tetano
Editor, Senior Moderator
Elife
. 2024 Dec 24:13:RP99833.
doi: 10.7554/eLife.99833. Accurate predictions of SARS-CoV-2 infectivity from comprehensive analysis
Jongkeun Park[SUP] #[/SUP][SUP] 1 [/SUP], WonJong Choi[SUP] #[/SUP][SUP] 1 [/SUP], Do Young Seong[SUP] #[/SUP][SUP] 1 [/SUP], Seungpil Jeong[SUP] 1 [/SUP], Ju Young Lee[SUP] 1 [/SUP], Hyo Jeong Park[SUP] 1 [/SUP], Dae Sun Chung[SUP] 1 [/SUP], Kijong Yi[SUP] 2 [/SUP], Uijin Kim[SUP] 3 [/SUP], Ga-Yeon Yoon[SUP] 3 [/SUP], Hyeran Kim[SUP] 4 5 [/SUP], Taehoon Kim[SUP] 4 5 [/SUP], Sooyeon Ko[SUP] 6 [/SUP], Eun Jeong Min[SUP] 7 [/SUP], Hyun-Soo Cho[SUP] 3 [/SUP], Nam-Hyeok Cho[SUP] 4 5 8 [/SUP], Dongwan Hong[SUP] 1 9 10 11 12 [/SUP]
Affiliations
An unprecedented amount of SARS-CoV-2 data has been accumulated compared with previous infectious diseases, enabling insights into its evolutionary process and more thorough analyses. This study investigates SARS-CoV-2 features as it evolved to evaluate its infectivity. We examined viral sequences and identified the polarity of amino acids in the receptor binding motif (RBM) region. We detected an increased frequency of amino acid substitutions to lysine (K) and arginine (R) in variants of concern (VOCs). As the virus evolved to Omicron, commonly occurring mutations became fixed components of the new viral sequence. Furthermore, at specific positions of VOCs, only one type of amino acid substitution and a notable absence of mutations at D467 were detected. We found that the binding affinity of SARS-CoV-2 lineages to the ACE2 receptor was impacted by amino acid substitutions. Based on our discoveries, we developed APESS, an evaluation model evaluating infectivity from biochemical and mutational properties. In silico evaluation using real-world sequences and in vitro viral entry assays validated the accuracy of APESS and our discoveries. Using Machine Learning, we predicted mutations that had the potential to become more prominent. We created AIVE, a web-based system, accessible at https://ai-ve.org to provide infectivity measurements of mutations entered by users. Ultimately, we established a clear link between specific viral properties and increased infectivity, enhancing our understanding of SARS-CoV-2 and enabling more accurate predictions of the virus.
Keywords: SARS-CoV-2; genetics; genomics; infectivity; protein prediction; viruses.
. 2024 Dec 24:13:RP99833.
doi: 10.7554/eLife.99833. Accurate predictions of SARS-CoV-2 infectivity from comprehensive analysis
Jongkeun Park[SUP] #[/SUP][SUP] 1 [/SUP], WonJong Choi[SUP] #[/SUP][SUP] 1 [/SUP], Do Young Seong[SUP] #[/SUP][SUP] 1 [/SUP], Seungpil Jeong[SUP] 1 [/SUP], Ju Young Lee[SUP] 1 [/SUP], Hyo Jeong Park[SUP] 1 [/SUP], Dae Sun Chung[SUP] 1 [/SUP], Kijong Yi[SUP] 2 [/SUP], Uijin Kim[SUP] 3 [/SUP], Ga-Yeon Yoon[SUP] 3 [/SUP], Hyeran Kim[SUP] 4 5 [/SUP], Taehoon Kim[SUP] 4 5 [/SUP], Sooyeon Ko[SUP] 6 [/SUP], Eun Jeong Min[SUP] 7 [/SUP], Hyun-Soo Cho[SUP] 3 [/SUP], Nam-Hyeok Cho[SUP] 4 5 8 [/SUP], Dongwan Hong[SUP] 1 9 10 11 12 [/SUP]
Affiliations
- PMID: 39717902
- PMCID: PMC11668528
- DOI: 10.7554/eLife.99833
An unprecedented amount of SARS-CoV-2 data has been accumulated compared with previous infectious diseases, enabling insights into its evolutionary process and more thorough analyses. This study investigates SARS-CoV-2 features as it evolved to evaluate its infectivity. We examined viral sequences and identified the polarity of amino acids in the receptor binding motif (RBM) region. We detected an increased frequency of amino acid substitutions to lysine (K) and arginine (R) in variants of concern (VOCs). As the virus evolved to Omicron, commonly occurring mutations became fixed components of the new viral sequence. Furthermore, at specific positions of VOCs, only one type of amino acid substitution and a notable absence of mutations at D467 were detected. We found that the binding affinity of SARS-CoV-2 lineages to the ACE2 receptor was impacted by amino acid substitutions. Based on our discoveries, we developed APESS, an evaluation model evaluating infectivity from biochemical and mutational properties. In silico evaluation using real-world sequences and in vitro viral entry assays validated the accuracy of APESS and our discoveries. Using Machine Learning, we predicted mutations that had the potential to become more prominent. We created AIVE, a web-based system, accessible at https://ai-ve.org to provide infectivity measurements of mutations entered by users. Ultimately, we established a clear link between specific viral properties and increased infectivity, enhancing our understanding of SARS-CoV-2 and enabling more accurate predictions of the virus.
Keywords: SARS-CoV-2; genetics; genomics; infectivity; protein prediction; viruses.