Researchers at the Indian Institute of Technology (IIT) in Delhi have discovered the processes behind the development of SARS-CoV-2 in humans, which will aid in the study of COVID-19 pathophysiology, immune evasion, and the formation of dangerous variants. According to the seven-member study team, CpG (cytosine followed by guanine) levels in viral genomes have been linked to host-switching, virus replication efficiency, immune evasion, and a virus’s potential to cause illness.
The researchers discovered that within the first few months of human evolution, the rate of CpG depletion from SARS-CoV-2 genomes quickly declines. The study was published in the journal Molecular Biology and Evolution under the title ‘The Slowing Rate of CpG Depletion in SARS-CoV-2 Genomes is Consistent with Adaptations to the Human Host’.
‘ZAP is a host protein that binds to CpG-rich areas in SARS-CoV-2, the causal agent of the COVID-19 pandemic, and recruits other host proteins to break down the viral RNA. Several viruses, such as HIV-1, Influenza A virus, and SARS-CoV-2, prefer to lower their CpG content (by deleting CpGs) to minimize the host immune response, allowing for better viral reproduction and survival’, IIT Delhi’s Kusuma School of Biological Sciences’ Vivekanandan Perumal told PTI.
Over 1.4 million full-length SARS-CoV-2 sequences from throughout the world were analyzed by the researchers. They discovered that within the first few months of evolution in humans, the rate of CpG depletion from SARS-CoV-2 genomes rapidly declines. Furthermore, the CpG content of most SARS-CoV-2 variants of concern was lower. This study demonstrates the presence of selection factors other than ZAP that may result in CpG depletion in SARS-CoV-2 genomes,’ he noted.
SARS-CoV-2 has a uracil-rich genome (uracil is one of the four building blocks of RNA). The researchers discovered how uracils around CpGs lead to the rapid elimination of CpGs from SARS-CoV-2 genomes. ‘ Our findings establish the framework for future research into the complexities of virus-host interactions resulting in CpG depletion,’ stated IIT Delhi professor Manoj Menon. ‘ We found that the amount of CpG depletion in SARS-CoV-2 genomes was low over the first 17 months of the epidemic, equivalent to nearly 170 million recorded human infections,’ he stated.
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