Potential Of Hepatitis C Drugs To Treat COVID-19: Study
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"Currently, there are no inhibitors approved by the Food and Drug Administration that target the SARS-CoV-2 main protease," said ORNL lead author Daniel Kneller. What they found is that hepatitis C drugs bind to and inhibit the coronavirus protease. This is an important first step in determining whether these drugs should be considered as potential repurposing candidates to treat COVID-19.

The SARS-CoV-2 coronavirus spreads by expressing long chains of polyproteins that must be cut by the main protease to become functional proteins, making the protease an important drug target for researchers and drug developers.

In the study, the team looked at several well-known drug molecules for potential repurposing efforts including leupeptin, a naturally occurring protease inhibitor, and three FDA-approved hepatitis C protease inhibitors: telaprevir, narlaprevir and boceprevir.

The team performed room temperature X-ray measurements to build a three-dimensional map that revealed how the atoms were arranged and where chemical bonds formed between the protease and the drug inhibitor molecules. To better understand how well or how tightly the inhibitors bind to the protease, they used in vitro enzyme kinetics, a technique that enables researchers to study the protease and the inhibitor in a test tube to measure the inhibitor's binding affinity, or compatibility, with the protease.

Pockets within the protease where a drug molecule would attach are highly malleable, or flexible, and can either open or close to an extent depending on the size of the drug molecules.

"You can't design a drug without knowing how it works on a molecular level, and the data we're providing is exactly what developers need to design stronger, more tightly binding drugs for more effective treatments." said ORNL corresponding author Leighton Coates. The X-ray measurements and synthesis of the protease samples used in the experiments were performed with support from the Center for Structural and Molecular Biology using facilities located at the Spallation Neutron Source.

Source:
https://www.cell.com/structure/fulltext/S0969-2126(20)30379-8?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S0969212620303798?showall=true#
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