Researchers in China report structure of the novel coronavirus bound to its human target
Adapted from the news item in the Chemical & Engineering News (C&EN)1
The structure shows the first steps of SARS-CoV-2 infection, and could help in drug discovery
March 16, 2020
Chinese researchers have now identified part of the novel cornonavirus (SARS-CoV-2) bound
to its target on human cells. It binds to the angiotensin-converting
enzyme (ACE2), an enzyme involved in blood pressure regulation. Those
of us who have high blood pressure, may be taking a a class of drugs
called ACE-inhibitors (a common drug is lisinopril). This discovery
could lead to the development of antibodies that will block the
interaction. This knowledge is also used in developing vaccines that
could prevent people from contracting the disease in future.
More details from C&EN: ACE2
is the first in a string of enzymes that convert the hormone
angiotensin into its active form. When cleaved by enzymes, angiotensin
makes blood vessels contract. The SARS-CoV-2 spike protein has two key
elements involved in infecting human cells. A string of amino acids in
the S1 subunit directly binds to the protein-cleaving part of ACE2
called the peptidase domain. The S2 subunit of the spike protein helps
the virus fuse to the human cell. The new structure shows the first of
these two events. “You have attachment, and entry. Blocking either
function can prevent entry,” Jason McLellan, a researcher from the
University of Texas says, describing how treatments could be designed to
stop SARS-CoV-2. “Ideally, you want antibodies that can target both
functions.”
The
scientists found that the protein-cleaving part of ACE2 binds the spike
through polar interactions formed from a bridge-like structure on the
enzyme. Both ends of the receptor binding domain stick to ACE2 through
hydrogen bonding and van der Waals forces, and in the middle, Zhou
describes several amino acids that interact with an asparagine and
histidine in ACE2 that may be required for the spike protein-ACE2
interaction to occur.
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