Omicron could be ten times more contagious than the original SARS-COV-2 or about twice as infectious as the Delta variant, says new study published on preprint server.
Omicron (B.1.1.529), the latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, has sparked worldwide fear due to its infectious nature and vaccine escape mutations.
This variant carries an unusually high number of mutations, 32, on the spike (S) protein, the main antigenic target of antibodies generated by either infections or vaccination. In comparison, the devastating Delta variant has only 5 S protein mutations, which posed a high potential global risk and has spread internationally.
Therefore, the “panic button” has been pushed in several cases worldwide, and many countries have enacted travel restrictions to prevent the rapid spread of the Omicron variant.
However, doing a complete experimental assessment of Omicron could take weeks or even months.
In this study, scientists present a comprehensive quantitative analysis of Omicron’s infectivity, vaccine-breakthrough, and antibody resistance.
The study highlights that the mutations on the Omicron variant are widely distributed on multiple proteins of SARS-CoV-2 such as NSP3, NSP4, NSP5, NSP6, NSP12, NSP14, S protein, envelope protein, membrane protein, and nucleocapsid protein.
The focus is the mutations on the S protein receptor-binding domain (RBD) for the potential impact on infectivity and antibody resistance caused by this new variant. This is due to the fact that the RBD located on the S protein facilitates the binding between the S protein and the host angiotensin-converting enzyme 2 (ACE2). Such S-ACE2 binding helps the SARS-CoV-2 enter the host cell and initiates the viral infection process.
Several studies have shown that the binding free energy (BFE) between the S RBD and the ACE2 is proportional to the viral infectivity. As such, an antibody that binds strongly to the RBD would directly neutralize the virus. Indeed, many RBD binding antibodies are generated by the human immune response to infection or vaccination.
Monoclonal antibodies (mABs) targeting the S protein, particularly the RBD, are designed to treat viral infection. As a result, any mutation on the S protein RBD would cause immediate concerns about the efficacy of existing vaccines, mAbs and the potential of reinfection.
In the current work, the researchers used their own developed artificial intelligence (AI) model, dubbed the TopNetmAb with tens of thousands of experimental data points and extensively validated by experimental data on SARS-CoV-2.
Omicron has three mutations at the furin cleavage site and 15 mutations on the RBD, suggesting a significant change in its infectivity. Due to natural selection, the virus enhances its evolutionary advantages at the RBD either by mutations to strengthen the ACE2-RBD binding affinity or by mutations to escape antibody protection. Since the virus has optimized its Infectivity in human cells, one should not expect a dramatic increase in the viral infectivity by any single mutation. An effective infection pathway is for the virus to have multiple RBD mutations to accumulatively enhance its infectivity, which appears to be the case for Omicron.
In comparison, Omicron is about 2.8 times as infectious as the Delta.
Omicron’s Vaccine breakthrough
Vaccination has been proven to be the most effective means for COVID-19 prevention and control. There are four types of vaccines, i.e., virus vaccines, viral-vector vaccines, DNA/RNA vaccines, and protein-based vaccines. Essentially, the current COVID-19 vaccines in use mainly target to the S protein. The 32 amino acid changes, including three small deletions and one small insertion in the spike protein, suggest that Omicron may be induced by vaccination. As a result, these mutations may dramatically enhance the variant’s ability to evade current vaccines.
In general, it is essentially impossible to accurately characterize the full impact of Omicron’s S protein mutations on the current vaccines in the world’s populations. First, different types of vaccines may lead to different immune responses from the same individual. Additionally, different individuals characterized by race, gender, age, and underlying medical conditions may produce different sets of antibodies from the same vaccine. Moreover, the reliability of statistical analysis over populations may be limited because of the inability to fully control various experimental conditions.
Based on 132 three-dimensional (3D) structures of antibody-RBD complexes, they say that Omicron may be twice more likely to escape current vaccines than the Delta variant.
Omicron’s Antibody resistance
The assessment of Omicron’s mutational threats to FDA-approved mAbs and a few other mAbs in clinical development is of crucial importance.
Eli Lilly’s monoclonal antibodies (mAbs) that have been approved by the Food and Drug Administration (FDA) may be seriously compromised. Omicron may potentially impair the efficacy of Celltrion and Rockefeller University monoclonal antibodies. However, it appears to have a negligible effect on the Regeneron mAb combination.
The study concludes that Omicron may be over ten times more contagious than the original virus or about twice as infectious as the Delta variant.
Important Note: arXiv e-prints are not peer-reviewed; they should not be used without context to guide clinical practice or health-related behavior.
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