Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, no...

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Main Authors: Mohamed A. A. Hussein, Hosni A. M. Hussein, Ali A. Thabet, Karim M. Selim, Mervat A. Dawood, Ahmed M. El-Adly, Ahmed A. Wardany, Ali Sobhy, Sameh Magdeldin, Aya Osama, Ali M. Anwar, Mohammed Abdel-Wahab, Hussam Askar, Elsayed K. Bakhiet, Serageldeen Sultan, Amgad A. Ezzat, Usama Abdel Raouf, Magdy M. Afifi
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/11/9/1408
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author Mohamed A. A. Hussein
Hosni A. M. Hussein
Ali A. Thabet
Karim M. Selim
Mervat A. Dawood
Ahmed M. El-Adly
Ahmed A. Wardany
Ali Sobhy
Sameh Magdeldin
Aya Osama
Ali M. Anwar
Mohammed Abdel-Wahab
Hussam Askar
Elsayed K. Bakhiet
Serageldeen Sultan
Amgad A. Ezzat
Usama Abdel Raouf
Magdy M. Afifi
author_facet Mohamed A. A. Hussein
Hosni A. M. Hussein
Ali A. Thabet
Karim M. Selim
Mervat A. Dawood
Ahmed M. El-Adly
Ahmed A. Wardany
Ali Sobhy
Sameh Magdeldin
Aya Osama
Ali M. Anwar
Mohammed Abdel-Wahab
Hussam Askar
Elsayed K. Bakhiet
Serageldeen Sultan
Amgad A. Ezzat
Usama Abdel Raouf
Magdy M. Afifi
author_sort Mohamed A. A. Hussein
collection DOAJ
description Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton’s jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and <i>in ovo</i>. The half-maximal inhibitory concentrations (IC<sub>50</sub>), cytotoxic concentration (CC<sub>50</sub>), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC<sub>50</sub> and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC<sub>50</sub> and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the <i>in ovo</i> model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.
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spelling doaj.art-75debe90b3094b99979a1921efa6baef2023-11-23T07:58:48ZengMDPI AGCells2073-44092022-04-01119140810.3390/cells11091408Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis CoronavirusesMohamed A. A. Hussein0Hosni A. M. Hussein1Ali A. Thabet2Karim M. Selim3Mervat A. Dawood4Ahmed M. El-Adly5Ahmed A. Wardany6Ali Sobhy7Sameh Magdeldin8Aya Osama9Ali M. Anwar10Mohammed Abdel-Wahab11Hussam Askar12Elsayed K. Bakhiet13Serageldeen Sultan14Amgad A. Ezzat15Usama Abdel Raouf16Magdy M. Afifi17Department of Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Zoology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptReference Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Agricultural Research Center, Dokki, Giza 12618, EgyptClinical Pathology, Mansoura Research Center for Cord Stem Cells (MARC-CSC), Faculty of Medicine, Mansoura University, El Mansoura 35516, EgyptDepartment of Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Assiut 71524, EgyptProteomics and Metabolomics Research Program, Basic Research Department, Children’s Cancer Hospital, (CCHE-57357), Cairo 57357, EgyptProteomics and Metabolomics Research Program, Basic Research Department, Children’s Cancer Hospital, (CCHE-57357), Cairo 57357, EgyptProteomics and Metabolomics Research Program, Basic Research Department, Children’s Cancer Hospital, (CCHE-57357), Cairo 57357, EgyptDepartment of Zoology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Zoology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptDepartment of Microbiology, Virology Division, Faculty of Veterinary Medicine, South Valley University, Qena 83523, EgyptDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Al-Azhar University, Assiut 71524, EgyptDepartment of Botany and Microbiology, Faculty of Science, Aswan University, Aswan 81528, EgyptDepartment of Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, EgyptHuman SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton’s jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and <i>in ovo</i>. The half-maximal inhibitory concentrations (IC<sub>50</sub>), cytotoxic concentration (CC<sub>50</sub>), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC<sub>50</sub> and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC<sub>50</sub> and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the <i>in ovo</i> model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.https://www.mdpi.com/2073-4409/11/9/1408severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infectious bronchitis virus (IBV)Wharton’s jelly stem cellssecretomecoronaviruses
spellingShingle Mohamed A. A. Hussein
Hosni A. M. Hussein
Ali A. Thabet
Karim M. Selim
Mervat A. Dawood
Ahmed M. El-Adly
Ahmed A. Wardany
Ali Sobhy
Sameh Magdeldin
Aya Osama
Ali M. Anwar
Mohammed Abdel-Wahab
Hussam Askar
Elsayed K. Bakhiet
Serageldeen Sultan
Amgad A. Ezzat
Usama Abdel Raouf
Magdy M. Afifi
Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses
Cells
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infectious bronchitis virus (IBV)
Wharton’s jelly stem cells
secretome
coronaviruses
title Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses
title_full Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses
title_fullStr Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses
title_full_unstemmed Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses
title_short Human Wharton’s Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses
title_sort human wharton s jelly mesenchymal stem cells secretome inhibits human sars cov 2 and avian infectious bronchitis coronaviruses
topic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infectious bronchitis virus (IBV)
Wharton’s jelly stem cells
secretome
coronaviruses
url https://www.mdpi.com/2073-4409/11/9/1408
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