Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.
New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike posi...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-06-01
|
| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1012215 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850144963810033664 |
|---|---|
| author | Roberth Anthony Rojas Chávez Mohammad Fili Changze Han Syed A Rahman Isaiah G L Bicar Sullivan Gregory Annika Helverson Guiping Hu Benjamin W Darbro Jishnu Das Grant D Brown Hillel Haim |
| author_facet | Roberth Anthony Rojas Chávez Mohammad Fili Changze Han Syed A Rahman Isaiah G L Bicar Sullivan Gregory Annika Helverson Guiping Hu Benjamin W Darbro Jishnu Das Grant D Brown Hillel Haim |
| author_sort | Roberth Anthony Rojas Chávez |
| collection | DOAJ |
| description | New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. Here we show that SARS-CoV-2 lineages have distinct evolutionary spaces (a probabilistic definition of the sequence states that can be occupied by expanding virus subpopulations). This space can be accurately inferred from the patterns of amino acid variability at the whole-protein level. Robust networks of co-variable sites identify the highest-likelihood mutations in new VOC sublineages and predict remarkably well the emergence of subvariants with resistance mutations to COVID-19 therapeutics. Our studies reveal the contribution of low frequency variant patterns at heterologous sites across the protein to accurate prediction of the changes at each position of interest. |
| format | Article |
| id | doaj-art-830f0adf314c4501b60e2b80d32e8389 |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-830f0adf314c4501b60e2b80d32e83892025-08-20T02:28:12ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582024-06-01206e101221510.1371/journal.pcbi.1012215Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.Roberth Anthony Rojas ChávezMohammad FiliChangze HanSyed A RahmanIsaiah G L BicarSullivan GregoryAnnika HelversonGuiping HuBenjamin W DarbroJishnu DasGrant D BrownHillel HaimNew sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. Here we show that SARS-CoV-2 lineages have distinct evolutionary spaces (a probabilistic definition of the sequence states that can be occupied by expanding virus subpopulations). This space can be accurately inferred from the patterns of amino acid variability at the whole-protein level. Robust networks of co-variable sites identify the highest-likelihood mutations in new VOC sublineages and predict remarkably well the emergence of subvariants with resistance mutations to COVID-19 therapeutics. Our studies reveal the contribution of low frequency variant patterns at heterologous sites across the protein to accurate prediction of the changes at each position of interest.https://doi.org/10.1371/journal.pcbi.1012215 |
| spellingShingle | Roberth Anthony Rojas Chávez Mohammad Fili Changze Han Syed A Rahman Isaiah G L Bicar Sullivan Gregory Annika Helverson Guiping Hu Benjamin W Darbro Jishnu Das Grant D Brown Hillel Haim Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics. PLoS Computational Biology |
| title | Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics. |
| title_full | Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics. |
| title_fullStr | Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics. |
| title_full_unstemmed | Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics. |
| title_short | Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics. |
| title_sort | mapping the evolutionary space of sars cov 2 variants to anticipate emergence of subvariants resistant to covid 19 therapeutics |
| url | https://doi.org/10.1371/journal.pcbi.1012215 |
| work_keys_str_mv | AT roberthanthonyrojaschavez mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT mohammadfili mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT changzehan mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT syedarahman mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT isaiahglbicar mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT sullivangregory mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT annikahelverson mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT guipinghu mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT benjaminwdarbro mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT jishnudas mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT grantdbrown mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics AT hillelhaim mappingtheevolutionaryspaceofsarscov2variantstoanticipateemergenceofsubvariantsresistanttocovid19therapeutics |