Comparative analysis reveals common vulnerabilities in coronavirus

Three fatal human respiratory syndromes associated with coronavirus (CoV) infection have emerged over the last two decades. They are Severe Acute Respiratory Syndrome (SARS) in 2002, Middle East Respiratory Syndrome (MERS) in 2012, and Coronavirus Disease 2019 (COVID-19) in 2019.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is closely associated with SARS-CoV-1 and MERS. Coronavirus, More deadly than SARS-CoV-2, but less infectious.

MERS Corona Virus Particles Colored scanning electron micrographs of MERS virus particles (yellow) sprouting and adhering to the surface of infected VEROE6 cells (blue). Color-enhanced image taken at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Credit: NIAID

The ongoing COVID-19 pandemic has affected more than 39.8 million lives worldwide and has killed more than 1.11 million to date. The pandemic has caused devastating socio-economic consequences in many countries around the world. Symptoms of COVID-19 vary widely based on several factors and can lead to long-term serious illness in some patients. Some studies suggest that symptoms may persist after recovery and negative real-time polymerase chain reaction (RT-PCR) test results.

This unprecedented challenge posed by COVID-19 is extensive for developing vaccines and reused antiviral therapies that can provide potential treatment with a known safety profile and a shorter timeline of development. Encouraged a great effort. The diversion of remdesivir, antiviral nucleoside analogs, and the anti-inflammatory steroid dexamethasone gave hope that existing compounds could be crucial in the fight against the COVID-19 pandemic. Nonetheless, there is no approved treatment for COVID-19 yet, and efforts to find vaccines or drugs are the evolution of SARS-CoV-2 and potential drug resistance that may be achieved during evolution. Can be complicated by.

A new coronavirus SARS-CoV-2 color scanning electron micrograph of apoptotic cells (pink) strongly infected with SARS-COV-2 virus particles (green) isolated from a patient sample. Image taken at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Comparison of three coronavirus viruses and human protein interactions

A large team of researchers from various universities and laboratories in the United States and Europe conducted a comparative analysis of viral-human protein interactions and the localization of viral proteins in all three viruses. Their work is published in Science Magazine, the prestigious academic journal of the American Society for advancing science.

Researchers performed functional genetic screening to identify host factors that functionally interfere with the growth of coronavirus. These factors included the mitochondrial chaperone protein Tom70, which interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b. This interaction was structurally characterized with the help of cryo-electron microscopy.

The differential interaction scoring approach has identified virus-specific shared interactions.

Researchers have developed and compared three different coronavirus-host protein-protein interaction maps to identify and study the molecular mechanism of pan-coronavirus. They used a quantitative difference interaction scoring (DIS) approach to identify virus-specific shared interactions between different coronaviruses. They also systematically performed intracellular localization analysis using tagged viral proteins and antibodies targeting specific proteins.
SARS-CoV-2.

Researchers have identified key molecular mechanisms and potential therapies by combining genetically validated host factors with genetic data and medical records from COVID-19 patients. Their results showed that when individually expressed viral proteins were compared to the localization of the same protein during infection, the protein localization could be different. This can be due to a number of factors, including mislocation due to tagging, altered localization by interacting partners, and the intracellular compartment specific to infection.

“To see if these associations have therapeutic value requires replication and further work in other patient cohorts, but at least tested from real-world clinical use using protein network analysis. We have shown strategies that can make possible predictions. Information. “

These differences are important warnings of host-viral interaction studies performed using tagged expressed proteins. However, this work and previous studies show how these observations are important for identifying host-targeted processes and suitable drug targets. The authors feel that their results are important enough to deserve further molecular and clinical studies.

An integrated approach to analyzing and understanding coronavirus infections

Overall, researchers describe a collaborative and integrated approach to studying and interpreting coronavirus infections and identifying targeting mechanisms that may be highly relevant to other coronavirus family viruses. did. They are hosts infected with SARS-CoV-2 and other coronaviruses using a variety of techniques from proteomics, virology, cell biology, genetics, biochemistry, structural biology, clinical and genomic information. It provided a complete picture of the interaction with cells. Researchers are strongly encouraged to use such an integrated approach to study other infectious pathogens and other disease areas.

“A careful analysis of the relative benefits and risks of typical antipsychotics should be done before considering prospective studies or interventions, but these data and analyzes are based on real-world molecular information for the treatment of COVID-19. It shows how it translates into the effects of. Eventually it could be applied to other illnesses. “