Using neutron experiments and computer simulations, researchers delved into how some of the proposed COVID-19 drug candidates behave at the molecular scale when exposed to water. The results could help experts understand the mechanisms by which drug molecules have the potential to mitigate the impact of viral infection.
Scientists can analyze the molecular dynamics of drug molecules to better understand their interactions with target proteins in human cells and their potential for treating certain diseases. Many studies examine drug molecules in their dry, powder form, but less is known about how such molecules behave in a hydrated environment, which is characteristic of human cells.
Using neutron experiments and computer simulations, a team of researchers from the Department of Energy’s (DOE) Oak Ridge National Laboratory (ORNL) delved into how some of these drugs behave at the molecular scale when exposed to water. The scientists conducted this research using neutron scattering instruments at the ORNL Spallation Neutron Source (SNS).
They found that certain parts of the molecules were able to move more easily once hydrated. This factor could influence how efficiently a drug takes on shapes associated with different biological functions, such as binding to a target protein and inhibiting viral activity. The results of this project, now published in ACS Omega and the Journal of Physical Chemistry Letters, could help experts understand the mechanisms by which drug molecules have the potential to mitigate the impact of viral infection.
«The human body is approximately 60 percent water. When drugs are in our bodies and interacting with water molecules, they are not going to move the same as when they are in a crystalline state,» said Matthew Stone, an ORNL instrument scientist involved with the study. «Having a fundamental understanding of how the drugs might act in human bodies could help scientists determine which molecules are effective against the virus.»
The study analyzed three molecules: remdesivir, an antiviral drug developed to treat the Ebola virus disease; dexamethasone, a steroid commonly used for autoimmune and inflammation conditions; and hydroxychloroquine, an immunosuppressant drug created for preventing and treating malaria. The team’s early work focused on hydroxychloroquine, when it was being investigated as a COVID-19 treatment, but as new candidates were identified by the medical community, the project shifted to studying remdesivir and dexamethasone.
Story Source: Materials provided by DOE/Oak Ridge National Laboratory. Original written by Olivia Trani. Note: Content may be edited for style and length.