Galidesivir Explained

Galidesivir (BCX4430, immucillin-A) is an antiviral drug, an adenosine analog^[1] (a type of nucleoside analog).^[2] It was developed by BioCryst Pharmaceuticals with funding from NIAID, originally intended as a treatment for hepatitis C, but subsequently developed as a potential treatment for deadly filovirus infections such as Ebola virus disease and Marburg virus disease, as well as Zika virus.^[3] Currently, galidesivir is under phase 1 human trial in Brazil for coronavirus.

It also shows broad-spectrum antiviral effectiveness against a range of other RNA virus families, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses, flaviviruses, and phleboviruses.^[4] Galidesivir has been demonstrated to protect against both Ebola and Marburg viruses in both rodents and monkeys, even when administered up to 48 hours after infection,^[1] and development for use in humans was then being fast-tracked due to concerns about the lack of treatment options for the 2013-2016 Ebola virus epidemic in West Africa.^[5]

Galidesivir later showed efficacy against Zika virus in a mouse model.^[6]

Galidesivir abrogates viremia in Zika virus–infected rhesus Macaques.^[7]

Galidesivir is one of several antiviral drugs being tested for coronavirus disease 2019.^[8]

On April 9, 2020, BioCryst opened enrollment into a randomized, double-blind, placebo-controlled clinical trial to assess the safety, clinical impact and antiviral effects of galidesivir in patients with COVID-19.

Notes and References

1. Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Van Tongeren SA, Dong L, Retterer CJ, Eaton BP, Pegoraro G, Honnold S, Bantia S, Kotian P, Chen X, Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S . 6 . Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430 . Nature . 508 . 7496 . 402–405 . April 2014 . 24590073 . 7095208 . 10.1038/nature13027 . 2014Natur.508..402W .
2. Kamat SS, Burgos ES, Raushel FM . Potent inhibition of the C-P lyase nucleosidase PhnI by Immucillin-A triphosphate . Biochemistry . 52 . 42 . 7366–7368 . October 2013 . 24111876 . 3838859 . 10.1021/bi4013287 .
3. Galidesivir Stops Zika Viral Replication in Primate Model. BioCryst Pharmaceuticals, Inc. . June 10, 2020. GlobeNewswire News Room.
4. Westover JB, Mathis A, Taylor R, Wandersee L, Bailey KW, Sefing EJ, Hickerson BT, Jung KH, Sheridan WP, Gowen BB . 6 . Galidesivir limits Rift Valley fever virus infection and disease in Syrian golden hamsters . Antiviral Research . 156 . 38–45 . August 2018 . 29864447 . 6035881 . 10.1016/j.antiviral.2018.05.013 .
5. Web site: BioWar Lab Helping To Develop Treatment For Ebola . Rodgers P . Forbes Magazine . 8 April 2014 .
6. Julander JG, Siddharthan V, Evans J, Taylor R, Tolbert K, Apuli C, Stewart J, Collins P, Gebre M, Neilson S, Van Wettere A, Lee YM, Sheridan WP, Morrey JD, Babu YS . 6 . Efficacy of the broad-spectrum antiviral compound BCX4430 against Zika virus in cell culture and in a mouse model . Antiviral Research . 137 . 14–22 . January 2017 . 27838352 . 5215849 . 10.1016/j.antiviral.2016.11.003 .
7. Lim SY, Osuna CE, Best K, Taylor R, Chen E, Yoon G, Kublin JL, Schalk D, Schultz-Darken N, Capuano S, Safronetz D, Luo M, MacLennan S, Mathis A, Babu YS, Sheridan WP, Perelson AS, Whitney JB . 6 . A direct-acting antiviral drug abrogates viremia in Zika virus-infected rhesus macaques . Science Translational Medicine . 12 . 547 . June 2020 . 32522808 . 7370316 . 10.1126/scitranslmed.aau9135 .
8. Web site: Duddu P . Coronavirus outbreak: Vaccines/drugs in the pipeline for Covid-19 . clinicaltrialsarena.com . 19 February 2020 . 19 February 2020 . 19 February 2020 . https://web.archive.org/web/20200219184512/https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/ . dead .