Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus
The emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrug-resistant forms of the disease are prevalent, and there is currently no licensed commercial...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022159/full |
| _version_ | 1828335613361782784 |
|---|---|
| author | Alhumaidi B. Alabbas |
| author_facet | Alhumaidi B. Alabbas |
| author_sort | Alhumaidi B. Alabbas |
| collection | DOAJ |
| description | The emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrug-resistant forms of the disease are prevalent, and there is currently no licensed commercial vaccine. Due to the numerous limitations of experimental vaccines, vaccines against various bacterial and viral diseases have developed via computational vaccine design. Several subtractive proteomics, immunoinformatics, docking, and simulation approaches were used in this study to develop a multi-epitope–based vaccine against Sin Nombre orthohantavirus. One possible antigenic protein—the glycoprotein precursor of surface glycoproteins (accession number >AAC42202.1)—was selected as a candidate for B cell–derived T cell epitopes mapping the detailed analysis of the core genome. Among the predicted epitopes, four epitopes (QVDWTKKSST, GLAASPPHL, SSYSYRRKLV, and MESGWSDTA), which were probably antigenic, nonallergenic, nontoxic, and water soluble, were used in the multi-epitope vaccine’s construction. The shortlisted epitopes have the potency to cover 99.78% of the world’s population, 97.93% of the Chinese population, and 97.36% of the Indian population. The epitopes were connected through AAY linkers and joined with >50S ribosomal adjuvant to enhance their efficacy. The vaccine comprises 182 amino acids with a molecular weight of 19.03770 kDa and an instability index of 26.52, indicating that the protein is stable. A molecular docking study revealed that the vaccine has a good binding affinity with TLR-4 and TLR-8, which is vital for inducing the immune system. Top-1 docked complexes of vaccine- TLR-4 and TLR-8 with the lowest binding energy of -12.52 kc/mol and -5.42 kc/mol, respectively, were considered for molecular dynamic simulation analysis. Furthermore, we predicted that the docked complexes are properly stable throughout simulation time in both normal mode and AMBER-based simulation analysis. The MMGBSA analysis calculated -122.17 and -125.4 net binding energies for the TLR-8- and TLR4-vaccine complexes, respectively, while the MMPBSA analysis estimated -115.63 and -118.19 for the TLR-8- and TLR4-vaccine complex, respectively, confirming that the binding stability with receptors is stable, which is important for inducing a strong response. However, the current work is computation-based, so experimental validation is highly recommended. |
| first_indexed | 2024-04-13T21:49:47Z |
| format | Article |
| id | doaj.art-232f888ad6c542379551c5c5643cb320 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T21:49:47Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-232f888ad6c542379551c5c5643cb3202022-12-22T02:28:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10221591022159Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirusAlhumaidi B. AlabbasThe emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrug-resistant forms of the disease are prevalent, and there is currently no licensed commercial vaccine. Due to the numerous limitations of experimental vaccines, vaccines against various bacterial and viral diseases have developed via computational vaccine design. Several subtractive proteomics, immunoinformatics, docking, and simulation approaches were used in this study to develop a multi-epitope–based vaccine against Sin Nombre orthohantavirus. One possible antigenic protein—the glycoprotein precursor of surface glycoproteins (accession number >AAC42202.1)—was selected as a candidate for B cell–derived T cell epitopes mapping the detailed analysis of the core genome. Among the predicted epitopes, four epitopes (QVDWTKKSST, GLAASPPHL, SSYSYRRKLV, and MESGWSDTA), which were probably antigenic, nonallergenic, nontoxic, and water soluble, were used in the multi-epitope vaccine’s construction. The shortlisted epitopes have the potency to cover 99.78% of the world’s population, 97.93% of the Chinese population, and 97.36% of the Indian population. The epitopes were connected through AAY linkers and joined with >50S ribosomal adjuvant to enhance their efficacy. The vaccine comprises 182 amino acids with a molecular weight of 19.03770 kDa and an instability index of 26.52, indicating that the protein is stable. A molecular docking study revealed that the vaccine has a good binding affinity with TLR-4 and TLR-8, which is vital for inducing the immune system. Top-1 docked complexes of vaccine- TLR-4 and TLR-8 with the lowest binding energy of -12.52 kc/mol and -5.42 kc/mol, respectively, were considered for molecular dynamic simulation analysis. Furthermore, we predicted that the docked complexes are properly stable throughout simulation time in both normal mode and AMBER-based simulation analysis. The MMGBSA analysis calculated -122.17 and -125.4 net binding energies for the TLR-8- and TLR4-vaccine complexes, respectively, while the MMPBSA analysis estimated -115.63 and -118.19 for the TLR-8- and TLR4-vaccine complex, respectively, confirming that the binding stability with receptors is stable, which is important for inducing a strong response. However, the current work is computation-based, so experimental validation is highly recommended.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022159/fullhantavirusesSin Nombre orthohantavirusvaccinecomputational vaccinologybioinformatics |
| spellingShingle | Alhumaidi B. Alabbas Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus Frontiers in Immunology hantaviruses Sin Nombre orthohantavirus vaccine computational vaccinology bioinformatics |
| title | Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus |
| title_full | Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus |
| title_fullStr | Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus |
| title_full_unstemmed | Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus |
| title_short | Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus |
| title_sort | integrativesubtractive proteomics immunoinformatics docking and simulation approaches reveal candidate vaccine against sin nombre orthohantavirus |
| topic | hantaviruses Sin Nombre orthohantavirus vaccine computational vaccinology bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022159/full |
| work_keys_str_mv | AT alhumaidibalabbas integrativesubtractiveproteomicsimmunoinformaticsdockingandsimulationapproachesrevealcandidatevaccineagainstsinnombreorthohantavirus |