British corona variant that came to Korea… Some treatments might make it useless

An electron micrograph of a virus that causes a novel coronavirus infection (Corona 19). [미국 국립알레르기감염병 연구소]

An electron micrograph of a virus that causes a novel coronavirus infection (Corona 19). [미국 국립알레르기감염병 연구소]

A new coronavirus (Corona 19) strain, first appearing in the UK and spreading around the world, may neutralize some antibody treatments.

Monoclonal Antibody Therapy STE90-C11
Attack target protein amino acid changes
S protein-antibody binding capacity is 1 in 160
Antibodies produced by vaccines appear to be different

This study is only for specific antibodies that attack specific regions of the viral spike protein, but further studies are needed on common antibodies made in the human body through vaccines.

However, Corona 19 vaccine manufacturers and related experts predict that the vaccines currently being distributed or under development will work sufficiently against the UK’s strains (variants).

On the 27th (local time), Ph.

This is an analysis of how the RBD (receptor binding site), a part of the viral spike protein, interacts with other proteins such as receptors (ACE2, angiotensin converting enzyme 2) in human cells using molecular physics methods.
Protein interaction changes were simulated based on the difference in binding energy.

Higher binding to human cell receptors

Analysis showed that the N501Y mutant strain found in the UK enhanced the interaction between the viral spike protein and ACE2, and increased the avidity between the two.

Amino acid 501 is one of the amino acids that directly contact ACE2 in RBD, and the British mutation N501Y is that the 501st amino acid of RBD is replaced from asparagine (N) to tyrosine (Y).

As the amino acid changes, the virus’s RBD has a deeper access to the center of the receptor, allowing it to bind better, Pratev explains.

Combination of British variant virus and human receptor.  The left S1 RBD refers to the receptor binding site of the viral spike protein, and the right hACE2 refers to the human receptor, angiotensin converting enzyme 2.  The red circle in the middle indicates the position of tyrosine (Tyr), the 501st amino acid of RBD.  Source: University of Texas, Ph.

Combination of British variant virus and human receptor. The left S1 RBD refers to the receptor binding site of the viral spike protein, and the right hACE2 refers to the human receptor, angiotensin converting enzyme 2. The red circle in the middle indicates the position of tyrosine (Tyr), the 501st amino acid of RBD. Source: University of Texas, Ph.

On the other hand, this variant of RBD was analyzed to have less interaction with the STE90-C11 antibody being developed by a German company as a monoclonal antibody treatment.

In particular, due to the N501Y mutation, the binding force between RBD and STE90-C11 was significantly reduced to 1 in 160.

“The results of this analysis are likely to decrease the efficacy of the STE90-C11 antibody against the British strain,” Pratev said.

Combination of antibodies with spike protein from the British variant virus.  The left is the receptor binding site (RBD) of the spike protein, and the right is the STE90-C11 being developed as a monoclonal antibody.  The green circle at the bottom of the middle is the 501st amino acid of RBD, where the STE90-C11 antibody binds.  Source: University of Texas, Ph.

Combination of antibodies with spike protein from the British variant virus. The left is the receptor binding site (RBD) of the spike protein, and the right is the STE90-C11 being developed as a monoclonal antibody. The green circle at the bottom of the middle is the 501st amino acid of RBD, where the STE90-C11 antibody binds. Source: University of Texas, Ph.

However, Dr. Pratev’s analysis is limited to specific antibodies that attack only specific regions of RBD.

This is not evidence that other antibodies made in the human body through vaccination do not block the British strain.

In the case of vaccines that inject viral antigens into the human body, the human body directly makes various antibodies, whereas in the case of monoclonal antibody treatments, specific antibodies are made.

STE90-C11 antibody is a monoclonal antibody treatment produced in large quantities using the bacteriophage technique, and it was published in a paper earlier this month and received attention.

Even if only one amino acid is changed, the binding power increases by 3 times.

On the 27th, citizens wearing masks are walking in the Aoyama shopping street in Tokyo, Japan.  Japan banned all non-resident foreigners from entering the country until the end of January of the new year as a precaution against the coronavirus strain from the UK.  It spread all over England.  AP=Yonhap News

On the 27th, citizens wearing masks are walking in the Aoyama shopping street in Tokyo, Japan. Japan banned all non-resident foreigners from entering the country until the end of January of the new year as a precaution against the coronavirus strain from the UK. It spread all over England. AP=Yonhap News

Meanwhile, in a separate study published in medRxic, a research team from Sichuan University in China released the analysis result that “Even if only one amino acid of the coronavirus RBD is changed, the binding ability with the receptor, ACE2, can be greatly changed.”

They also analyzed the avidity through simulation of replacing amino acids in RBD. In the case of 6 out of 9 hypothetical mutations, the binding affinity was higher than before mutation.

In particular, in the case of the hypothetical mutant Q493M, the binding affinity was tripled.
This means that when amino acid 439 is changed from glutamine (Q) to methionine (M), the virus can bind to human cell receptors much better.

The Sichuan University research team also analyzed 501, the major mutation site of the British variant, but analyzed a hypothetical mutation in which the 501th amino acid was replaced by valine (V) instead of tyrosine (Y) in asparagine (N).
It is believed that this is because research was conducted before the British variant was known.

As a result of the analysis, unlike the British variant, the N501Y mutation, the N501V mutation did not have a particularly high avidity.

Reporter Kang Chansu [email protected]


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