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Prediction method of mutation site of virus adaptive to human host, and application thereof

A mutation site, virus technology, applied in the fields of viral genetics and cell biology

Pending Publication Date: 2020-09-15
BEIJING INST OF GENOMICS CHINESE ACAD OF SCI CHINA NAT CENT FOR BIOINFORMATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, much remains unknown about the mechanisms by which coronaviruses migrate between different hosts and what adaptive mutations in their genomes lead to their adaptation to spread in humans.

Method used

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  • Prediction method of mutation site of virus adaptive to human host, and application thereof
  • Prediction method of mutation site of virus adaptive to human host, and application thereof
  • Prediction method of mutation site of virus adaptive to human host, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1 Screening of coronaviruses losing targets attacked by host miRNAs during host conversion

[0070] The genome sequences of 7 coronaviruses capable of infecting humans, including coronavirus strains with human hosts and closely related evolutionary strains with bats or other non-human animals as hosts, were used as the research objects. First, compare the human miRNA sequence database (such as miRBase, http: / / mirbase.org / ) and tissue expression database (such as SEAweb, http: / / sea.ims.bio / ), and search for the expression in the above-mentioned virus genome and human lung tissue. The complementary target sequence of miRNA, using the conventional miRanda algorithm tool (http: / / www.microrna.org), can find hundreds of targets on each viral genome, and the cumulative miRNA abundance can reach more than 95%, so miRanda Algorithms used to estimate miRNA target sequences for viruses were apparently too lenient and produced many false positive targets. Based on the miRa...

Embodiment 2

[0074] Example 2 Adaptive mutation of SARS-CoV-2 spreading in humans

[0075] By comparing the RNAi-sensitive targets in the Wuhan-Hu-1 strain (the reference genome of SARS-CoV-2) and its closest bat host strain RaTG13, it was found that the two strains shared 12 common targets, but both Targets of low-abundance CoVT miRNAs in human lung tissue. However, the two targets with the highest abundance in human lung tissue miRNAs that can attack the RaTG13 genome are not in the Wuhan-Hu-1 strain genome. These two sites are: site 1 is miR-146b-5p (abundant 2.95%), and site 2 is the target of miR-200c-3p (0.27% abundance). Deletion of these two sites in the SARS-CoV-2 viral genome reduced the abundance of human lung CoVT-miRNA from 3.65% against the RaTG13 strain to 0.68% against the Wuhan-Hu-1 strain, thus allowing it to escape RNAi challenge triggered by two highly abundant human lung CoVT-miRNAs. Carefully comparing these two targets in the RaTG13 strain with the corresponding p...

Embodiment 3

[0077] Example 3 Adaptive mutation of SARS coronavirus spreading in human host

[0078] By comparing RNAi sensitive targets on the genomes of SARS-related strains, including Tor2 (human host), SZ3 (civet host) and Rs4231 (bat host), Figure 5 It was shown that the bat host SARS strain has the attack target of human lung miR-99b-5p (abundance 1.25%), but this site is in the genome of the human host and the civet host strain, which is identical to 5 of miR-99b-5p. The complementary U of the 11th A base at the ' end undergoes U→C conversion, which destroys its hybridization with miRNA, resulting in the loss of the RNAi sensitive site.

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Abstract

The invention discloses a prediction method of a mutation site of virus adaptive to a human host, and application thereof, and in particular relates to adaptive mutation of virus adaptive to a human host, and application thereof as a drug target and a biomarker. The fact that animal host coronavirus exists in a target attacked by human lung tissue miRNA is found for the first time in the invention; human coronavirus loses targets on these genome through the adaptive mutation so as to get the capability of spreading in the human host; the site of the coronavirus adaptive mutation provided by the invention can be used as a drug design target for treating or preventing coronavirus infection, and a biomarker for checking the coronavirus host range; simultaneously, the algorithm for predictingthe target attacked by the host miRNA on the virus genome provided by the invention can be used for predicting RNAi sensitive targets of all kinds of virus; and the drug design target for treating andpreventing corresponding virus infection and the host range checking biomarker are developed.

Description

technical field [0001] The invention relates to the fields of viral genetics and cell biology, in particular to a method for predicting mutation sites of viruses adapting to human hosts and its application. Background technique [0002] SARS-CoV-2 (or hCov-19) is the causative virus of COVID-19. SARS-CoV-2 is the seventh known human-hosted virus in the genus Coronavirus. The other six diseases include SARS and MERS, which cause severe acute respiratory syndrome, and four (OC43, 229E, NL-63, and HKU-1) viruses that often cause mild respiratory infections with common cold-like symptoms. In addition to humans, the hosts of coronaviruses include a variety of mammals, and most human coronaviruses are thought to have originated from bat-hosted strains. However, there are still many unknowns about the mechanism of coronavirus migration between different hosts and what adaptive mutations in its genome lead to its adaptation to spread in the human population. [0003] As a positiv...

Claims

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Application Information

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IPC IPC(8): C12Q1/70C12N15/11G16B30/10G16B20/50A61K45/00A61K31/7088A61P31/14
CPCC12Q1/701G16B30/10G16B20/50A61K45/00A61K31/7088A61P31/14C12Q2600/156
Inventor 康禹于军孟庆仁楚亚男陈婧邵长君
Owner BEIJING INST OF GENOMICS CHINESE ACAD OF SCI CHINA NAT CENT FOR BIOINFORMATION
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