Pioneering a ‘Staple’ Approach for Treating COVID-19
April 09, 2020
to bar the coronavirus (COVID-19) from entering cells — thereby preventing
infection and averting transmission of the virus — are among the most promising
treatment approaches to COVID-19. Everything from antibodies to specially made
snippets of RNA are being mustered in the effort to develop a safe and
effective coronavirus blocker. (RNA is a molecular messenger within cells.)
approach notable for its ingenuity — and the fact that it has proven successful
in other types of viruses — has been pioneered by Loren
Walensky, MD, PhD, a pediatric oncologist and chemical biologist at
Dana-Farber/Boston Children’s Cancer and Blood Disorders, and his colleagues.
Using what are known as stapled peptides, the approach seeks to jam the
“landing gear” that the virus uses to fuse to the cells of the human
virus consists of a short coil of RNA wrapped in a protein envelope that
includes stalk-like projections resembling points on a crown. A key surface
protein “contains a series of coiled sections known as alpha helices,” Walensky
explains. “The virus deploys three of these helices to overlap with three
others to form a six-helix bundle that fuses with the human cell membrane,
allowing the virus to penetrate and infect the cell.
approach is to make a ‘decoy’ helix that slips between the two groups of
helices to prevent the bundle from assembling,” he notes.
consists of a stapled peptide. Peptides are short chains of amino acids — not
long enough to be full-fledged proteins — but can interact with proteins to
modulate a variety of cellular functions.
advantage of using peptides is that they are nature’s solution to targeting
proteins,” Walensky remarks.
attempts to use natural peptides as therapies faced obstacles because the peptides
can lose their shape and get degraded rapidly once injected into the body.
chemistry-based solution was to reinforce peptides with hydrocarbon “staples.”
In 2010, Walensky and his associates showed that a stapled peptide could
effectively target the fusion apparatus used by HIV-1, the virus that causes
many other viral families — including those of the RSV, SARS, MERS, and Ebola
viruses, as well as the novel coronavirus — use the same fusion mechanism,
there are valid reasons for believing this approach will work against them as
previously demonstrated for the respiratory syncytial virus (RSV), our newly
designed stapled peptides targeting the novel coronavirus’ helical bundle may
be effective both as a way to prevent infection as well as to block the spread
of infection to the lungs in people with established infection,” Walensky
are currently underway to test the Walensky lab’s peptides against the novel
coronavirus that causes COVID-19.