Irene Hartmann
08/20/2021 3:50 PM
Clarín.com
Society
Updated 08/20/2021 3:50 PM
The news is promising and has just appeared in the prestigious journal
Science
: American researchers, starting from a library of almost 2,000 antiviral drugs, selected the best candidates against Covid and found one that they are now optimistically betting on, since it generated a
reduction of more than 99% of the viral load in mice
.
It is called
masitinib
.
Although we are talking about
the preclinical phase
- that is, it was done in animals - masitinib is already being tested in humans in another investigation that is carried out in a hospital in France.
We will return to this point at the end of these lines.
Returning to the Science paper ("
Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2
", or "Masitinib is a
broad coronavirus 3CL inhibitor
, which blocks the replication of SARS-CoV-2"), It is the result of scientists from the Universities of Chicago and Duke.
The work promises not only because it confirmed a
decrease in the viral titers of the mice of up to 200 times
, but because it proved that the action to reach that reduction could exceed the particularities of the Covid variants.
That is, it would go in a different lane.
What does masitinib do in its interaction with the coronavirus?
It inhibits one of the SARS enzymes, crucial for its replication:
viral protease
.
A patient with Covid in intensive care at the Central Hospital of Mendoza.
Photo: Los Andes
"This inhibition of protease is the target of action of the drug.
It is called 'protease' because it somehow 'cuts' large proteins into smaller pieces ", explained biochemist
Jorge Quarleri
," virologist "Principal Investigator of Conicet at the Institute for Biomedical Research in Retroviruses and AIDS (INBIRS).
And, true to his field of expertise, Quarleri explained that "the therapy for HIV used today uses drugs that also inhibit the protease of that virus."
From "in vitro" to "in vivo"
The paper clarifies that, in addition to the reduction in viral titers, "there was a
reduction in lung inflammation
."
As is to be expected for a drug of this type, the authors suggest, towards the end of the paper, that the action of the drug could be
more beneficial the earlier it is administered
.
By the way, it is done
orally
, and the positive results were seen
after 6 days of medication
, with a dose similar to what a human would have received.
"It is clear that the utility they propose is for the
acute stage
of the disease," Quarleri clarified and, always hypothetically, outlined that a possible administration scheme could be "after the appearance of the first symptoms due to Covid or, perhaps, after confirming that it had been close contact of a positive case. "
In a context in which the highly contagious Delta variant advances by leaps and bounds, generating new waves of infected, it should be noted that, in the "in vitro" phase of the trial, the scientists tested the drug's efficacy against the Alpha variants ("ex" United Kingdom), Beta (ex South Africa) and Gamma (ex Manaus).
However, said Quarleri, “
the protease cannot be allowed to change or mutate too much
because that would make it lose the ability to perform its function.
That is why viral proteases are usually a desirable target of action ”.
Of course, no matter how promising the drug is, it cannot be guaranteed that any new variant will develop a “natural resistance” to the action of masitinib.
In Quarleri's words, "it remains to be seen whether the well-defined binding site of masitinib to the viral protease shows changes between variants."
One by one
The "weeding" work these researchers did is noteworthy.
"We examined a library of
1,900
clinically safe
drugs
against OC43, a human beta coronavirus that causes the common colds, and we evaluated the main successes against SARS-CoV-2," they introduce in the paper.
Of these, they selected "
20 drugs
that significantly inhibited the replication of both viruses in cultured human cells."
Then they were left with 8, which had inhibited the activity of the major SARS-CoV-2 protease (3CLpro).
And of those 8, "the most potent (they say) was masitinib, an orally bioavailable tyrosine kinase inhibitor."
With the advancement of the Delta variant, they prepare hospitalization spaces.
Photo: Reuters
The mouse test was done
12 hours after infection
.
One can assume that more "realistic" times will be considered in the clinical phase, considering that the appearance of symptoms due to Covid can take days.
For those concerned about detail, here are more clarifications from Quarleri: “The target of action of masitinib is the so-called 'major protease' (
and not a minor one that also has an important role in replication
) of the virus.
This enzyme is responsible for
cutting a protein
that the virus synthesizes during its replication within the cell. "
Why cut it off?
Because it is "it is like a 'barbecue sausage', impossible to digest. It cuts it into small proteins, which will thus be functional and allow the replication cycle to continue advancing".
Doubts and effects
Outside of the antiviral and anti-inflammatory evidence that the Science paper confirms, masitinib has been tested in humans with Covid and other pathologies, in France.
About a month ago, in fact, it was news that the AB Science laboratory, which had been conducting several studies in humans with masitinib and had had to suspend them due to the detection of a
potential risk of ischemic heart disease
(pain or discomfort in the chest recurrent), finally
managed to resume the tests
, against the commitment to apply a series of security measures that were accepted by the ANSM, basically the French ANMAT.
These trials (now resumed without, for example, patients with a cardiovascular history) include the study mentioned at the beginning of these lines, carried out with
people hospitalized for severe Covid
(phase 2), a study in people with amyotrophic lateral sclerosis (ALS), in phase 3, and one, also in phase 3, in adults with a rare immune disorder called "mastocytosis."
Swab for Covid detection.
Photo: Maxi Failla
However, Quarleri explained, "although the authors of the Science paper cite the French clinical study, they rule out that the action of the drug is due to the basis on which the French use it, who also combine the drug with another drug."
Anyway, he concluded, "the French study, perhaps by 'carambola', will give useful information to know the action of masitinib, already in a clinical phase".
The paper, the virologist opined, "is an interesting first."
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