In this and the posts to follow, we will introduce project GRFT, what this project is doing, and why it's important. GRFT = Griffithsin. The first part of our story starts here.
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Seaweed
In the
1800’s a widow, Mrs. Amelia Griffiths (1768-1858), roamed the seacoasts of
Devon, Cornwall and Dorset with her wicker basket in hand, passionately collecting
and cataloging the marine algae commonly known as seaweed. In honor of Mrs. Griffiths and her
contributions to the science of phycology, the Swedish marine botanist Carl Adolph
Agardh named a genus of red marine algae “Griffithsia”.
Griffithsia setacea from
Griffiths’ books. © 2014 Royal Albert Memorial Museum & Art Gallery, Exeter
City Council
Griffithsia
are eukaryotic organisms of the Rhodophylum (Rhodo, from the ancient Greek,
Rhodon, Rose and phylum which in the taxonomy stack is below kingdom and above
class). Griffithsia are found in the oceans of the world. They dance gracefully in
Neptune’s realm off the Coast of New Zealand.
Viruses
In the late
1800’s, tobacco plantations in the Ukraine and Bessarabia (now Moldova) were,
like many other plantations worldwide, infected with a disease that caused
spots on the leaves causing a mottled appearance or mosaic pattern. This was called mosaic disease because the
patterns sometimes resembled mosaics.
The disease could and did destroy entire tobacco crops. Scientists in Russia and Europe started an
inquiry into the cause of the disease.
Was it a mold or a bacteria? Was
it something else? Conducting
experiments, they found that the agent which infected the plants passed through
filters with a small pore size that would have stopped bacterial cells. It could not be seen with the microscopes in
use at the time. It would not grow on
prepared media on which bacteria or fungi would thrive. So this was something as yet undiscovered. Dmitry I. Ivanovsky and Martinus W. Beijerinck
started the groundwork for what would become Virology, the study of viruses.
What is a
virus? First we should look at what a
virus is not. Animal, vegetable, or
mineral it is not. Fungus or bacteria it
is not. Viruses can't be considered
cells or independently living organisms. Perhaps viruses are best imagined as
being exquisite alien machines running a program to inject nucleotides into living cells causing the cellular mechanism
to produce more of the virus. Viruses
are made of nucleotides often dressed up in a protein coat or capsid.
Not all
viruses cause health problems. Some we
find useful for a wide variety of applications including Biomanufacturing by
the expression of of recombinant protein in organisms. Viruses considered pathogenic to humans only
number about 100 - 200 varieties. These disease causing viruses, however,
represent a major health concern and are a significant cause of mortality and
suffering worldwide.
Prevention of viral outbreaks
Prevention
of the spread of pathogenic viruses may be accomplished in several ways, for
example:
1.
Physical
distancing, physical barriers.
These
keep the virus particles, known as virions, away from cells by methods such as
masking and wearing other PPE, also by air filtration.
2. Vaccines
Vaccination
stimulates the immune response with the body producing antibodies against the
particular virus. Vaccination usually
only requires 1-3 doses of the vaccine and may provide immunization for a
lifetime.
Antivirals
Antivirals
prevent the virus from hijacking cells in the host and replicating. The antiviral works typically by blocking
entry into the cell by the virus.
Antivirals need to be taken whenever there is danger of the transmission
of a virus. Antivirals generally work
against pathogenic viruses when administered before or at the first stages of
infection.
Antiviral lectins
A lectin
may be defined as a carbohydrate binding protein.
Lectins are
found in everywhere in nature including in the food we eat.
An example
of an antiviral lectin is BanLec or banana lectin. Found in the bananas Musa acuminata and Musa balbisiana, BanLec has been shown to be effective
against HIV.
Other
examples of effective antiviral lectins found in nature are cyanovirin-N,
scytovirin, and microvirin.
Griffithsin
Of all the known antiviral lectins
found in nature, perhaps griffithsin, the red seaweed protein, is the shining
star. Besides being free of significant toxicity, griffithsin is the most
powerful of any of the lectins at inhibiting enveloped viruses from entering
cells.
Griffithsin,
or GRFT is a 121 amino acid, 12.7 kDa protein.
Wild type
GRFT:
Please take
a look at position 31 above. In wild
GRFT, this is a non-standard amino acid and in recombinant GRFT this is
generally replaced by substituting alanine (the red A).
The yellow
arrows designate the secondary B-sheet structures of the protein.
GRFT is a
dimer and has 3 triangular prismatic blades in the Beta sheets. These separately have been shown to have some
antiviral properties, however together in griffithsin’s domain swapped dimer they
are more powerful, just as two hands can grab and hold with more strength than
one hand. This dimeric structure has six
carbohydrate binding sites that work together.
An
interactive 3D model of the GRFT protein structure may be found here, scroll down to "Structure" and play with it.
Future episodes to follow!
