres-Truyol
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Research group in Cheminformatics & Nutrition, Tarragona, Tarragona, Spain
| | - Bryan Saldivar-Espinoza
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Research group in Cheminformatics & Nutrition, Tarragona, Tarragona, Spain
| | | | - Aleix Gimeno
- Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Adrià Cereto-Massagué
- EURECAT Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), Reus, Spain
| | - Santiago Garcia-Vallvé
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Research group in Cheminformatics & Nutrition, Tarragona, Tarragona, Spain.,EURECAT, TECNIO, CEICS, Avinguda Universitat 1, Reus, Spain
| | - Gerard Pujadas
- Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Research group in Cheminformatics & Nutrition, Tarragona, Tarragona, Spain.,EURECAT, TECNIO, CEICS, Avinguda Universitat 1, Reus, Spain
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Generation and persistence of S1 IgG and neutralizing antibodies in post-COVID-19 patients. Infection 2021; 50:447-456. [PMID: 34668145 PMCID: PMC8525617 DOI: 10.1007/s15010-021-01705-7] [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: 06/09/2021] [Accepted: 09/22/2021] [Indexed: 11/01/2022]
Abstract
BACKGROUND Antibody-mediated immune response plays an important role in protection against reinfection. In the case of SARS-CoV-2 infection, the maximum duration of antibody response is still unknown. In this work, the generation of neutralizing antibodies (NAbs) and IgG antibodies against the S1 subunit (S1 IgG ) of SARS-CoV-2 and their possible duration were determined through decay models. METHODS 132 participants with SARS-CoV-2 infection were classified according to the severity of the disease. Seroconversion and persistence of S1 IgG antibodies and NAbs were determined by ELISA, samples were taken at two different times post-infection and duration of those antibodies was estimated using Linear Mixed Models (LMMs). RESULTS The highest amount of S1 IgGs antibodies was associated with age (41 years or older), greater severity of COVID-19 and male gender. NAbs production was associated with the same variables, except for age. The percentage of NAbs decay is higher in the asymptomatic group (P = 0.033), while in S1 IgG antibodies decay, no statistical difference was found between the 4 severity groups. An exponential decay model was built by using a LMM and similarly, two dispersion regions where constructed. The duration of S1 IgG antibodies was 744 days (668-781) for first region and 744 days (453-1231) for the second. Regarding NAbs, an adaptative LMM was used to model a logistic function, determining a duration of 267 days (215-347). CONCLUSION Humoral immunity to SARS-CoV-2 infection depends on the severity of the disease, gender and age. This immune response could be long-lasting as for other coronaviruses.
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