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April 12, 2020 / / -- University of Toronto researcher Sachdev Sidhu and his colleagues are designing antibody molecules that can mesmally damage the virus in the body before the new coronavirus invades cells.
researchers at the Donnelly Center for Molecular and Biomeanthratic Research are part of a team that recently received federal funding from the Canadian Health Research Association through the second round of emergency COVID-19 funding.
Sidhu has led a different team that has received support in the first round of federal funding.
goal of this project is to design antiviral drugs to stop the virus from replicating.
Through our two funding programs, we are working to develop molecules for viruses inside and outside human cells to prevent viruses from entering," said Sidhu, a professor of molecular genetics at the School of Medicine.
: This latest funding project, led by Professor James Rini of the Department of Molecular Genetics and Biochemistry at the University of Texas, aims to produce effective antibodies to the virus before it causes damage.
these antibodies are naturally produced by the body at the time of infection, but the researchers hope to strengthen the immune system by injecting them, thereby shortening the duration of the infection and reducing the severity of the disease.
previously helped determine how antibodies bind to and inactive the SARS virus.
SARS virus is a coronavirus that broke out more than 15 years ago.
, a professor in the Department of Molecular Genetics and an HIV virologist, is also on the team, specializing in the treatment of viral RNA.
these antibodies will be designed to prevent the formation of spiked so-called S proteins on the surface of the virus.
these spikes are locked in a protein called ACE2 on the surface of human cells, which enters the cells.
the virus particles with synthetic antibodies should prevent these stings from binding to ACE2.
Sidhu and Rini will also design antibodies that bind to ACE2 so that they are not infected with the virus.
type of engineering immunity exceeds the body's natural immune system because antibodies against its own proteins have been filtered out.
if successful, the method could allay concerns about a virus mutation that would invalidate the drug against emerging strains of the virus because the host protein ACE2 does not change over time.
Sidhu's team has developed an advanced technology called phage display that can quickly manufacture and select human antibodies with the required biological properties, including the S protein that blocks the virus.
the past decade, his team has produced hundreds of antibodies with therapeutic potential, some of which have entered clinical development through affiliates and large pharmaceutical companies.
the team has shown that both methods can successfully suppress the virus -- they have developed antibodies that target the mediator of the Ebola virus and human host receptors that target the Hantan virus.
addition, other studies have shown that antibodies can target SARS.
In the phage show, a tiny bacterial virus called phage was instructed to produce a large number of different antibodies, and the team will select antibodies that can kill viruses in human cells, which will then be tested in mice and eventually in patients.
in mice could begin in three to six months, said Sidhu, a research student at the school.
in addition to making antibodies against new viruses from scratch, the researchers will modify existing SARS-blocking antibodies to attack SARS-CoV-2 and provide an additional avenue for developing therapeutic drugs.
given the global spread of the virus, it has the potential to spread in populations like seasonal influenza.
, like the flu, it can mutate into new strains to evade access to immunity and vaccines being developed.
by producing a different set of antibodies, the researchers aim to take a step ahead of the virus to contain it.
Sidhu said: "Our advances in antibody engineering, as well as the acquisition of a complete genome of the COVID-19 virus and its associated viruses, provide us with an opportunity to tailor therapeutic antibodies to scale and speed, which was not possible a few years ago.
, our goal is to optimize our approach so that the evolution of new drugs can keep up with the evolution of the virus itself and provide new and effective drugs to respond to new outbreaks.
" () Reference: Researchers developing antibodies 'neutralize' novel coronavirus before it invades cells.