Health
Researchers identify multiple molecules that stop the SARS-Cov-2 polymerase reaction
A library of molecules with unique structural and chemical characteristics inhibits a novel coronavirus polymerase, the major drug target of COVID-19
SARS-CoV-2, a coronavirus that causes the global COVID-19 pandemic, uses a protein called a polymerase to replicate its genome in infected human cells. Stopping the polymerase reaction stops the growth of coronavirus, leading to the eradication of the human host’s immune system.
researcher Colombian engineering The University of Wisconsin-Madison has identified a library of molecules that stop the SARS-CoV-2 polymerase reaction. This is an important step in establishing the potential for further modification of these molecules as lead compounds for the development of COVID-19 therapeutics. .. Five of these molecules are already FDA approved for use in the treatment of other viral infections such as HIV/AIDS, cytomegalovirus, hepatitis B. New research June 18, 2020, Antiviral research..
The Colombian team initially stated that the active triphosphate of the hepatitis C drug sofosbuvir and its derivatives acted as an inhibitor of SARS-CoV-2 polymerase based on molecular characterization and both hepatitis C virus replication requirements. It was inferred that it could be the coronavirus. Guided by Jin Yue Ju, Samuel Reuben Peter G. Wier Professor of Chemistry and Pharmacology, Director of Center for Genome Engineering & Biomolecular Engineering, Columbia University, Robert N. Kirchdorfer, Associate Professor of Biochemistry, Coronavirus Polymerase Research Specialist at the Institute of Molecular Virology and Biochemistry at the University of Wisconsin-Madison.
In a previous set of experiments testing the properties of the coronavirus polymerase that causes SARS, the researchers found that sofosbuvir triphosphate could terminate the viral polymerase reaction. Second, sofosbuvir and four other nucleotide analogs, the HIV inhibitors alovudine, zidovudine, tenofovir alafenamide, and the active triphosphate form of emtricitabine, also inhibited SARS-CoV-2 polymerase with different levels of efficiency. I showed that.
Using the molecular insights gained in these studies, the team identified 11 nucleotide analogues with varying structural and chemical characteristics as potential inhibitors of the SARS-CoV and SARS-CoV-2 polymerases. We devised a strategy to select molecules. All 11 molecules tested showed uptake, but 6 showed immediate stop of the polymerase reaction, 2 showed delayed stop and 3 did not stop the polymerase reaction.
Prodrug drugs of five of these nucleotide analogs (cidofovir, abacavir, valganciclovir/ganciclovir, stavudine, and entecavir) that stop the SARS-CoV-2 polymerase reaction are FDA for the treatment of other viral infections. Approved and its safety profile is well established. As future studies show the efficacy of drugs that inhibit viral replication in cell culture, candidate molecules and their modified forms can be evaluated for the development of potential COVID-19 therapies.
“In an effort to support this global emergency effort, we can use the structural and chemical characteristics of the identified molecules to correlate with their inhibitory activity against SARS-CoV-2 polymerase to guide design. We are very excited and we are synthesizing a new compound for the development of the COVID-19 therapeutic.” We are very grateful for the generous research support that has allowed us to accelerate this project. We are also grateful for the significant contributions from each member of the Joint Research Consortium.”
This researchA library of nucleotide analogs stops coronavirus polymerase-catalyzed RNA synthesis that causes SARS and COVID-19.. “ Antiviral research. August 2020.
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