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Compiled a detailed map of the genome of the new coronavirus

Compiled a detailed map of the genome of the new coronavirus

Korean microbiologists compiled the first gene map of the new coronavirus. It turned out that the SARS-CoV-2 genome contains many so-called subgenomic RNAs whose functions are not fully understood. But many scientists managed to find out. The results of the study are published in the journal Cell.
Coronavirus SARS-CoV-2 belongs to the group of RNA viruses, the rather complex genome of which is encrypted in a very long molecule of ribonucleic acid (RNA). Penetrating into host cells, the virus replicates genomic RNA and creates many smaller ones called subgenomic RNAs. These subgenomic RNAs are used for the synthesis of various proteins from which the elements of new viral particles are built: spikes, membranes, membranes. Thus, if scientists find a way to suppress subgenomic RNA, then this will disrupt the life cycle of the virus in the body. But first you need to understand what each of these mysterious chains is responsible for.
Biologists from the RNA Research Center of the Institute of Basic Sciences of South Korea (IBS) under the guidance of professors Kim V. Narry and Chang Hyeshik in collaboration with the Korean National Institute of Health (KNIH) were able to analyze in detail the architecture of the SARS-CoV RNA genome -2 and draw up his gene map with a high degree of detail.
The researchers experimentally confirmed the presence of nine out of ten previously known subgenomic RNAs (included in the structure of viral particles and translated into specific viral proteins) in the coronavirus genome, and also found dozens of unknowns formed at different stages of the virus’s life cycle as a result of fusion and decomposition. In addition, they found out exactly where these genes are located on genomic RNA.
“This is not just a detailed structure of SARS-CoV-2,” said Professor Kim Narry in an IBS press release. “We have discovered numerous new RNAs and numerous unknown chemical modifications of viral RNAs.”

Life cycle of SARS-CoV-2 coronavirus. When the coronavirus spike protein binds to the receptor of the host cell, the virus enters the cell and then the membrane exfoliates, allowing genomic RNA to be present in the cytoplasm. RNA ORF1a and ORF1b are created by genomic RNA and then translated into pp1a and pp1ab proteins, respectively. Proteins pp1a and ppa1b are cleaved by a protease to form 16 non-structural proteins. Some non-structural proteins form the RdRp replication / transcription complex (RNA-dependent RNA polymerase), which use genomic positive chain RNA as a template. Genomic positive RNA produced during replication becomes the gene for a new viral particle. Transgenic subgenomic RNAs are translated into structural proteins: spike protein S, membrane E protein, membrane M protein, and N nucleocapsid protein, which form a viral particle. The proteins of the thorn, membrane and membrane enter the endoplasmic reticulum, and the nucleocapsid protein combines with the strand of genomic positive RNA, turning into a nucleoprotein complex. They merge into a complete viral particle in the compartment of the endoplasmic reticulum – the Golgi apparatus and are excreted into the extracellular region through the Golgi apparatus and the vesicle.

The authors suggest that RNAs modified during the life cycle can obtain new properties that distinguish them from unmodified ones, even if they carry the same genetic information. According to researchers, the identification of unknown characteristics of RNA will allow you to find the key to fight the new coronavirus.
“Although further study is required, it can already be said that such molecular events can lead to a relatively rapid evolution of coronavirus. Moreover, we find many unknown chemical modifications of viral RNAs. It is not yet clear what these modifications do, but it is possible that they help the virus avoid attacks from the host cell, “says Kim.
The success of Korean microbiologists is based on the application of two additional methods: sequencing of circular DNA molecules (nanoboles) and direct nanopore RNA sequencing.
Conventional sequencing methods require a step-by-step process of cutting and converting RNA into DNA before reading it. Nanopore sequencing allows direct analysis of all long viral RNA without fragmentation, and sequencing of circular DNA molecules has the advantage of analyzing a large number of sequences with high accuracy. These two complementary methods have proven to be very effective for viral RNA analysis.
“Now we’ve got a high resolution gene map of the new coronavirus that will help us find every bit of the genes on all SARS-CoV-2 RNAs and all RNA modifications. It’s time to investigate the functions of the newly discovered genes and the mechanism underlying the fusion of viral genes. We we’ll also need to work on RNA modifications to see what role they play in virus replication and the immune response. We strongly believe that our research will contribute to the progress of diagnosis and therapy to more effectively fight the virus, “says Kim.

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