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.”