COVID-19, a variant of SARS-COV-2 virus, sent the world into a spiral after its unprecedented and swift spread to 229 countries and territories, from late-2019 to early 2020. While vaccines were discovered to help our bodies produce antibodies to protect against the virus, the vaccines were temporary and needed boosters.
This was caused by how the vaccines acted on the virus. The simplest virus structure is comprised of a nucleic acid enclosed by a protein coat, called the capsid. The nucleic acid are made of either DNA or RNA, responsible for coding the virus to perform its specific function.
basic structure of a virus
However, many viruses build off of this and are therefore, more complicated. On the SARS-COV-2 virus, there is an essential component called the spike protein which aids in binding to human cells to infect them, enabling the virus to replicate and spread. Due to their vital role, most COVID-19 treatments target the spike proteins.
There is one problem that prevents the vaccines from being more effective: the spike protein’s tendency to mutate. When the proteins attack a human cell, they change into an “open structure”, where they reveal a binding site called RBD that attaches to the ACE2 protein on the human cell. Afterwards, the virus begins to infiltrate the cell. Some vaccines are designed to affect the RBD site so the virus cannot bind in the first place.
However, new COVID-19 strains have been coming out with a mutation on the RBD site that dilutes the effectiveness of vaccines. Scientists believe with further mutations, the RBD site will be completely immune to the vaccines. Nevertheless, a solution has been proposed: targeting the “Achilles’ heel” on the spike proteins. There is a certain pocket on the protein that, when blocked, prevents the protein from changing into its open structure, effectively stopping it from binding to a human cell. There are a few possible ways to block the fold. Free fatty acids (FFAs) are a possibility, however they bond weakly.
According to the the official research paper, published by the team through the American Chemical Society, inspiration was taken from the FFAs and used virtual screening to identify a series of compounds that would better bind and block the target than the fatty acids.
Virtual screening is a method used to scan over libraries of small molecules and determine a handful that would best bind to the specified drug target based on each molecule’s specific structure and function.
molecules identified by the screening
The team then carried out more experiments with modified versions of molecules to test ability to bind, effectiveness, etc. Not only can this improve COVID-19 treatment, it has also advocated for virtual screening in the field of drug discovery, considering its role in the team’s project. The small molecules discovered that were most suited already were LA, OA, and ATRA which show low binding affinity. However, with structural modifications, the team may be able to enhance them to fit their needs and create a more permanent COVID-19 treatment. The team of researchers continue to work on finding the best cure and prevention for the virus that dramatically altered the lives of at least hundreds of millions of people.