New York City, January 27 ANI A new study has reported the discovery of a molecule with significant potential to disable the COVID 19 virus.
The study was published in the Journal of Chemical Information and Modeling''.
The molecule was identified by high-throughput virtual screening a search through a library of 6.5 million in-stock compounds that could be scaled up for drug production. The team used computer-based molecular docking studies to identify molecules that could bind to certain targets on the virus's main protease Mpro, an enzyme that the virus uses to make copies of itself.
They also conducted high-throughput laboratory screening experiments, structural studies, and molecular dynamics simulations to learn how these potential inhibitors and the enzyme interact. The goal was to find molecules that could jam up the enzyme's function, which would stop the virus from replicating.
The computational team, which included scientists from the Computational Science Initiative CSI at DOE's Brookhaven National Laboratory, identified 72 candidate molecules with the potential to inhibit Mpro. Other teams ran laboratory experiments that tested that molecules' ability to inhibit the virus.
Structural studies using, for example, x-ray crystallography revealed how the candidate molecules fit together with the virus enzyme. Other computer-based simulations provided details about how those interactions affect the enzyme.
The paper described how the most promising candidate, known as MCULE - 5948770040, was bound with Mpro and changed its shape in a way that inhibits the enzyme's function. Future experiments will look at whether the molecule can be developed into a new drug for treating COVID 19.
Scientists from Brookhaven's CSI have played a key role in generating and analyzing large volumes of data that led to scientific insight, said Shantenu Jha, one of the corresponding authors on the paper who has a joint appointment with Brookhaven and Rutgers University.
He said that CSI folks also established a software infrastructure' to support large-scale computations.
Given the urgency of the epidemic, this was a very high-intensity project with a great level of learning while doing, Jha noted.
CSI's Hubertus Van Dam, another study co-author, agreed that he was inspired by tackling a new set of problems with a new set of methods in a large team. The team included researchers from five national laboratories and four collaborating universities that are supported by the DOE Office of Science through the National Virtual Biotechnology Laboratory NVBL NVBL, a consortium of DOE national laboratories that are focused on responding to COVID 19 with funding provided by the Coronaviruses CARES Act.
Kerstin Kleese Van Dam, the director of CSI at Brookhaven, served as the leader of Brookhaven's role in the NVBL medical therapeutics project.
A key weapon in our arsenal in the fight against COVID 19 is medicines to treat those infected, she said.
She added that the NVBL medical therapeutics project brought together DOE scientists and key experimental and computational facilities to discover new COVID treatments.
She concluded that this paper describes not only some of our successes but also gives a glimpse of the scientific ingenuity needed to make those exciting discoveries possible.