Combating COVID-19: Generic Antibodies Can Be Retrained to Recognize SARS-CoV-2

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 TOPICS: BiochemistryInfectious DiseasesPharmaceuticalsPublic HealthUniversity Of Illinois At ChicagoVirology



Double-faced peptide-based boosters are computationally designed to permit the recognition of SARS-CoV-2 (grey, schematic) by hepatitis B antibodies. One booster face made from ACE2-mimic peptides (red) can bind to the receptor-binding domain of SARS-CoV-2 (blue). the opposite booster face composed of a hepatitis B core-antigen (orange) can target the hepatitis B antibody fragment (green). This approach can provide an inexpensive and efficient neutralization of emerging pathogens by generic antibodies. Credit: UIC

The SARS-CoV-2, the new coronavirus behind the present pandemic, infects humans by binding its surface-exposed spike proteins to ACE2 receptors exposed on the cell membranes.

Upon a vaccination or a true infection, it takes several weeks before the immunity develops antibodies that will selectively bind to those spike proteins. Such antibody-labeled viruses are neutralized by the natural killer and T cells operated by the human immunity.

An alternative approach to training the immunity response is obtainable by researchers at the University of Illinois Chicago and California State University at Sacramento who have developed a completely unique strategy that redirects antibodies for other diseases existing in humans to the spike proteins of SARS-CoV-2.

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In their study published by the Journal of chemistry Letters, the team proposes using peptide-based double-faced “booster” inhibitors, with one face binding to the spike proteins of SARS-CoV-2 and therefore the other face binding to generic hepatitis B antibodies.

“Once the SARS-CoV-2 viruses become labeled by the hepatitis B antibodies via intermediate boosters, the viruses are going to be neutralized. This universal approach allows a dramatic shortening of the reaction time upon real infections, which may be critical in certain patients or conditions,” said Petr Král, UIC professor of chemistry, physics, pharmaceutical sciences, and chemical engineering, and senior author on the paper.

Král and Yanxiao Han, who recently earned a Ph.D. in chemistry at UIC and is that the first author on the paper, believe the study could provide guidance within the preparation of generic therapeutics against emerging pathogens with the combined advantages of small-protein and antibody therapies.

“The dramatic impact which novel viruses can wear humans might be fast mitigated within the absence of their vaccination if generic antibodies present within them are temporarily retrained to acknowledge these viruses,” the researchers wrote.

In a study published last spring, Král and Han extracted different peptides from ACE2 that interact directly with the viral spike protein.

“We investigated potential COVID-19 therapeutics using computer simulations supported the X-ray crystal structure of the receptor-binding domain of SARS-CoV-2 when it's sure to ACE2,” Král said. “Similar to our latest study, identifying these sorts of inhibitors could lead on to new treatments to combat the coronavirus.”

Reference: “Retrained Generic Antibodies Can Recognize SARS-CoV-2” by Yanxiao Han, Katherine D. McReynolds, and Petr Král, 1 February 2021, Journal of chemistry Letters.

DOI: 10.1021/acs.jpclett.0c03615

The co-author of the paper is Katherine McReynolds of California State University at Sacramento.

This work is supported by funding from the UIC Center for Clinical and Translational Science.

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