The rapid spread of acute respiratory coronavirus 2 (SARS-CoV-2) syndrome has captured more than 111 million people worldwide and has led to COVID-19 pandemic. Many pangolin and bat viruses are closely linked to SARS-CoV-2, which appears to have its zoonotic origin.
Researchers have found a 96% similarity in nucleotide sequence between coronavirus bat (RaTG13), isolated from
s in China in 2013, and SARS-CoV-2 and 9797% similar to amino acid with the protein Spike (S). This S protein performs two essential functions, i.e., mediating receptor-binding and membrane fusion. Thus, spike proteins are viewed as a major determinant of coronavirus on host tropism.
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Similarly, a high percentage of appearance was detected in viruses that were present Manis javanica (pangolins). A 97.4% amino acid concentrate has been reported to be present in the receptor binding domain (RBD) of the spike protein found in the pangolin virus.
The study of several pandemics over two decades, ie, the manifestation of swine diarrhea coronrheirus syndrome (SADS-CoV), acute respiratory coronavirus syndrome (SARS-CoV), and Middle Eastern respiratory coronavirus (MERS-CoV) has shown the -saoghal comas epidem coronaviruses.
Scientists have explained that a small change in the genetic sequence of the virus could play an important role in converting it to a new host. Mutation in just two amino acids established an essential mutation in the SARS-CoV and MERS-CoV spike proteins needed to convert to humans.
Fig 1. Selective wipe analysis. (a) Selective deletion regions (shown as red blocks) identified in 182,792 SARSSARS-CoVCoV-2 genomes, using OmegaPlus (blue lines) and RAiSD (yellow lines). The common outliers (0.05 cutoff, purple dots) from both methods were used to define selective cutoff sections. (b) Nonspecific difference (Thr372Ala) between SARS-CoVCoV-2 SARS and four other Sarbecovirus components found in the putative selective clearance category (22,529 22,529-22,862).
A similar change was also found in many other viruses, such as Ebola, where alanine-to-valine mutation at position 82 in the glycoprotein initiated the human mutation, which triggered the revolution. Many recent events associated with RNA virus, for example, West Nile virus, Zika virus, and Chikungunya virus, have occurred as a result of a single amino acid mutation in the nucleotide sequence of the virus.
In the case of SARS-CoV-2, a single mutation at position 614 in the S protein induced a change in the production of single aspartic acid to glycine, which has led to an increase in reproductive vigor in humans. However, it was not yet known which genetic markers of SARS-CoV-2 are responsible for the change of host from animal to human.
Scientists believe that a strong name of positive selection occurs when the virus of its host changes through rapid evolution or transgender transmission.
Such an event was reported for the brief SARS outbreak that occurred in 2002-2003. During this period, a series of mutations or mutations in identified SARS-CoV genomes occurred based on dN / dS assays.
These experiments are designed to compare eukaryotic hybrids. However, the limitation of these tests is that they cannot find a signature of positive selection in viral sequences with small sequence multiplication.
Recently, researchers have used highly advanced methods capable of detecting selective deletions. In this way, a favorable selective mutation spreads through the population, causing a decrease in the sequence variability rate at nearby genomic sites.
With the help of unprecedented statistical tools, scientists have analyzed more than 182,000 SARS-CoV-2 genomes and found that positive selection plays an important role in evolution variable SARS-CoV-2. Considering coronavirus host tropism, researchers provided strong evidence that the residue of spike protein 372 contributes to a mutated mutation, which itself accumulates the reproduction in human lung cells. The research by scientists in the US and Israel is posted online on the bioRxiv* preprint server.
The genetic mutation, i.e., threonine-to-alanine mutation, could allow the virus to reproduce more strongly within human cells. This also encourages effective person to person transmission.
Previous computational-based analysis and pseudotyped virus analysis have identified advanced selection in SARS-CoV-2.
Even though a study of the pseudoviruses provided much useful information, the complete life cycle of the virus or the interaction between different viral proteins and the host were not found. More recently, the use of live viruses has helped develop hamster models that replicate human-to-human transmission.
In summary, current research indicates that there is a specific footprint of progressive selection around nonlinear alteration (A1114G; T372A) within RBD of the SARS-CoV-2 spike protein. This plays a vital role in enabling species barriers and also achieving animal-to-human transmission.
Further, the structural analysis also reveals that the replacement of threonine with alanine in SARS-CoV-2 removes the glycosylation site at N370. Such changes reflect a favorable binding of the virus to the human cell receptor (ACE2).
Another interesting suggestion was that, contrary to previous assumptions, the Huanan seafood market, China, may not be the starting point of the SARS-CoV-2 novel. The unconscious transmission may have occurred elsewhere for a period of time that gave the ancestor virus sufficient time to adapt to human replication.
* Important message
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical / behavioral practice, or treated as fixed information.