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When you have nothing else, try burdock root

Burdock, Latin name Arctium, is a herb used in traditional Chinese medicine. We don’t rely on traditional medicine anymore, at least not as an effective tool, unless there is scientific evidence that it actually works for a specific problem.

In many countries now facing yet another viral threat, a coronavirus “born” in 2019, doctors are testing some antiviral chemicals that helped with other viruses in the past.

What are the mechanisms of action in antiviral chemicals? They vary a lot:  inactivate proteases that the virus needs to assemble or nucleoside analogs that inhibit replication of the nucleic acid that forms the core of the virus, or ribozymes that cut the virus genome, etc. Scientists study carefully the whole viral cycle and devise ways of stopping them.

But in North Korea, where science and medicine are starved and the resources are used on a nuclear weapon race, there no antivirals (or maybe there are some, for the upper echelons, just like there is food enough to fatten them). For the rest of the populace, it’s burdock.

Now, don’t get me wrong: burdock has a lot of secondary metabolites in it, like lignans, fatty acids, acetylenic compounds, phytosterols, polysaccharides, caffeoylquinic acid derivatives, flavonoids, terpenes/terpenoids and volatile compounds such as hydrocarbons, aldehydes, methoxypyrazines, carboxylic and fatty acids, monoterpenes and sesquiterpenes and. Some of them have antiviral activity, just like mint does. But I would not send you mints to protect you or help you recover, from the flu or a  COVID-19 (the coronavirus responsible from the present pandemic) outbreak. But burdock it is for North Korea, for now. Let’s hope the virus respects that particular border because it is not in viral nature to respect any border whatsoever.

In the meantime, wash your hands and pay your taxes, so that doctors, scientists and the people at the CDC can continue their work. I am not going to stock up on burdock.

These are the times when I am grateful I live in 2020 and not in 1920. Virus have always been powerful enemies of humankind but at least now we have better tools to protect us from them. A vaccine will be developed against COVID-19, just as they have been developed against other viruses, and the threat will be over, until another virus is born out of the mistakes humankind keeps making combined with nature and its powerful mechanisms,

Reference

Wang, D., Bădărau, A. S., Swamy, M. K., Shaw, S., Maggi, F., da Silva, L. E., … Atanasov, A. G. (2019). Arctium Species Secondary Metabolites Chemodiversity and Bioactivities. Frontiers in Plant Science, 10. doi:10.3389/fpls.2019.00834

 

Before cell entry

One anti-viral strategy is to interfere with the ability of a virus to infiltrate a target cell. The virus must go through a sequence of steps to do this, beginning with binding to a specific “receptor” molecule on the surface of the host cell and ending with the virus “uncoating” inside the cell and releasing its contents. Viruses that have a lipid envelope must also fuse their envelope with the target cell, or with a vesicle that transports them into the cell, before they can uncoat.

This stage of viral replication can be inhibited in two ways:

  1. Using agents which mimic the virus-associated protein (VAP) and bind to the cellular receptors. This may include VAP anti-idiotypic antibodies, natural ligands of the receptor and anti-receptor antibodies.[clarification needed]
  2. Using agents which mimic the cellular receptor and bind to the VAP. This includes anti-VAP antibodies, receptor anti-idiotypic antibodies, extraneous receptor and synthetic receptor mimics.

This strategy of designing drugs can be very expensive, and since the process of generating anti-idiotypic antibodies is partly trial and error, it can be a relatively slow process until an adequate molecule is produced.

Entry inhibitor

A very early stage of viral infection is viral entry, when the virus attaches to and enters the host cell. A number of “entry-inhibiting” or “entry-blocking” drugs are being developed to fight HIV. HIV most heavily targets the immune system’s white blood cells known as “helper T cells”, and identifies these target cells through T-cell surface receptors designated “CD4” and “CCR5“. Attempts to interfere with the binding of HIV with the CD4 receptor have failed to stop HIV from infecting helper T cells, but research continues on trying to interfere with the binding of HIV to the CCR5 receptor in hopes that it will be more effective.

HIV infects a cell through fusion with the cell membrane, which requires two different cellular molecular participants, CD4 and a chemokine receptor (differing depending on the cell type). Approaches to blocking this virus/cell fusion have shown some promise in preventing entry of the virus into a cell. At least one of these entry inhibitors—a biomimetic peptide called Enfuvirtide, or the brand name Fuzeon—has received FDA approval and has been in use for some time. Potentially, one of the benefits from the use of an effective entry-blocking or entry-inhibiting agent is that it potentially may not only prevent the spread of the virus within an infected individual but also the spread from an infected to an uninfected individual.

One possible advantage of the therapeutic approach of blocking viral entry (as opposed to the currently dominant approach of viral enzyme inhibition) is that it may prove more difficult for the virus to develop resistance to this therapy than for the virus to mutate or evolve its enzymatic protocols.

Uncoating inhibitor

Inhibitors of uncoating have also been investigated.[35][36]

Amantadine and rimantadine have been introduced to combat influenza. These agents act on penetration and uncoating.[37]

Pleconaril works against rhinoviruses, which cause the common cold, by blocking a pocket on the surface of the virus that controls the uncoating process. This pocket is similar in most strains of rhinoviruses and enteroviruses, which can cause diarrhea, meningitis, conjunctivitis, and encephalitis.

Some scientists are making the case that a vaccine against rhinoviruses, the predominant cause of the common cold, is achievable. Vaccines that combine dozens of varieties of rhinovirus at once are effective in stimulating antiviral antibodies in mice and monkeys, researchers have reported in Nature Communications in 2016.

Rhinoviruses are the most common cause of the common cold; other viruses such as respiratory syncytial virus, parainfluenza virus and adenoviruses can cause them too. Rhinoviruses also exacerbate asthma attacks. Although rhinoviruses come in many varieties, they do not drift to the same degree that influenza viruses do. A mixture of 50 inactivated rhinovirus types should be able to stimulate neutralizing antibodies against all of them to some degree.

During viral synthesis

A second approach is to target the processes that synthesize virus components after a virus invades a cell.

Reverse transcription

One way of doing this is to develop nucleotide or nucleoside analogues that look like the building blocks of RNA or DNA, but deactivate the enzymes that synthesize the RNA or DNA once the analogue is incorporated. This approach is more commonly associated with the inhibition of reverse transcriptase (RNA to DNA) than with “normal” transcriptase (DNA to RNA).

The first successful antiviral, aciclovir, is a nucleoside analogue, and is effective against herpesvirus infections. The first antiviral drug to be approved for treating HIV, zidovudine (AZT), is also a nucleoside analogue.

An improved knowledge of the action of reverse transcriptase has led to better nucleoside analogues to treat HIV infections. One of these drugs, lamivudine, has been approved to treat hepatitis B, which uses reverse transcriptase as part of its replication process. Researchers have gone further and developed inhibitors that do not look like nucleosides, but can still block reverse transcriptase.

Another target being considered for HIV antivirals include RNase H – which is a component of reverse transcriptase that splits the synthesized DNA from the original viral RNA.

Integrase

Another target is integrase, which integrate the synthesized DNA into the host cell genome.

Transcription

Once a virus genome becomes operational in a host cell, it then generates messenger RNA (mRNA) molecules that direct the synthesis of viral proteins. Production of mRNA is initiated by proteins known as transcription factors. Several antivirals are now being designed to block attachment of transcription factors to viral DNA.

Translation/antisense

Genomics has not only helped find targets for many antivirals, it has provided the basis for an entirely new type of drug, based on “antisense” molecules. These are segments of DNA or RNA that are designed as complementary molecule to critical sections of viral genomes, and the binding of these antisense segments to these target sections blocks the operation of those genomes. A phosphorothioate antisense drug named fomivirsen has been introduced, used to treat opportunistic eye infections in AIDS patients caused by cytomegalovirus, and other antisense antivirals are in development. An antisense structural type that has proven especially valuable in research is morpholino antisense.

Morpholino oligos have been used to experimentally suppress many viral types:

Translation/ribozymes

Yet another antiviral technique inspired by genomics is a set of drugs based on ribozymes, which are enzymes that will cut apart viral RNA or DNA at selected sites. In their natural course, ribozymes are used as part of the viral manufacturing sequence, but these synthetic ribozymes are designed to cut RNA and DNA at sites that will disable them.

A ribozyme antiviral to deal with hepatitis C has been suggested,[43] and ribozyme antivirals are being developed to deal with HIV.[44] An interesting variation of this idea is the use of genetically modified cells that can produce custom-tailored ribozymes. This is part of a broader effort to create genetically modified cells that can be injected into a host to attack pathogens by generating specialized proteins that block viral replication at various phases of the viral life cycle.

Protein processing and targeting

Interference with post translational modifications or with targeting of viral proteins in the cell is also possible.[45]

Protease inhibitors

Some viruses include an enzyme known as a protease that cuts viral protein chains apart so they can be assembled into their final configuration. HIV includes a protease, and so considerable research has been performed to find “protease inhibitors” to attack HIV at that phase of its life cycle.[46] Protease inhibitors became available in the 1990s and have proven effective, though they can have unusual side effects, for example causing fat to build up in unusual places.[47] Improved protease inhibitors are now in development.

Protease inhibitors have also been seen in nature. A protease inhibitor was isolated from the Shiitake mushroom (Lentinus edodes).[48] The presence of this may explain the Shiitake mushroom’s noted antiviral activity in vitro.[49]

Long dsRNA helix targeting

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. DRACO (double-stranded RNA activated caspase oligomerizer) is a group of experimental antiviral drugs initially developed 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. It was reported to induce rapid apoptosis selectively in virus-infected mammalian cells, while leaving uninfected cells unharmed. DRACO effects cell death 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.

 

 

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