Cell: Identification of key host molecules hijacked by coronavirus to infect human cells

In a new study, researchers from the Gladston Institute and the Chan-Zuckerberg Biological Center in the United States worked with scientists at the University of California, San Francisco, and Synthego to identify key molecular processes in human cells in which coronavirus is used to survive.
they report that targeting these processes with drugs can not only treat COVID-19 infections, but also other existing and future coronavirus.
results were published online December 8, 2020 in the journal Cell under the title "Genetic screens identify host factors for SARS-CoV-2 and cold common coronaviruses".
, from Cell, 2020, doi:10.1016/j.cell.2020.12.004 Co-author and director of the Glaston Virology Institute, said, "What's unique about our study is that we're not just looking at SARS-CoV-2, we're looking at other coronavirus at the same time."
gives us a good understanding of drug targets that can widely suppress many coronavirus.
Andreas Puschnik, co-author of the paper and lead researcher at the Chan-Zuckerberg Center for Biological Sciences, said, "There have been multiple coronavirus outbreaks, so it's clear that the coronavirus family has high epidemic potential."
COVID-19 is not the last coronavirus infection we have to face.
" comparison and comparison of coronavirus Like all viruses, coronavirus can only grow in the host cell, they rely on the host cell molecules for proliferation.
, the authors hope to target the human molecules the virus is used to survive, not the components of the virus itself.
in the new study, they infected human cells with SARS-CoV-2 or two other coronavirus (HCoV-229E and HCoV-OC43) that cause the common cold, all three of which kill them.
, they used CRISPR-Cas9 gene editing techniques to mutate these cells and studied which mutations made them less susceptible to these coronavirus.
Puschnik explains, "We infer that the few cells that survive these infections are probably the host molecules that these coronavirus use to infect them or proliferate."
" results are not surprising.
, for example, SARS-CoV-2 is known to require a human ACE2 subject to enter human cells.
, cells with mutations in the ACE2 gene are no longer infected or killed by SARS-CoV2.
, however, other findings were unexpected.
the authors found that certain genetic mutations prevented the three coronavirus from successfully infecting and killing human cells.
these mutations occur in genes known to control the balance of two lipid molecules in human cells--- cholesterol and phosphatidylinotol phosphate (PIP---
is needed for some viruses to enter cells, but when the study began, it had not yet been studied in the context of coronavirus.
, PIP is known to play a role in forming viruses that are often used to enter small vesicles inside and around cells, but it has not previously been directly associated with SARS-CoV-2.
path to drug development In order to verify the importance of cholesterol and PIP-related genes to coronavirus infections, the authors designed human cells that lack these genes completely and infected them with coronavirus.
cells that lack these genes are protected from the three coronavirus infections.
, these cells are less susceptible to any kind of coronavirus infection when they use existing compounds to disrupt the balance of PIP or cholesterol.
these results suggest that targeting cholesterol or PIP may be a promising strategy against multiple coronavirus.
The traditional view for viruses is that we design drugs for unique virus targets, which means that every time there is a new virus, it takes time to develop a drug," Ott said.
if we can develop some broader antiviral drugs that target host cell molecules, it will go a long way toward better responding to future pandemic viruses.
" However, not all of the three coronavirus studied had the same results.
human molecules needed for SARS-CoV-2 infection are not needed for these two common cold coronavirus, and vice versa.
findings may help explain what makes SARS-CoV-2 more deadly than the other two coronavirus.
more research is needed to test the effectiveness of drugs targeting PIP and cholesterol and whether they can effectively stop the growth of coronavirus without dangerous side effects.
the authors also wanted to use repeated screening using other coronavirus -- including SARS-CoV and MERS-CoV -- to determine how common the new targets they identified were.
: 1.Ruofan Wang et al. Genetic screens identify host factors for SARS-CoV-2 and common cold coronaviruses. Cell, 2020, doi:10.1016/j.cell.2020.12.004. 2.Researchers identify critical molecules that coronaviruses hijack to infect human cells