An arsenal of potential treatments takes aim at proteins that are key to the virus’ life cycle.  In March 2020, as the full scope of the COVID-19 pandemic was coming into view, Jen Nwankwo and colleagues turned a pair of artificial intelligence (AI) tools against SARS-CoV-2. One newly developed AI program, called SUEDE, digitally screens all known drug-like compounds for likely activity against biomolecules thought to be involved in the disease. The other, BAGEL, predicts how to build inhibitors to known targets. The two programs searched for compounds able to block human enzymes that play essential roles in enabling the virus to infect its host cells. While SUEDE sifted through 14 billion compounds in just a few hours and spat out a hit, BAGEL created equally fast new leads.

 

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The COVID-19 vaccine may spell the end of the pandemic, but while mass vaccination is not available it is vital to stop community transmission. The new antiviral drug MK-4482 / EIDD-2801 or Molnupiravir, has managed to suppress “completely” the transmission of the coronavirus in just 24 hours , according to studies by the Institute of Biomedical Sciences of Georgia State University.  “This is the first demonstration of an orally available drug that quickly blocks the transmission of SARS-CoV-2 , so it could be a game changer,” the researchers explained in the work published in the journal Nature Microbiology .  The antiviral drug was developed at Emory University in Atlanta by the drug innovation company Drug Innovation Ventures at Emory (DRIVE), which was licensed by Ridgeback Biotherapeutics, which partnered with Merck & Co. Molnupiravir was originally designed to treat the flu and prevent the virus from making copies of itself, creating errors during viral RNA replication.

 

The experts detail that tests were carried out on ferrets and it was observed that they presented a reduction in the amount of viral particles. Then those ferrets were put with others that had not been treated. None of the ferrets in the second group became infected with COVID-19.  “We believe that ferrets are a relevant transmission model because they easily spread SARS-CoV-2, but for the most part they do not develop a serious disease, which is very similar to the spread of SARS-CoV-2 in young adults,” he said. Dr. Robert Cox, a postdoctoral fellow in the Plemper group and co-lead author of the study.  “We observed early on that MK-4482 / EIDD-2801 has broad spectrum activity against respiratory RNA viruses and that oral treatment of infected animals with the drug reduces the amount of viral particles spread by several orders of magnitude, drastically reducing transmission. These properties made MK-4482 / EIDD / 2801 a powerful candidate for the pharmacological control of Covid-19 ”, the report adds.

 

If this ferret-based data is translated into humans, Covid-19 patients treated with the drug could become non-infectious within 24 hours of starting treatment. The drug can be taken orally, and treatment can be started early for a triple potential benefit: inhibiting patients’ progress to severe disease, shortening the infectious phase to alleviate the emotional and socioeconomic cost of prolonged patient isolation, and containing quickly local outbreaks. Molnupiravir is currently in advanced phase II / III clinical trials. It is being tested in three different doses every 12 hours for five days in patients with SARS-CoV-2.

 

Findings published in Nat. Microbiology (Dec. 3, 2020):

https://doi.org/10.1038/s41564-020-00835-2

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