A new study using human genetics suggests that researchers should prioritise clinical trials of drugs that target two proteins to manage Covid-19 in its early stages.
Based on their analyses, the researchers are calling for prioritising clinical
trials of drugs targeting the proteins IFNAR2 and ACE2.
The goal is to identify existing drugs that can be re-purposed for the early
management of Covid-19, said the team from Veterans Affairs Boston Healthcare
System in the US in a paper in the journal Nature Medicine.
IFNAR2 is the target for approved drugs often used by patients with relapsing
forms of the central nervous system disorder multiple sclerosis.
The researchers believe the most promising ACE2 therapy against Covid-19 is a
drug that was developed before the pandemic began and has been evaluated in
clinical trials to reduce inflammatory response in patients with severe
respiratory disorders.
"When we started this project early last summer, most COVID-19 trials were
being done on hospitalised patients," said Dr Juan P Casas, a physician
epidemiologist at the Veterans Affairs Boston Healthcare System.
"The problem we tried to overcome is how to identify if existing drugs,
either approved or in clinical development for other conditions, can be
repurposed for the early management of Covid-19," he added.
ACE2 is highly relevant to Covid-19 because the coronavirus uses that protein
to enter human cells.
The most promising ACE2 therapy against COVID-19 is the drug APN01, which
mimics the protein.
The drug works by confusing the coronavirus so it attaches to the drug instead
of the ACE2 protein in the human cell.
Positive evidence is emerging from small clinical trials on the effectiveness
of APN01 in COVID-19 patients, especially those that are hospitalized.
"Hence, if our genetic findings are correct, there's a need to test this
strategy in clinical trials in COVID-19 outpatients," Casas noted.
The researchers also showed that people with a certain variant of IFNAR2 had
less chance of being hospitalised due to COVID-19, compared to people without
the variant.
Casas said he sees a continued need for drugs to treat people in the early
phase of COVID-19, despite the ongoing worldwide vaccination campaigns.
"This is largely due to two reasons," he says. "First, it will
take some time to achieve the high levels of vaccine coverage needed to create
herd immunity. In addition, certain coronavirus variants are emerging that seem
to lead to a reduced vaccine efficiency. We are not yet in the clear."
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