Evolution of SARS-CoV-2 spike gene for human adaptation

The rapid spread of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has infected more than 111 million people worldwide, resulting in a COVID-19 pandemic. Many scale and bat-derived viruses are closely associated with SARS-CoV-2, suggesting that they are likely to be the origin of zoonotic diseases.

Researchers have found a 96% similarity in nucleotide sequence between bat coronaviruses (RaTG13).

s occurred in China in 2013 and has an amino acid similarity of about 97% with SARS-CoV-2 and spike (S) proteins. This S protein plays two important roles in mediating receptor binding and membrane fusion. Therefore, peplomer is considered an important host-oriented coronavirus determinant.

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Similarly, the percentage of similarities is sweet javanica (Pangolins). A 97.4% amino acid match has been reported to be present in the receptor binding domain (RBD) of the peplomer found in pangoline virus.

Decades of epidemic research: pig acute diarrhea syndrome coronavirus (SADS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) Showed the world the possibility of an emergence epidemic Coronavirus..

Scientists explain that small changes in the gene sequence of the virus can play an important role in adapting to new hosts.Minor changes in just two amino acids established the necessary changes in SARS-CoV and MERS-CoV. Spike protein Needed to adapt to humans.

Figure 1. Selective sweep analysis. (A) Selective sweep regions identified in 182,792 SARSSARS-CoVCoV-2 genomes (shown as red blocks) using OmegaPlus (blue line) and RAiSD (yellow line). We have defined selective sweep areas using common outliers from the two methods (0.05 cutoff, purple dots). (B) Non-synonymous differences between SARS SARS-CoVCoV-2 and the other four salvecovirus members found in the presumed selective sweep area (22,529 22,529-22,862) (Thr372Ala).

Similar changes were seen in many other viruses, such as Ebola, where a single alanine-to-valine mutation at position 82 of the glycoprotein initiated adaptation to humans, which caused its development. Many recent outbreaks associated with RNA viruses such as West Nile virus, Zika virus, and Chikungunya virus have also been caused by changes in a single amino acid in the nucleotide sequence of the virus.

In the case of SARS-CoV-2, a single mutation at position 614 of the S protein caused a single production change. Aspartic acid To glycine, it brought about an increase in human replication vitality. However, the genetic determinants of SARS-CoV-2 involved in the host animal-to-human transition remained unknown.

Scientists believe that when the virus changes hosts due to rapid evolution or interspecific transmission, there are strong signs of positive selection.

Such incidences were reported in a brief epidemic of SARS that occurred between 2002 and 2003. During this period, a series of adaptive changes or mutations occurred in the SARS-CoV genome characterized based on the dN / dS test.

These tests are designed to compare eukaryotic species. However, the limitation of these tests is that they cannot detect the characteristic signature of positive selection in viral strains with small sequence differences.

Recently, researchers have used advanced methods that can detect selective sweeps. This method selectively spreads the preferred mutations throughout the population and reduces the level of sequence variability at nearby genomic sites.

With the help of unprecedented statistical tools, scientists analyzed more than 182,000 SARS-CoV-2 genomes and found that positive selection plays an important role in the adaptive evolution of SARS-CoV-2. Given the host orientation of the coronavirus, researchers provided strong evidence that peplomer residue 372 contributed to adaptive mutations, which in turn aggregated their replication in human lung cells. .. Studies by US and Israeli scientists are posted online. bioRxiv* Preprint server.

Genetic modification, the change from threonine to alanine, may allow the virus to replicate more actively in human cells. It also promotes efficient person-to-person transmission.

Previous calculation-based studies and pseudovirus studies have identified a positive selection of SARS-CoV-2.

Pseudovirus studies have provided a vast amount of useful information, but have not yielded an entire viral life cycle or interactions between different viral proteins and hosts. Recently, the use of live viruses has helped develop hamster models that reproduce human-to-human transmission.

In summary, current studies show the presence of a clear footprint of positive selections around non-synonymous changes (A1114G; T372A) within the RBD of SARS-CoV-2 pedplomers. It plays an important role in neutralizing species barriers and achieving interspecific transmission from animals to humans.

In addition, structural analysis has shown that changes in threonine and alanine in SARS-CoV-2 eliminate the glycosylation site of N370. These changes indicate that the virus binds well to human cell receptors (ACE2).

Another interesting proposal was that, unlike previous assumptions, China’s South China seafood market may not be the starting point for the new SARS-CoV-2. The transmission may have occurred unnoticed elsewhere for a period of time that the ancestral virus provided sufficient time to adapt to human replication.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.