The Nature journal publishes a comprehensive list of interacting SARS-CoV-2 viruses and human proteins

A highly innovative method using the latest technology generated a comprehensive list of interacting SARS-CoV-2 viruses and human proteins, one of which showed that viruses directly affect proteins
that regulate the human immune system.

A study titled "A Comprehensive SARS-CoV-2–Human Protein–Protein Interactome Reveals COVID-19 Pathobiology and Potential Host Therapeutic Targets," published Oct.
10 in the journal Nature Biotechnology, describes the technology.
Countless new avenues
have been opened for studying and understanding the biology behind COVID-19, as well as for identifying new treatments that target protein binding sites.

In the study, the researchers identified 23 drug candidates, each with the potential to disrupt the virus-host binding site
.
In preliminary experiments, one of the drugs was the FDA-approved β receptor blocker carvedilol for the treatment of blood pressure, which was low toxicity and very effective
in inhibiting viral infection in human lung cell lines infected with SARS-CoV-2.
In addition, an analysis of records of SARS-CoV-2 infection showed a 17 percent lower risk of SARS-CoV-2 infection in patients taking carvedilol to control blood pressure, suggesting that it inadvertently provided some protection
.

Haiyuan Yu, a professor in the Department of Computational Biology and the Weill Institute of Cell and Molecular Biology, said: "We have a new, more comprehensive view of the SARS-CoV-2 virus-human protein interaction network, which shows how viral proteins hijack human proteins and [reveals] the pathways
required for viral infection, replication and transmission.
"

Haiyuan Yu said the described method could also be applied to any virus or pathogen.

Researchers have begun using these techniques to better understand protein interactions and study treatments
for mosquito-borne Zika virus.

In this study, the researchers combined two complementary state-of-the-art methods to obtain a complete picture
of the interaction between the SARS-CoV-2 viral protein and the human host protein.
The first method uses quantitative proteomics techniques to artificially express each viral protein found in SARS-CoV-2 in human cells to see which host proteins and complexes
are recruited by the virus.
In a second method, known as Y2H, the researchers used their viral and human protein libraries
.
The individual proteins in each group are then paired together
.
This technique allows researchers to observe which pairs have affinity for each other and have contact; When they do interact, this pairing is usually short-lived
.

"Some of the most important regulatory interactions are ephemeral," Yu said
.
"A protein can only find the conjugates it needs under the right conditions, and then it separates
.
"

The technique revealed 739 high-confidence protein interactions between 579 human proteins and 28 new coronavirus-2 proteins, verified 218 known human protein interactions with new coronavirus-2, and revealed 361 new proteins
.
The researchers also found an interaction between a viral protein and a human transcription factor that is directly involved in the turn-on and off-of
immune response genes.
The finding may provide clues
to how the virus evades host immunity.

While the most relevant cells used for research come from the lungs, they are difficult to grow
in culture.
Therefore, previous studies of SARS-CoV-2 have used kidney T cells
.
For the first time in this study, the researchers used a colon cell line
.
"There is evidence that these cell lines surface expression two key marker proteins that are required for infection," Yu said, adding that kidney T cells do not express these markers
.

In the next steps, Yu and colleagues will investigate how SARS-CoV-2 regulates human gene expression, particularly as it relates to
evading immunity.
Working with John Lis, professor of molecular biology and genetics (CALS), Cedric Feschotte, professor of molecular biology and genetics (CALS), Luis Schang, professor of chemical virology (School of Veterinary Medicine), and several other groups at Cornell, they are following up on other drug candidates, some of which appear to work
.

The study was supported
primarily by the National Institute on Aging, the National Institute of General Medical Sciences, and Cornell University's SARS-CoV-2 Rapid Response Seed Fund.
The latter in collecting preliminary data to launch the study, as the influenza pandemic supported continued collaboration
.

Original:

A Comprehensive SARS-CoV-2–Human Protein–Protein Interactome Reveals COVID-19 Pathobiology and Potential Host Therapeutic Targets