The SARS-CoV2 virus has been the major focus of scientific research as well as the predominant news story since early 2020. One of the biggest concerns with the SARS-CoV2 virus is the emergence of new and more potent variant strains due to mutations in the viral genome. When the virus infects and replicates in host cells, new mutations appear in the genome. Most of the mutations do not have functional consequences such as increased infectivity or immune evasion. However, there are some mutations that improve viral infectivity or disease spread resulting in the development of new variant strains. The SARS-CoV2 genome is a single strand of positive sense RNA that encodes genes required to build new viral particles. The primary proteins of interest encoded by the viral genome are the spike, envelope and membrane proteins as well as 2 replicase polyproteins1. Mutations in the spike protein are of high interest as the spike protein binds to the host ACE2 protein (angiotensin converting enzyme 2) prior to entering the cell. Once the virus is in the host cell, it hijacks the translational machinery to replicate and then new viral particles are released to repeat the infection-replication-release cycle.
Currently, there are 4 strains that are considered “variants of concern” in the US2– the alpha, beta, gamma and delta variants. The delta variant is currently the most common variant in the US and is of significant concern as it is highly contagious and can be spread by vaccinated individuals. Additionally, the available vaccines may not be sufficiently efficacious against the delta variant3. The amino acid changes in each variant have been identified and published4 and interestingly several changes are convergent where the same change arises independently in multiple variant lineages. One example is the N501Y mutation that has been identified in the alpha, beta and gamma variants. Conversely, variant specific mutations that have functional consequences have been identified – a couple of examples are the L452R and E484Q mutations in the delta variant that have been show to affect recognition by antibodies4.
The scientific community is currently focused on characterizing emerging variants especially the strains that are more contagious or cause more severe disease. Some of the new variants of interest that have been identified in the past few months include the eta, iota, kappa and lambda strains. The lambda strain has been of particular interest due to 2 amino acid changes (T76I and L452Q) that increase infectivity and a unique 7 amino acid deleted in the N-terminal of the spike protein that helps evade neutralizing antibodies5. Along with the characterization of emerging variants, there is a great deal of interest in developing reliable methods to predict future variants. One approach is to analyze genomic surveillance datasets where the viral genome sequences are compared over time to identify changes and high frequency mutations across multiple regions and multiple countries, based on a recent report6. This study used a complex combination of biological and epidemiological parameters to build a forecasting model to predict mutations in the SARS-CoV2 spike protein6. The most forecasted mutations have shown increase in frequency globally and this data is useful for ongoing analysis of whether the available vaccines can trigger the formation of neutralizing antibodies against the new variants. One school of thought is that the new variants will be derived from the contagious delta variant, which has been able to evade the immune system but this hypothesis will need to be validated in more detail using forecasting models and epidemiological data.
Given the rapid rate of mutation of the SARS-CoV2 virus and emergence of new strains, it is clear that the scientific community has to continue to refine forecasting models based on real-world data, and work collaboratively to stay ahead of the ever-changing SARS-CoV2 virus and manage the global pandemic.
Leave a Reply