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Summit researchers modelling SARS-CoV-2 find 77 potential drug candidates

Researchers at the US Department of Energy’s (DOE’s) Oak Ridge National Laboratory (ORNL) identified 77 small-molecule drug compounds that warrant further study in the fight against the SARS-CoV-2 virus. The full story, written by ORNL science writer Rachel Harken, can be found on the ORNL website.

The article notes that the research focused on SARS-CoV-2 entry point into a host cell and worked on the assumption that the virus works in the same way as other Severe acute respiratory syndrome (SARS) viruses. 

Team member and UT/ORNL CMB postdoctoral researcher Micholas Smith built a model of the coronavirus’ spike protein, based on early studies of the structure

Using the information already understood about  SARS-CoV-2 and its interaction with ACE2 receptors, ORNL researchers created a macular dynamics simulation using the GROMACS code. The researchers then used this code to analyse the movements of atoms and particles in the protein. 

They simulated different compounds docking to the S-protein spike of the coronavirus to determine if any of them might prevent the spike from sticking to human cells.

Jeremy Smith, director of the UT/ORNL Center for Molecular Biophysics, stated: ‘Our results don’t mean that we have found a cure or treatment for the coronavirus. We are very hopeful, though, that our computational findings will both inform future studies and provide a framework that experimentalists will use to investigate these compounds further. Only then will we know whether any of them exhibit the characteristics needed to mitigate this virus.’

This research used resources of the Oak Ridge Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC05-00OR22725.

How does SARS-CoV-2 bind to cell membranes?

Several studies have already shown that the ‘CoV spike (S) protein to be a target of interest as it may be used to block the ability of the virus to bind with cell membranes.’ 

A recent study published in Nature Cellular & Molecular Immunology (2020) entitled: ‘Characterisation of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for the development of RBD protein as a viral attachment inhibitor and vaccine’ notes that targetting the 'S protein' is the best-known path to a vaccine as it could stop the virus binding to the ACE2 receptor. The paper, written by Tai et al states: ‘The CoV spike (S) protein plays the most important role in viral attachment, fusion and entry, and serves as a target for the development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors.’

This is not necessarily new information, as many papers over the last ten years have reported similar findings, such as this paper in 2009. However, with the growing threat of COVID-19, researchers are trying to establish everything they can about the virus and the illness that it causes. ‘The spike protein of SARS-CoV — a target for vaccine and therapeutic development’ published in 2009 Nature Reviews Microbiology volume 7, 226–236(2009) by L et al, notes that ‘SARS-CoV S protein mediates binding of the virus with its receptor angiotensin-converting enzyme 2 (ACE2) and promotes the fusion between the viral and host cell membranes and virus entry into the host cell.’

Another research paper, published in 2007, in the American Society for Microbiology, Journal of Virology notes that: ‘Based on the present study, we propose a model for SARS-CoV’s internalisation by target cells. SARS-CoV attaches the cell surface through an interaction between the envelope spike glycoprotein and its receptor, ACE2.’ 

At the present time, much of the research is focused on the interaction between SARS-CoV-2 and the ACE2 receptor. While this research does not yet have answers or a possible cure for the COVID-19 pandemic, progress will undoubtedly shed light on how to prevent the viral outbreak and other potential outbreaks.


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HPC, Modelling & simulation

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