Health
Protein Structures That Help Coronavirus Replication: Which Drugs Can Block It?
Diagram of SARS-CoV-2 envelope protein E in a bundle of five helices. There is a gray water column inside. MIT
A chemist at the Massachusetts Institute of Technology determined and explained the molecular structure of the protein found in the novel SARS-CoV-2. Coronavirus Because of that COVID-19.. They reported their findings in the journal Nature Structuraland Molecular Biology.
This protein, called enveloped protein E, plays an important role in the ability of the virus to replicate itself and stimulate the inflammatory response of host cells. Researchers said that devising a way to block this pathway of the virus could reduce the pathogenicity of the virus and prevent it from replicating.
In the MIT study, researchers investigated the binding sites of two drugs that block the channels used by enveloped protein E. However, these drugs bind weakly and are not effective inhibitors of the E protein.
The lead author of this study, May Hong, has a laboratory specializing in the study of the structure of proteins embedded in cell membranes.When Pandemic Beginning earlier this year, Hong and her students decided to focus on one of the SARS-CoV-2 proteins and finally chose the E protein. It is made up of a bundle of several helical proteins.
Researchers were able to clone and purify the E protein in two and a half months. Next, it was analyzed by nuclear magnetic resonance (NMR) spectroscopy for 2 months. They found that some of the E-proteins were clustered in a bundle of five helices. The helix remains almost stationary within this bundle, creating a tight channel.
At one end of the channel, researchers have identified several amino acids that can attract positively charged ions, such as calcium, to the channel. They believe that the structure they described is a closed state of the channel. Researchers now want to determine the open structure that should reveal how the channel opens and closes.
Researchers have also discovered that two drugs, amantadine, which is used to treat influenza, and hexamethyleneamiloride, which is used to treat high blood pressure, can block the entrance to the E-channel. However, these drugs bind only weakly to the E protein. If more potent inhibitors are developed, they could be potential drug candidates for the treatment of Covid-19, the researchers said.
“It’s important to recognize and remember that even after the pandemic is over, our society must continue to vigorously carry out basic scientific research on viral and bacterial proteins. Human and economic costs are too high, “Hong said in a statement.
Source: Massachusetts Institute of Technology
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