by
…Back in 2007, even before the Wuhan P4 had been built, researchers at the Wuhan Institute of Virology published a paper in the Journal of Virology. More details can be read in a paper authored by a group of anonymous researchers, but I’ll abstract the key points of the 2007 Wuhan Institute here:
- “First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor.” (Translation: “We found a SARS-like virus that couldn’t infect human cells.”)
- “We investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat.” (Translation: “We combined the SARS-like virus with HIV genes in a specific attempt to make it infectious to humans.”)
- “Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2” (Translation: “Thanks to our engineering, the new virus (“chimeric S”) can infect human cells.”)
Eight years later another paper came out of the newly functional Wuhan P4 lab. Here’s a portion of the abstract:
“Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.” (Translation: We found another SARS-like virus in bats and created a chimera that could infect humans and replicate A LOT in the human lung, and we also found that the current SARS vaccines and treatments didn’t work against it. And that point we decided to create an entirely synthetic version of this new virus.)
Right here is the possible COVID-19 progenitor. In fact, this was THE paper that caused the controversy to be aired in Nature.
In late November of 2019, the P4 group published another key paper. Here’s a portion of the abstract:
“Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays.” (Translation: We found out how antibodies that your immune system generates create a Trojan horse for the virus to get into your cells.)
And these gems from the Discussion:
“Moreover, a SARS-CoV RBD-specific neutralizing MAb mediates ADE of SARS-CoV pseudovirus entry. These results demonstrated that ADE of coronaviruses is mediated by neutralizing MAbs that target the RBD of coronavirus spikes. In addition, the same coronavirus strains that led to the production of fully neutralizing MAbs can be mediated to go through ADE by these neutralizing MAbs.” (Translation: We proved to our satisfaction the mechanism by which the antibodies generated by your own immune system actually create a Trojan horse for the virus to hide in, so we’re done with our research!) …
recently published by two South Korean researchers:
“The research team analyzed all ribonucleic acid (RNA) transcripts produced by the SARS-CoV-2 in host cells by using next-generation sequencing, nanopore and nano ball sequencing. The exact location of the viral gene was found in the study while confirming the RNAs that were not found with existing methods. The team also confirmed at least 41 chemical mutations were made to the viral RNA. By finding the location, the research team identified how the viral transcripts were constructed, and they could pinpoint where the viral genes were located in the genome. According to the research, SARS-CoV-2 is in RNA form, and the virus infiltrates into the host cell and replicates while producing various subgenomic RNAs based on the genomic RNA. This subgenome synthesizes several proteins, such as spikes and shells, which make up the structure, and form a virus in the host cell with the cloned gene. After the replication is done, the virus exits the cell and infects other cells. The sum of RNA produced in the host cell is known as the Transcriptome. Previously, 10 subgenomic RNAs were known to exist, but the team’s study unboxed that only nine sub-genome RNAs actually existed. Besides, the research team discovered dozens of more RNAs produced in the hosting cell. Chemical modifications such as methylation in viral RNA were observed as well. Various biochemical changes that occur at the RNA level after transcription is called epitranscriptomes, just as those happening at the DNA-level such as DNA methylation are known as epigenomes.” (Translation: By doing a much more detailed analysis of the genome we’ve actually mapped these large numbers of mutations to the actual part of the genome that translates for specific viral proteins. And this is a virus that LOVES to mutate.)
“It is necessary to check whether the newly discovered RNAs behave as proteins that regulate viral replication and the host’s immune response,” Director Kim said. “The chemical modification of RNA seems to have relations with virus survival and immune responses.” Their general approach has also been confirmed by other Chinese researchers. (Translation: It really doesn’t matter what “strain” you were infected with; the course of the disease will depend on what mutations occur and how those mutations affect the production of sgRNAs. And there are LOT of mutations.)
https://carolinefifemd.com/2020/04/24/covid-19-the-origins-story-by-guest-blogger-marissa-carter-phd/
…………….................................................................................….
Jie Cui
Principal Investigator,
Wuhan Institute of Virology, Chinese Academy of Sciences, China
Interest: Taking emerging infectious viruses and endogenous viruses as example, Dr Cui’s research areas include virus evolution, model construction for the interaction of virus and host cells, and the influences of endogenous virus to host genome
Peng Gong
Principle Investigator,
Wuhan Institute of Virology, Chinese Academy of Sciences, China
Interest: Dr Gong’s lab is focused on the crystal structure research of RNA virus polymerases, especially its catalytic mechanism and modulation to virus replication.
Qinxue Hu
Principle Investigator,
Wuhan Institute of Virology, Chinese Academy of Sciences, China
Interest: Dr. Hu’s lab is focused on HIV research, especially for 1)HIV-1 mucosal infection and immunity; 2) HSV-2/HIV-1 co-infection and inhibition; 3) Early infection and intervention of mucosally transmitted viruses
Jian-Hua Wang
Principal Investigator,
Institute Pasteur of Shanghai, Chinese Academy of Sciences
Interest: Dr. Wang’s research interests focus on the interactions of HIV-1-host cells and viral pathogenesis, and three aims are included: 1) HIV-1 mucosal infections and host cell-mediated viral dissemination; 2) The contribution of dendritic cells immunal activation to viral pathogenesis during co-infections of HIV-1 with other pathogens; 3) To explore the host factors that could restrict HIV-1 replication in monocytic cells.
Xi Zhou
Principal Investigator,
Wuhan Institute of Virology, Chinese Academy of Sciences, China
Interest: 1) RNAi-mediated innate antiviral immunity and viral evasion of RNAi; 2) Viral RNA replication; 3) RNA remodeling proteins for viral life cycle; 4) Surface display
No comments:
Post a Comment