DRACO

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DRACO ( double-stranded RNA activated caspase oligomerizer ) is a group of experimental antiviral drugs formerly under development at the Massachusetts Institute of Technology. In cell culture, DRACO was reported to have broad-spectrum efficacy against many infectious viruses, including dengue flavivirus, Amapari and Tacaribe arenavirus, Guama bunyavirus, H1N1 influenza and rhinovirus, and was additionally found effective against influenza in vivo in weanling mice. [1] It was reported to induce rapid apoptosis selectively in virus-infected mammalian cells, while leaving uninfected cells unharmed. [1]

Contents

As of January 2014, work had moved to Draper Laboratory for further testing and development; "the team looks forward to larger scale animal trials and clinical human trials within a decade or less". [2] Dr. Todd Rider presented at the SENS Foundation's SENS6 conference. [3] He left the Draper Laboratory in May 2015 and started a crowdfunding campaign at Indiegogo to raise funds to test the drugs against the herpesvirus and retrovirus families. [4] In total it was predicted that $500,000 per year for 4 years would be needed to optimise and demonstrate DRACOs against clinically relevant viruses, [5] however, two crowdfunding campaigns for $90,000 both failed to reach their target in 2016.

In 2015, an independent research group reported to have successfully observed antiviral activity against the porcine reproductive and respiratory syndrome virus (PRRSV) using DRACOs in vitro. [6]

As of December 2015, research related to DRACOs had ground to a halt due to a lack of funding. [7]

In July 2020, a paper from another independent research group about the effects of DRACO in vitro was published. According to the study, DRACO was nontoxic in uninfected mammalian cells, and cells infected with H1N1 influenza virus showed a "significant", dose-dependent level of apoptosis. [8]

In August 2020 a company called Kimer Med in New Zealand started developing VTose, a derivative of DRACO. [9]

In June 2023 Kimer Med reported that it had "achieved two 100% positive results in tests against the priority viruses Dengue (DENV-2) and Zika (ZIKV). The tests were carried out by an independent laboratory in the United States, where Kimer Med’s antiviral compound, VTose, demonstrated 100% effectiveness against both Dengue and Zika virus in viral cytopathic effect (CPE) reduction assays, with low toxicity."

The same article reported that Kimer Med’s antiviral VTose compounds have now shown efficacy against a total of seven different viruses.

In March 2024 Kimer Med announced it has signed a contract valued at up to USD$750,000 (NZD$1.3 million) with Battelle Memorial Institute (Battelle), the world’s largest independent, nonprofit research and development organisation. The contract is focused on the discovery and development of new antiviral drug candidates for the treatment of alphaviruses.

The same article reported that since it launched in 2020, "Kimer Med has since developed innovative antivirals that have shown efficacy against 11 different viruses, including Dengue (all four types), Zika virus, and Herpes Simplex-2 (HSV-2)."

Introduction

There are very few therapies or prophylactics for serious viruses, but for the ones that do exist, they can be divided into 3 categories:

  1. Special inhibitors of a virus-associated target (e.g. HIV protease inhibitors, RNAi) [1]
  2. Vaccines, but vaccines require modification for each new virus or viral strain.
  3. Interferons, but they are less virus specific and are only receptive to certain viruses.

So in order to overcome these obstacles the antiviral DRACO was developed.

Mechanism

DRACO is selective for virus-infected cells. Differentiation between infected and healthy cells is made primarily via the length and type of RNA transcription helices present within the cell. Most viruses produce long dsRNA helices during transcription and replication. In contrast, uninfected mammalian cells generally produce dsRNA helices of fewer than 24 base pairs during transcription. Cell death is effected via one of the last steps in the apoptosis pathway in which complexes containing intracellular apoptosis signalling molecules simultaneously bind multiple procaspases. The procaspases transactivate via cleavage, activate additional caspases in the cascade, and cleave a variety of cellular proteins, thereby killing the cell. [1]

It has been shown that DRACOs are nontoxic in 11 mammalian cells types and effective against 15 different viruses. [1]

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References

  1. 1 2 3 4 5 Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, Zusman BD (2011). "Broad-spectrum antiviral therapeutics". PLoS ONE . 6 (7): e22572. Bibcode:2011PLoSO...622572R. doi: 10.1371/journal.pone.0022572 . PMC   3144912 . PMID   21818340.
  2. ↑ "Todd Rider Joins Draper to Continue Antiviral Therapeutics Development" (Press release). Cambridge, MA. PRWeb. January 8, 2014. Retrieved April 8, 2014.
  3. ↑ "PANACEA broad-spectrum antiviral therapeutics". SENS6 Proceedings. Retrieved 2014-04-11.
  4. ↑ "Dr. Todd Rider from MIT Announces IndieGoGo Campaign to Raise Funds to Test and Optimize DRACOs Against Clinically Relevant Viruses". PRWeb. Retrieved 2015-10-26.
  5. ↑ "DRACO May Be A Cure For All Viral Infections". Indiegogo. Retrieved 2019-10-31.
  6. ↑ Guo C, Chen L, Mo D, Chen Y, Liu X (March 15, 2015). "DRACO inhibits porcine reproductive and respiratory syndrome virus replication in vitro". Arch. Virol. 160 (5). State Key Laboratory of Biocontrol, Guangzhou Higher Education Mega Center, School of Life Sciences, Sun Yat-sen University, North Third Road, Guangzhou, 510006, Guangdong, People's Republic of China: 1239–47. doi:10.1007/s00705-015-2392-4. PMID   25772577. S2CID   16178322.{{cite journal}}: CS1 maint: location (link)
  7. ↑ "This man's potentially huge medical breakthrough can't get funding, so he's trying something desperate". Tech Insider. December 15, 2015.
  8. ↑ Sharti M, Esmaeili Gouvarchin Ghaleh H, Dorostkar R, Jalali Kondori B (July 28, 2020). "Double-Stranded RNA Activated Caspase Oligomerizer (DRACO): Design, Subcloning, and Antiviral Investigation". Journal of Applied Biotechnology Reports. 8 (Articles in Press). Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. doi:10.30491/jabr.2020.111083.
  9. ↑ "Our Work". Kimer Med. Retrieved 2021-01-30.
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