Latest Coronavirus Research: European Scientists Develop Broad-Spectrum Inhibitors That Eradicates Coronavirus In Vitro Studies, Animal And Human Trials Starting
Source: Coronavirus Research News Feb 27, 2020 4 years, 8 months, 2 weeks, 2 days, 1 hour, 16 minutes ago
Coronavirus Research scientists from University Of Lubeck- Germany, University of Leuven-Belgium, Leiden University-Netherlands and Shanghai Institute of Medicine-China, have in a collaborative
research developed a new broad-spectrum virus inhibitor that has so far demonstrated efficacy against a wide range of viruses in vitro studies including the new SARS-Cov-
2 coronavirus that causes the deadly Covid-19 disease.
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The team of
coronavirus researchers have designed compounds that block the replication of similar
coronaviruses, as well as other disease-causing viruses, in the lab.
However the compounds have not yet been tested in animal models or humans and the team has just only initiated two studies involving animal models.
The SARS-CoV-2 or 2019-nCoV
coronavirus , is a close relative to the severe acute respiratory syndrome (SARS) virus that caused an outbreak in 2003 (SARS-CoV-1), as well as the Middle-East respiratory disease virus (MERS-CoV) that emerged in 2012.
These
coronaviruses cause flu-like symptoms and, frequently, pneumonia. However, no effective treatments have been developed, in part because the relatively small number of cases in the past, have not warranted large expenditures by pharmaceutical companies.
Dr Hong Liu, Dr Rolf Hilgenfeld and colleagues envisioned a possible solution in the form of broad-spectrum antiviral drugs that target all
coronaviruses, as well as enteroviruses, some of which cause conditions like the common cold; hand, foot and mouth disease; and the "summer flu.
Dr Rolf Hilgenfeld from Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, told
Thailand Medical News, " All of these viruses share a similar protein-cutting enzyme, called the ‘main protease’ in
coronaviruses and the ‘3C protease’ in enteroviruses, that is essential for viral replication. By developing an inhibitor that targets these enzymes, we are able to halt replication and eradicate the viruses.”
The medical researchers examined X-ray crystal structures of the proteases and then made a series of α-ketoamide compounds that were predicted to fit snugly in the enzymes' active sites, interfering with their function. By testing the molecules in the test tube and in human cells in petri dishes, they identified one versatile inhibitor that blocked multiple
coronaviruses and enteroviruses, including SARS-CoV-1
coronavirus.
Significantly, another compound molecule showed very strong activity against MERS-CoV, with moderate activity against the other viruses. Because the main proteases of SARS-CoV-2, MERS-CoV and SARS-CoV-1 are very similar, the inhibitors will most likely show good antiviral activity against the new SARS-CoV-2
coronavirus, the researchers say. An initial lab test involving the new
coronavirus already showed success. Their next step will be to test the inhibitors in small-animal mo
dels of disease which they have already started.
They however warned even it would take months before it can be used as a standard protocol due to regulatory procedures even with fast tracking drug approval shortcuts due to the severity of the pandemic.
Reference
: Linlin Zhang et al. α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment,
Journal of Medicinal Chemistry (2020). DOI: 10.1021/acs.jmedchem.9b01828,
https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01828
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