COVID-19 Tricks With A Fake “Shake” To Activate Coronavirus

Structural interaction of Spike SARS-CoV-2 protein with ACE2 receptor. Graphics are generated using ChimeraX software and published protein structures. Credit: Ohio State University

Scientists are developing peptides that can disable coronavirus.

Duplicate the coronavirus novel once and it can not cause cell infections, according to a new study.

Scientists have developed protein fragments – called peptides – that fit into the groove SARS-CoV-2 Protein spikes are usually used to access host cells. These peptides effectively trick the virus into a “handshake” by replicating it with native proteins on the cell surface that allow the virus to enter.

Previous research has shown that the novel coronavirus binds to receptor proteins on the surface of target cells called ACE2. These receptors are present in several types of human cells in the lungs and nose, providing many SARS-CoV-2 access pathways to infect the body.

For this work, scientists at Ohio State University designed and tested peptides similar to ACE2 that are sufficient to convince the coronavirus to bind them, an action that inhibits the ability of the virus to actually enter the cell.

“Our goal is that whenever SARS-CoV-2 comes in contact with peptides, the virus will be activated. This is because the Spike protein virus is bound to need to be used to bind to cells,” said Amit Sharma, lead author of research and assistant professor of animal biology. in the United States. “To do this, we need to get the virus while still outside the cell.”

The Ohio State Team envisions delivering these factory peptides in nasal sprays or aerosol surface disinfectants, among other applications, to block circulating SARS-CoV-2 access points and agents that prevent entry into target cells.

“With the results we have produced with these peptides, we are well positioned to step into the product development steps,” said Ross Larue, lead author and assistant professor of pharmacy and pharmacology in Ohio State.

The study was published in the January issue of the journal Bioconjugation chemistry.

SARS-CoV-2, like all other viruses, needs access to living cells to destroy them – viruses hijack the function of cells to copy themselves and cause infections. Rapid virus replication can overwhelm the host system before immune cells can develop effective defenses.

One reason coronavirus is highly contagious is because it binds strongly to ACE2 receptors, which are abundant in cells in humans and some other species. Spike protein on the surface of SARS-CoV-2 which has become the most well-known characteristic is also fundamental to the success and attachment of ACE2.

Recent advances in crystalline and microscopic proteins have allowed the creation of computer images of specific protein structures alone or in combination – such as when they bond.

Sharma and colleagues neatly examined the SARS-CoV-2 Spike and ACE2 protein images, summarizing exactly how their interactions and events and the connections needed for the two proteins could be locked. They take notice of the tail such as the spiral band in ACE2 as the focal point of the attachment, which becomes the starting point for peptide design.

“Most of the peptides we designed were based on the tape that contacted Spike,” said Sharma, who also had an appointment with the faculty of microbial infection and immunity. “We focus on creating the shortest peptides with the least important contacts.”

The team tested several peptides as “coconut inhibitors” that not only interact with the Spike SARS-CoV-2 protein, but also prevent or reduce viral replication in cell culture. Two peptides, one with minimum and larger contact points, were effective in reducing SARS-CoV-2 infection in cell studies compared with controls.

Sharma describes this discovery as the beginning of a product development process that will be followed by a team of virologists and pharmacists who collaborate on this work.

“We take a multipronged approach,” Sharma said. “With these peptides, we have identified the minimum contact required to disable the virus. In the future we plan to focus on developing aspects of this technology for therapeutic purposes.

“The goal is to neutralize the virus effectively and potentially, and now, because of the emergence of variants, we prefer to analyze our technology against emerging mutations.”

References: “Designed SARS-CoV-2 Prevention Peptide Containers” by Ross C. Larue, Enming Xing, Adam D. Kenney, Yuexiu Zhang, Jasmine A. Tuazon, Jianrong Li, Jacob S. Yount, Pui-Kai Li and Amit Sharma, 24 December 2020, Bioconjugation chemistry.
DOI: 10.1021 / acs.bioconjchem.0c00664

This research was supported by the Ohio State institutional start-up fund.

Sharma and Larue are the inventors of temporary patent applications that cover this technology. Other authors, from the University of Pharmacy, Medicine and Educational Medicine at Ohio State, are Enming Xing, Adam Kenney, Yuexiu Zhang, Jasmine Tuazon, Jianrong Li, Jacob Yount and Pui-Kai Li.

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