Can reduce 99% of the new crown virus load! "Science" reports a new hope of fighting the epidemic

When it comes to controlling the new crown epidemic, many people think of vaccines

Today, "Science" magazine reported the progress of an innovative new crown therapy

What kind of magic drug is this? Let's start with its research and development process

Sword finger key protein

Previous studies have found that after the new coronavirus enters the cells of the host, its viral genome will produce about 30 different proteins, of which 16 proteins exist in the form of "polyproteins" and must be "cut" before they can continue to exert their effects.

It is conceivable that the enzyme responsible for "cutting off" the work is the key to the infection of the new coronavirus

More importantly, the functions of these two proteases are "indispensable" to the life cycle of the virus, so they are unlikely to be like spike proteins that will mutate under the immune pressure brought by vaccines, further reducing their drug resistance.

In order to save time for drug development, the research team mentioned in the "Science" paper that they used the strategy of "old drugs and new use"-scientists first screened 1,900 drugs that are already in clinical use, looking for energy Drugs that inhibit common coronavirus infections

picture

▲A variety of old drugs have shown the ability to inhibit the new coronavirus (picture source: reference [1])

108 drugs came to the fore and were further used to test their ability to inhibit the new coronavirus

Subsequently, the researchers began to evaluate whether these 20 drugs would inhibit the key target of 3CLpro

▲Only 8 kinds of molecules can inhibit the key target 3CLpro, of which masitinib has the strongest inhibitory ability (picture source: reference [1])

Where is Masitinib sacred? According to known information, it is a c-kit inhibitor that can be taken orally.

Unique mechanism of action

Can this medicine for other diseases really inhibit the replication of the new coronavirus? In order to gain insights from the mechanism, the researchers further obtained the X-ray crystal structure of the combination of masitinib and 3CLpro

▲From the structural point of view, masitinib can block the key catalytic residues and active sites of 3CLpro (picture source: reference [1])

Considering the mechanism of action of masitinib, the researchers judged that it should be a competitive inhibitor

We also mentioned above that the new coronavirus infection of cells requires the participation of two enzymes, 3CLpro and PLpro

Finally, the researchers decided to actually evaluate the anti-coronavirus effect of masitinib in animal models

▲Animal experiment results show that masitinib can reduce virus titer and improve lung pathology (picture source: reference [1])

On the sixth day of treatment, the researchers began to analyze the effect of the treatment and found that masitinib significantly reduced the virus titers in the lungs and nose of the mice, and improved the pathological conditions of the lungs

Taken together, the researchers pointed out that masitinib can reduce the viral load by more than 99% on the sixth day of treatment!

At the end of the paper, the researchers concluded that masitinib exhibits a good viral inhibitory effect, and can reduce lung inflammation and enhance lung function

"It takes a long time for the world to be vaccinated, and the variant virus that can produce immune escape also has the possibility of making the virus ineffective," said Dr.
Nir Drayman of the University of Chicago, one of the leaders of this study.
The need for innovative anti-viruses for new
coronaviruses and new viruses that may emerge in the future continues
.
It is exciting to see the characteristics of masitinib in these two aspects .
It can target all the new coronavirus variants we tested, including the highly infectious ones.
Alpha, Beta, and Gamma variants also exhibit broad-spectrum antiviral activity and have the potential to treat many other viral diseases
.
"

"Our data show that the best results can be achieved by using masitinib in the early stages of infection.
This is the time period when antiviral drugs are most effective," said Professor Savas Tay, another person in charge of this study, "because masitinib can be simply taken orally Drug delivery, early treatment is a feasible strategy
.
In the future, we need to study its potential benefits more carefully in clinical trials
.
"

Reference materials:

[1] Nir Drayman et al.
, (2021), Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2, Science, DOI: 10.
1126/science.
abg5827

[2] AB Science announces the publication of an article in the world-renowned journal Science that confirms potential of masitinib as a treatment of Covid-19 with anti-viral activity against SARS-CoV-2 and all tested variants of concern, Retrieved July 20, 2021, from https:// -world-renowned-journal-Science-that-confirms-potential-of-masitinib-as-a-treatment-of-Covid-19-with-anti-viral-activity-ag.
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