my country's new crown special medicine may be a "dark horse" to prevent mutant strains!
◎Reporter Zhang Jiaxing
One injection of 0.6 grams of antibody, one injection for one month!
At the Beijing Ditan Hospital, people infected with the new crown received a “sympathetic medication” independently developed by my country called DXP-604.
After use, the viral load in the patient's body dropped significantly, and the symptoms such as wheezing, decreased taste and smell improved significantly, and some patients have recovered and been discharged from the hospital.
The first-line clinical performance makes DXP-604 hopeful to become the "dark horse" of the new crown specific drug. What is more unique is that when most other drug candidates use "a pair of antibodies" to prevent the escape of the new coronavirus, DXP-604 achieves a "single antibody". Prevent mutant strains.
The drug was jointly developed by Peking University's Xie Xiaoliang team and Danxu Biology.
On November 16, a reporter from Science and Technology Daily interviewed Xie Xiaoliang, the leader of the R&D team-Li Zhaoji Chair Professor of Peking University.
He said that the feature of replacing the "antibody pair" with a single antibody will make its production cost less than one-third of other drug candidates. At present, Danxu has reached a cooperative development intention with Sinopharm Group Sino Biotech.
What does the new crown drug look like?
DXP-604 is a neutralizing antibody drug, and its prototype is the neutralizing antibody that exists in the human body.
After fighting with the new coronavirus, the patient's own immune mechanism will select the neutralizing antibodies that "will fight".
This step is considered a "sea election", and the special medicine is among them.
The problem is, the special effects must be chosen among the best!
In the past, it took years to select antibodies, because the number of neutralizing antibodies was huge, tens of thousands, and trace amounts could not be captured.
The invention of high-throughput single-cell gene sequencing technology allows researchers to quickly search cell by cell.
As a pioneer in single-cell genomics, Xie Xiaoliang's laboratory has leading international technological advantages.
In the global competition of research and development, antibody drug research and development is like sand and stone panning for gold. The more stones are turned over, the more likely it is to capture the strongest antibodies.
The Peking University team achieved the screening of more than 8,000 candidate antibodies in just a few months.
The data shows that based on multiple screenings, the Peking University team screened out a number of specific drug candidates. DXP-604 is the best among them.
This is why the drug only needs 0.6 grams for treatment, and it can be even less.
"We are doing a climbing experiment, and it is likely that 0.3 grams will be enough." Xie Xiaoliang said.
How to prevent the virus from escaping?
The research and development of new crown drugs is changing rapidly!
Over the past 22 months, global resources have gathered rapidly; in the past few months, a large number of drug candidates have suffered painfully due to frequent virus mutations.
The repeated and complicated new crown epidemic has put forward higher requirements for new crown specific drugs to cope with mutation.
Antibody pairing is a common strategy. Two antibodies have different binding sites to the virus. When one antibody fails, the other can also inhibit the virus. For example, both Regeneron and Eli Lilly use an antibody pair, but both have one antibody. Escaped by Delta Strain.
"We had a drug candidate, DXP-593, which was escaped by the Delta strain." Xie Xiaoliang said that its drug effect is very high, but it exerts huge evolutionary pressure on the virus. The amino acid sequence of the new coronavirus changes and the antibody fails.
The cost of escape is painful.
Xie Xiaoliang did not deny that: nearly 100 million yuan in research and development funding has been in vain.
How to do?
Xie Xiaoliang's team originally planned to use DXP-593 and DXP-604 together, but a new research method has brought unexpected surprises. DXP-604 alone can prevent the mutant strain.
"We have recently developed a high-throughput yeast display technology to test all the more than 4,000 possible single-point mutations in the receptor binding domain of the new coronavirus protein (S protein) one by one with neutralizing antibodies." Xie Xiaoliang said, Xin The technology can clearly show the possibility of the escape of the new coronavirus among different antibody drugs.
The "escapes" that appeared in the real world have been verified one by one. For example, the test results of the candidate drugs of the two multinational pharmaceutical companies "Zhengji" also showed that they would escape at the delta mutation site.
The test result of DXP-604 was unexpected. It gave the new crown virus a "dilemma": either it did not mutate, it was neutralized by DXP-604, or it mutated "out of the circle", but it will change so much that it is difficult to recombine. On human cells.
It is DXP-604's "killer feature" to let the new crown virus fall into the situation of "waiting for death without changing, but looking for death".
In order to verify the results, the team also cooperated with a third-party team to use the fake virus platform to make a real mutation escape "battle", and the results were consistent.
What is the listing plan for Super antibody?
"It is the Super antibody we are looking for." Looking back at the twists and turns along the way, Xie Xiaoliang concluded that antibody specific drugs are not all-round. The location is just right, and in the end it is "Tai Chi" that makes the virus desperate.
"We have a full-spectrum antibody that can resist all single-point mutations in the RBD region, enough to neutralize all existing mutant strains, and to the greatest extent will not be escaped by future mutant strains." Xie Xiaoliang said.
Regarding the clinical trial and timetable for the launch of DXP-604, Xie Xiaoliang introduced that the domestic phase II clinical trial is being carried out, and the Sinopharm Group China Biotech has been in contact to advance the overseas phase II/III clinical trials.
Beijing has approved DXP-604 as a "sympathetic drug" for clinical treatment in Beijing Ditan Hospital. Currently, the clinical trials and "sympathetic drug" drugs are all produced by WuXi Biologics.
Xie Xiaoliang expressed the hope that my country's self-developed new crown drug will be available as soon as possible.