MIT scientists have developed a drug candidate that could block the ability of coronaviruses to enter human cells. This could help develop a possible treatment for COVID-19.
The potential drug is a short protein fragment or peptide that mimics a protein found on the surface of human cells, the researchers said.
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They have shown that their new peptide can bind to and possibly defuse the viral protein that coronaviruses use to penetrate human cells. This is evident from the results published on bioRxiv, an online preprint server.
“We have a lead compound that we really want to research because it actually interacts with a viral protein as we predicted, so it has a chance of inhibiting viral entry into a host cell.”
The researchers sent samples of the peptide to employees who want to run tests on human cells.
The team started work on this project in early March after the cryo-EM structure of the coronavirus spike protein, along with the human cell receptor to which it binds, was published by a research group in China.
Coronaviruses, including SARS-CoV-2, which is causing the current COVID-19 outbreak, have many protein spikes that stick out of their virus envelope.
Studies of SARS-CoV-2 have also shown that a specific region of the spike protein, known as the receptor binding domain, binds to a receptor called angiotensin converting enzyme 2 (ACE2).
This receptor is on the surface of many human cells, including those in the lungs.
The ACE2 receptor is also the entry point of the coronavirus that caused the SARS outbreak in 2002-03.
Hoping to develop drugs that could block virus entry, Genwei Zhang, a postdoc at MIT, conducted computer simulations of the interactions between the ACE2 receptor and the receptor binding domain of the coronavirus spike protein.
These simulations showed the location where the receptor binding domain binds to the ACE2 receptor – a section of the ACE2 protein that forms a structure called the alpha helix.
“This type of simulation can give us insight into how atoms and biomolecules interact with each other and which parts are essential for this interaction,” said Zhang.
“Molecular dynamics help us narrow down specific regions that we want to focus on to develop therapeutics,” said Zhang.
The team then used the peptide synthesis technology that their laboratory had previously developed to quickly generate a 23 amino acid peptide with the same sequence as the alpha helix of the ACE2 receptor.
Your flow-based peptide synthesis machine can link amino acids, the building blocks of proteins, in about 37 seconds, and it takes less than an hour to create complete peptide molecules of up to 50 amino acids.
“We built these platforms for really fast processing. I think that’s why we’re at this point,” said Pentelute.