Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations
Abstract The high magnitude zoonotic event has caused by Severe Acute Respitarory Syndrome CoronaVirus-2 (SARS-CoV-2) is Coronavirus Disease-2019 (COVID-19) epidemics. This disease has high rate of spreading than mortality in humans. The human receptor, Angiotensin-Converting Enzyme 2 (ACE2), is the...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-20773-9 |
| _version_ | 1811165999199682560 |
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| author | Pawan Kumar Raghav Aditya Raghav Anjali Lathwal Archit Saxena Zoya Mann Manisha Sengar Raja Rajalingam |
| author_facet | Pawan Kumar Raghav Aditya Raghav Anjali Lathwal Archit Saxena Zoya Mann Manisha Sengar Raja Rajalingam |
| author_sort | Pawan Kumar Raghav |
| collection | DOAJ |
| description | Abstract The high magnitude zoonotic event has caused by Severe Acute Respitarory Syndrome CoronaVirus-2 (SARS-CoV-2) is Coronavirus Disease-2019 (COVID-19) epidemics. This disease has high rate of spreading than mortality in humans. The human receptor, Angiotensin-Converting Enzyme 2 (ACE2), is the leading target site for viral Spike-protein (S-protein) that function as binding ligands and are responsible for their entry in humans. The patients infected with COVID-19 with comorbidities, particularly cancer patients, have a severe effect or high mortality rate because of the suppressed immune system. Nevertheless, there might be a chance wherein cancer patients cannot be infected with SARS-CoV-2 because of mutations in the ACE2, which may be resistant to the spillover between species. This study aimed to determine the mutations in the sequence of the human ACE2 protein and its dissociation with SARS-CoV-2 that might be rejecting viral transmission. The in silico approaches were performed to identify the impact of SARS-CoV-2 S-protein with ACE2 mutations, validated experimentally, occurred in the patient, and reported in cell lines. The identified changes significantly affect SARS-CoV-2 S-protein interaction with ACE2, demonstrating the reduction in the binding affinity compared to SARS-CoV. The data presented in this study suggest ACE2 mutants have a higher and lower affinity with SARS-Cov-2 S-protein to the wild-type human ACE2 receptor. This study would likely be used to report SARS-CoV-2 resistant ACE2 mutations and can be used to design active peptide development to inactivate the viral spread of SARS-CoV-2 in humans. |
| first_indexed | 2024-04-10T15:45:15Z |
| format | Article |
| id | doaj.art-57e963dc2edf4a8081a55ed9334264be |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T15:45:15Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-57e963dc2edf4a8081a55ed9334264be2023-02-12T12:09:09ZengNature PortfolioScientific Reports2045-23222023-02-0113114310.1038/s41598-022-20773-9Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutationsPawan Kumar Raghav0Aditya Raghav1Anjali Lathwal2Archit Saxena3Zoya Mann4Manisha Sengar5Raja Rajalingam6Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San FranciscoBioExInDepartment of Computational Biology, Indraprastha Institute of Information TechnologyAmity Institute of Biotechnology, Amity UniversityBioExInDepartment of Zoology, Deshbandhu College, University of DelhiImmunogenetics and Transplantation Laboratory, Department of Surgery, University of California San FranciscoAbstract The high magnitude zoonotic event has caused by Severe Acute Respitarory Syndrome CoronaVirus-2 (SARS-CoV-2) is Coronavirus Disease-2019 (COVID-19) epidemics. This disease has high rate of spreading than mortality in humans. The human receptor, Angiotensin-Converting Enzyme 2 (ACE2), is the leading target site for viral Spike-protein (S-protein) that function as binding ligands and are responsible for their entry in humans. The patients infected with COVID-19 with comorbidities, particularly cancer patients, have a severe effect or high mortality rate because of the suppressed immune system. Nevertheless, there might be a chance wherein cancer patients cannot be infected with SARS-CoV-2 because of mutations in the ACE2, which may be resistant to the spillover between species. This study aimed to determine the mutations in the sequence of the human ACE2 protein and its dissociation with SARS-CoV-2 that might be rejecting viral transmission. The in silico approaches were performed to identify the impact of SARS-CoV-2 S-protein with ACE2 mutations, validated experimentally, occurred in the patient, and reported in cell lines. The identified changes significantly affect SARS-CoV-2 S-protein interaction with ACE2, demonstrating the reduction in the binding affinity compared to SARS-CoV. The data presented in this study suggest ACE2 mutants have a higher and lower affinity with SARS-Cov-2 S-protein to the wild-type human ACE2 receptor. This study would likely be used to report SARS-CoV-2 resistant ACE2 mutations and can be used to design active peptide development to inactivate the viral spread of SARS-CoV-2 in humans.https://doi.org/10.1038/s41598-022-20773-9 |
| spellingShingle | Pawan Kumar Raghav Aditya Raghav Anjali Lathwal Archit Saxena Zoya Mann Manisha Sengar Raja Rajalingam Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations Scientific Reports |
| title | Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations |
| title_full | Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations |
| title_fullStr | Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations |
| title_full_unstemmed | Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations |
| title_short | Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations |
| title_sort | experimental and clinical data analysis for identification of covid 19 resistant ace2 mutations |
| url | https://doi.org/10.1038/s41598-022-20773-9 |
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