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Latest Research Paper finds Common Weakness of Coronavirus

 

COVID Research: Nearly 200 Scholars Jointly Find Common Weaknesses of Corona virus

The new coronavirus (SARS-CoV-2), SARS virus (SARS-CoV-1) and MERS virus (MERS-CoV), the three deadly coronaviruses, have common weaknesses, which may help scientists find the coronavirus The universal method. On October 15, local time, a paper published online by the top academic journal "Science" provided a glimmer of hope for mankind to deal with the coronavirus.

 

Research Paper titled: Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

It is worth mentioning that the paper was completed by nearly 200 researchers from 14 institutions in 6 countries including the United States, France, and Germany. The title of the paper is "Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms".

 

The paper pointed out that in the past 20 years, the world has encountered three fatal human respiratory syndromes related to coronavirus infection: 

severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012 And COVID-19 in 2019. 

These three diseases are caused by the zoonotic coronavirus SARS-CoV-1, MERS-CoV and SARS-CoV-2. Among them, the COVID-19 epidemic caused by SARS-CoV-2 is still spreading globally, and has caused more than 38 million confirmed cases and more than 1 million deaths.

 

200 scientists confirms the commonalities between coronaviruses

This latest study jointly completed by the above-mentioned nearly 200 scientists confirms the commonalities between coronaviruses and provides several common cellular processes and protein targets. 

They believe that these should be regarded as targets for current and future pandemic treatment interventions.

 

 

Study on the conservative target proteins and cellular processes of these coronaviruses

Based on the researchers’ previous work published in academic journals, the research team comprehensively studied SARS-CoV-2 and SARS-CoV-1 using biochemical, proteomics, genes, structure, bioinformatics, virology and imaging methods. And MERS-CoV, to identify the conservative target proteins and cellular processes of these coronaviruses.

 

Using the map of how the SARS-CoV-2 virus protein interacts with the target human host cell protein, the research team constructed the protein-protein interaction map of SARS-CoV-1 and MERS-CoV, highlighting the several common features of the three coronaviruses. Key cellular processes.

 

The research team believes that these common pathways and protein targets are high-priority targets for therapeutic intervention against this epidemic and future epidemics.

 

More importantly, the research team discovered that the mitochondrial outer membrane protein Tom70 interacts with the SARS-CoV-1 and SARS-CoV-2 proteins Orf9b. Tom70 is usually involved in the activation of mitochondrial antiviral signal protein (MAVS), which is essential for the innate immune response against viruses. 

Orf9b inhibits the interaction between Tom70 and heat shock protein (Hsp90) by binding to the substrate recognition site of Tom70, which plays a key role in the interferon pathway and inducing apoptosis after virus infection.

 

Latest Research Paper finds Common Weakness of Corona virus
Coronavirus Research Paper


Use of cryo-electron microscopy (cryoEM) in Coronavirus research

The research team also used cryo-electron microscopy (cryoEM) to characterize the interaction. They found a noteworthy phenomenon. Orfb9 normally forms a dimer, which is composed entirely of β-strand folds, and when combined with Tom70, it becomes an α-helix form, which indicates that the viral protein has a high degree of flexibility.

 

Using the structural image of the binding protein, the research team also found that a key residue that interacts with Hsp90 has changed, indicating that Orf9b may regulate key aspects of immune response, interferon and apoptosis signals through Tom70.

 They pointed out that the functional significance and regulation of the Orf9b-Tom70 interaction needs further experimental explanation. However, this conservative interaction between SARS-CoV-1 and SARS-CoV-2 may have value as a pan-coronavirus therapeutic target.

 

Under the guidance of the three coronavirus interaction groups, the research team performed CRISPR and RNA interference (RNAi) knockouts on the putative host proteins of each virus, and studied how the lack of these proteins can change the ability of SARS-CoV-2 to infect human cells .

 

They determined that 73 proteins are important for virus replication and used this list to prioritize drug candidates. These include the IL-17 receptor, an inflammatory signaling molecule, which has been identified as an important indicator of the severity of new coronary pneumonia in many previous studies Prostaglandin E2 synthase (PGES-2), which is related to the Nsp7 protein in the three viruses Functional interaction, and the non-opioid receptor sigma-1, which can interact with the Nsp6 of SARS-CoV-1 and SARS-CoV-2. 

The research team has also demonstrated through experiments that this is a promising drug target point.

 

Retrospective analysis of the treatment on COVID-19 Patients

On the basis of the above research and data, the research team conducted a retrospective analysis of the treatment of approximately 740,000 new COVID patients.

 

They found that among outpatients, patients who newly used indomethacin, a non-steroidal anti-inflammatory drug (NSAID) that targets PGES-2, were better than those who used non-steroidal drugs that did not target PGES-2.

Patients with the anti-inflammatory drug celecoxib (celecoxib) are less likely to require hospitalization or hospitalization.

 

In hospitalized patients, the research team compared the effectiveness of typical antipsychotic drugs and atypical antipsychotic drugs. The former has activity on the receptor sigma-1, while the latter does not.

 Compared with new users of atypical antipsychotics, half of new users of typical antipsychotics have developed to the level of mechanical ventilation. They pointed out that typical antipsychotic drugs may have significant side effects, but there are other drugs that target sigma-1, and more drugs are still in development.

 

"These analyses show that biological and molecular information can actually be transformed into treatments for COVID-19 and other viral diseases." European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) team leader, paper newsletter Professor Pedro Beltrao, one of the authors, said, “After more than a century after the emergence of relatively harmless coronaviruses, we have encountered three deadly coronaviruses in the past 20 years. 

Through cross-species research, we have the ability to predict Broad-spectrum coronavirus therapy that may be effective in treating the current epidemic. We believe this will also provide promising treatments for future coronaviruses."




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