Draco Modiglianii
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DRACO (
double-stranded RNA Double-stranded RNA (dsRNA) is RNA with two complementary strands found in cells. It is similar to DNA but with the replacement of thymine by uracil and the adding of one oxygen atom. Despite the structural similarities, much less is known about ...
activated
caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyste ...
oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
izer) is a group of experimental
antiviral drug Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...
s formerly under development at the
Massachusetts Institute of Technology The Massachusetts Institute of Technology (MIT) is a Private university, private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of moder ...
. In cell culture, DRACO was reported to have broad-spectrum efficacy against many infectious viruses, including dengue flavivirus, Amapari and Tacaribe
arenavirus An arenavirus is a bi- or trisegmented ambisense RNA virus that is a member of the family ''Arenaviridae''. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenavirus ...
, Guama bunyavirus, H1N1 influenza and
rhinovirus The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a Positive-sense single stranded RNA virus, positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinoviru ...
, and was additionally found effective against influenza ''in vivo'' in weanling mice. It was reported to induce rapid
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
selectively in virus-infected mammalian cells, while leaving uninfected cells unharmed. , work had moved to
Draper Laboratory Draper Laboratory is an American non-profit research and development organization, headquartered in Cambridge, Massachusetts; its official name is The Charles Stark Draper Laboratory, Inc. The laboratory specializes in the design, development, an ...
for further testing and development; "the team looks forward to larger scale animal trials and clinical human trials within a decade or less". Dr. Todd Rider presented at the
SENS Foundation The SENS Research Foundation is a non-profit organization that does research programs and public relations work for the application of regenerative medicine to aging. It was founded in 2009, located in Mountain View, California, US. The organiza ...
's SENS6 conference. He left the Draper Laboratory in May 2015 and started a
crowdfunding Crowdfunding is the practice of funding a project or venture by raising money from a large number of people, typically via the internet. Crowdfunding is a form of crowdsourcing and Alternative Finance, alternative finance, to fund projects "withou ...
campaign at
Indiegogo Indiegogo is an American crowdfunding website founded in 2008 by Danae Ringelmann, Slava Rubin, and Eric Schell. Its headquarters are in San Francisco, California. The site is one of the first sites to offer crowd funding. Indiegogo allows peo ...
to raise funds to test the drugs against the
herpesvirus ''Orthoherpesviridae'', previously named and more widely known as ''Herpesviridae'', is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are commonly known as herp ...
and
retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
families. 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, 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 Porcine reproductive and respiratory syndrome virus (PRRSV), is a virus that causes a disease of pigs, called porcine reproductive and respiratory syndrome (PRRS), also known as blue-ear pig disease (in Chinese, ''zhū láněr bìng'' 豬藍耳 ...
(PRRSV) using DRACOs ''in vitro''. , research related to DRACOs had ground to a halt due to a lack of funding. 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. In August 2020 a company called Kimer Med in New Zealand started developing VTose, a derivative of DRACO. 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 organization. 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: # Special inhibitors of a virus-associated target (e.g. HIV protease inhibitors, RNAi) # Vaccines, but vaccines require modification for each new virus or viral strain. # 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 A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
-infected
cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...
. Differentiation between infected and healthy cells is made primarily via the length and type of
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
transcription helices present within the cell. Most viruses produce long
dsRNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself ( non-coding RNA) or by forming a template for the production of proteins ( messenger RNA). RNA and deoxy ...
helices during transcription and replication. In contrast, uninfected
mammalian A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
cells generally produce dsRNA helices of fewer than 24
base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
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 Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cystei ...
. The procaspases transactivate via cleavage, activate additional caspases in the cascade, and cleave a variety of cellular proteins, thereby killing the cell. It has been shown that DRACOs are nontoxic in 11 mammalian cells types and effective against 15 different viruses.


References


External links

* * * * * * {{cite web , url=https://riderinstitute.org/ , publisher=Rider Institute , author=Rider, Todd , title=Dr Todd Rider's official website in regards to DRACO , date=October 2016 , accessdate=October 9, 2016 Anti–RNA virus drugs Massachusetts Institute of Technology