HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility
BackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (h...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1008463/full |
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| author | Mohammed Y. Behairy Mohamed A. Soltan Muhammad Alaa Eldeen Jawaher A. Abdulhakim Maryam M. Alnoman Mohamed M. Abdel-Daim Mohamed M. Abdel-Daim Hassan Otifi Saleh M. Al-Qahtani Mohamed Samir A. Zaki Mohamed Samir A. Zaki Ghadi Alsharif Sarah Albogami Ibrahim Jafri Eman Fayad Khaled M. Darwish Sameh S. Elhady Refaat A. Eid |
| author_facet | Mohammed Y. Behairy Mohamed A. Soltan Muhammad Alaa Eldeen Jawaher A. Abdulhakim Maryam M. Alnoman Mohamed M. Abdel-Daim Mohamed M. Abdel-Daim Hassan Otifi Saleh M. Al-Qahtani Mohamed Samir A. Zaki Mohamed Samir A. Zaki Ghadi Alsharif Sarah Albogami Ibrahim Jafri Eman Fayad Khaled M. Darwish Sameh S. Elhady Refaat A. Eid |
| author_sort | Mohammed Y. Behairy |
| collection | DOAJ |
| description | BackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19.MethodsWe conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations.ResultsThe comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation.ConclusionsThe presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease. |
| first_indexed | 2024-04-10T15:55:26Z |
| format | Article |
| id | doaj.art-dc702d173f2045cbb1afcafa74927126 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T15:55:26Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dc702d173f2045cbb1afcafa749271262023-02-10T14:38:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10084631008463HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibilityMohammed Y. Behairy0Mohamed A. Soltan1Muhammad Alaa Eldeen2Jawaher A. Abdulhakim3Maryam M. Alnoman4Mohamed M. Abdel-Daim5Mohamed M. Abdel-Daim6Hassan Otifi7Saleh M. Al-Qahtani8Mohamed Samir A. Zaki9Mohamed Samir A. Zaki10Ghadi Alsharif11Sarah Albogami12Ibrahim Jafri13Eman Fayad14Khaled M. Darwish15Sameh S. Elhady16Refaat A. Eid17Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City, Sadat City, EgyptDepartment of Microbiology and immunology, Faculty of Pharmacy, Sinai University – Kantara Branch, Ismailia, EgyptCell Biology, Histology & Genetics Division, Biology Department, Faculty of Science, Zagazig University, Zagazig, EgyptMedical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi ArabiaBiology Department, Faculty of Science, Taibah University, Yanbu, Saudi ArabiaDepartment of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi ArabiaPharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, EgyptPathology Department, College of Medicine, King Khalid University, Abha, Saudi ArabiaDepartment of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia0Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia1Department of Histology and Cell Biology, College of Medicine, Zagazig University, Zagazig, Egypt2College of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia3Department of Biotechnology, College of Sciences, Taif University, Taif, Saudi Arabia3Department of Biotechnology, College of Sciences, Taif University, Taif, Saudi Arabia3Department of Biotechnology, College of Sciences, Taif University, Taif, Saudi Arabia4Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt5Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaPathology Department, College of Medicine, King Khalid University, Abha, Saudi ArabiaBackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19.MethodsWe conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations.ResultsThe comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation.ConclusionsThe presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1008463/fullCOVID-19SNPsmolecular dynamicsantimicrobial peptideshBD-2 |
| spellingShingle | Mohammed Y. Behairy Mohamed A. Soltan Muhammad Alaa Eldeen Jawaher A. Abdulhakim Maryam M. Alnoman Mohamed M. Abdel-Daim Mohamed M. Abdel-Daim Hassan Otifi Saleh M. Al-Qahtani Mohamed Samir A. Zaki Mohamed Samir A. Zaki Ghadi Alsharif Sarah Albogami Ibrahim Jafri Eman Fayad Khaled M. Darwish Sameh S. Elhady Refaat A. Eid HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility Frontiers in Immunology COVID-19 SNPs molecular dynamics antimicrobial peptides hBD-2 |
| title | HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility |
| title_full | HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility |
| title_fullStr | HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility |
| title_full_unstemmed | HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility |
| title_short | HBD-2 variants and SARS-CoV-2: New insights into inter-individual susceptibility |
| title_sort | hbd 2 variants and sars cov 2 new insights into inter individual susceptibility |
| topic | COVID-19 SNPs molecular dynamics antimicrobial peptides hBD-2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1008463/full |
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