Utilizing computer modeling, the group evaluated a library of little particles, looking for ones that could slip into this pocket and stick securely to the spike protein, keeping it in the closed shape. The researchers then used surface plasmon resonance and other strategies to assess analogs of these molecules for enhanced binding and solubility. The resulting substances, which can bind to spike proteins from the original coronavirus along with the omicron BA.4 version, could act as a beginning point for developing broad-spectrum treatments for COVID-19, the team says.
Reference: “In Silico Discovery of Small Molecule Modulators Targeting the Achilles' ' Heel of SARS-CoV-2 Spike Protein” 8 February 2023, ACS Central Science.DOI: 10.1021/ acscentsci.2 c01190.
The authors acknowledge assistance from the Beijing Municipal Science & & Technology Commission and Tsinghua University.
The notorious spike proteins on the surface area of SARS-CoV-2 aid it bind to and get in human cells. Since of their essential role in spreading infection, these spike proteins are one of the main targets for COVID-19 vaccines and treatments. In the “closed” structure, this RBD section is tucked inside the spike protein and cant bind to human cells. Utilizing computer modeling, the team screened a library of little particles, looking for ones that might slip into this pocket and stick firmly to the spike protein, keeping it in the closed shape.
Some little molecules can lock SARS-CoV-2 spike proteins in a harmless closed configuration (left) rather of the transmittable open setup (right). Credit: Adapted from ACS Central Science 2023, DOI: 10.1021/ acscentsci.2 c01190.
Utilizing Small Molecules To Keep SARS-CoV-2 Closed for Business.
The infamous spike proteins on the surface area of SARS-CoV-2 aid it bind to and go into human cells. Due to the fact that of their important function in spreading infection, these spike proteins are among the main targets for COVID-19 vaccines and treatments. However those treatments gradually lose efficiency when specific sections of the spike proteins mutate. Now, scientists report in ACS Central Science that they have found small molecules that successfully target other sections that alter less.
Spike proteins change shape when they assault a cell. In their “open” structure, they expose an area known as the receptor-binding domain (RBD) so it can connect to the ACE2 protein on human cells. In the “closed” structure, this RBD segment is tucked inside the spike protein and cant bind to human cells.
To get around this issue, other, less mutation-prone parts of the spike protein might be targeted rather. One possibility is a pocket in the spike protein that has been dubbed the Achilles heel of the infection.
