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AT-527 enters clinical trials for COVID-19 treatment

AT-527 is a nucleoside analogue that is being developed as a potential treatment for COVID-19. The drug is taken orally. This drug is an analogue of a naturally occurring substance called guanosine. In cells, guanosine is used to make RNA and DNA.

Experiments with cells in the lab have found that AT-527 has potent antiviral activity against SARS-CoV-2. The drug works by interfering with an enzyme needed by the virus called RNA polymerase. This enzyme is also used by other coronaviruses and potentially AT-527 could be used against them as well.

Experiments in monkeys and people have found that AT-527 is well absorbed and, according to the developer, Atea Pharmaceuticals, “well tolerated.” When taken at a dose of 550 mg twice daily, levels of AT-527 in the lungs are high.

AT-527 is currently in a clinical trial with people diagnosed with COVID-19. Preliminary findings from a study of 30 people suggest that the drug is safe. The drug’s impact on the course of COVID-19 will hopefully be known in the months ahead.

—Sean R. Hosein

REFERENCES:

  1. Zhou XJ, Horga A, Morelli G, et al. High lung levels of active triphosphate predicted with oral AT-527 in COVID-19 patients. In: Program and abstracts of the Conference on Retroviruses and Opportunistic Infections, 6–10 March 2021. Abstract 364.
  2. Good SS, Moussa A, Zhou XJ, et al. Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus. PLoS One. 2020 Jan 8;15(1):e0227104.
  3. Berliba E, Bogus M, Vanhoutte F, et al. Safety, pharmacokinetics and antiviral activity of AT-527, a novel purine nucleotide prodrug, in HCV-infected subjects with and without cirrhosis. Antimicrobial Agents and Chemotherapy. 2019 Sep 30;63(12):e01201-19.
  4. Good SS, Westover J, Jung KH, et al. AT-527, a double prodrug of a guanosine nucleotide analog, is a potent inhibitor of SARS-CoV-2 in vitro and a promising oral antiviral for treatment of COVID-19. Antimicrobial Agents and Chemotherapy. 2021 Mar 18;65(4):e02479-20.