Qs people asked me on science and my replies to them - Part 184

Krishna: I have answered several of these questions in recent times not only here but at several other places. These questions show how science and scientists aroused people’s expectations. And the frustrations people also face because of their impatience.

However, let me also tell you no matter how much you taunt scientists ( using words like ‘big’, ‘around the world’), science can’t be rushed through.

Okay, now let me tell you why you can’t have what you want.

There are a few reasons for this.

1. Science is an extremely slow process unlike other areas of human understanding which don’t need validity to accept.

2. This is a new disease ( with a lot of unknowns) of global proportions. Huge problem needs colossal effort to understand. This rapid spread has presented health experts with a rapidly evolving and complex challenge.

3. There are several areas to study and understand like many of the features of coronavirus biology ( understanding of their capacity for adaptation to new environments, transspecies infection, and emergence of various symptoms), pathogenesis ( intracellular replication and viral cell biology, transpecies adaptation), disease manifestation, human immune response, drugs, vaccines, preventive measures.

4. Complexity of human genetics related immune responses and treatments.

5. This virus is highly contagious and deadly needing special labs to work in and equipment to deal with it.

5. Viruses are not living beings. Outside a host, viruses are dormant. They have none of the traditional trappings of life: metabolism, motion, the ability to reproduce. A virus is being somewhere “between chemistry and biology.”

Viruses function through us. With no cellular machinery of their own, they become intertwined with ours. Their proteins are our proteins. Their weaknesses are our weaknesses. Most drugs that might hurt them would hurt us, too.

For this reason, antiviral drugs must be extremely targeted and specific. They tend to target proteins produced by the virus (using our cellular machinery) as part of its replication process. These proteins are unique to their viruses. This means the drugs that fight one disease generally don’t work across multiple ones.

6. Co-infections. Other opportunistic microbes creating complex situations making things more difficult.

7. Viruses ability to mutate. Because viruses evolve so quickly, the few treatments scientists do manage to develop don’t always work for long. This is why scientists must constantly develop new drugs to treat viral diseases, and why patients take a “cocktail” of antivirals that viruses must mutate multiple times to resist.

Most medicines take at least 20–30 years to come into existence. It is that difficult.

Developing new drugs takes a very long time and costs a great deal of money. There are three stages to this process:

• Discovery: Identifying new compounds that help treat disease
• Development: Administering the new drug to animals and humans to make sure it is safe and effective
• Manufacturing: Producing the new drug in large quantities for distribution

Creating new medicines requires a large team of scientists with training in many different scientific disciplines including various areas of chemistry, biology, engineering, informatics and medicine.

Pharmaceutical Scientist | explorehealthcareers.org

Urgency should not be used as an excuse for lowering scientific standards. And we don’t!

Do you think any of these things are easy to study and comprehend despite years of training?

8. There are so many problems and so few experts. Do you know many scientists are not even sleeping for several days?

9. Science communication problems. Media interpretations are highly confusing than actual problem.

10. Paucity of funds. Funding for research on coronaviruses increased after the SARS outbreak, but in recent years that funding has dried up. The resultant lack of proper equipment and resources. For years scientific research has been neglected and sidelined. Scientists have to grapple with what little they have.

Scientists are saying that ‘they can Stop the Next Pandemic Before It Starts’. ‘Just give us funds’ is all that they are asking.

How Scientists Could Stop the Next Pandemic Before It Starts

Now give them funds before complaining. Or bring pressure on your governments to do that.

11. Politics and the games the leaders play with science.

12. Non-cooperative public spreading misinformation like wild fire.

I can go on and on like this.

Scientists are fighting wars on several fronts without proper weapons, in unfavourable conditions and with unknown and unpredictable enemy.

Try to understand and don’t criticize them. Have patience. If anybody can help the world now, it is only the scientific community. Trust them and let them do their work. They won’t disappoint you.

Q: What are the best methods according to scientists to tackle COVID19?

Krishna: Over 1,650 articles on COVID-19 are already listed in databases such as Google Scholar, while dozens more are added daily. The register ClinicalTrials.gov lists over 460 ongoing clinical trials on COVID-19, although the majority are still in the earliest stages.

When some researchers reviewed (1) these papers, they found some very useful. 

In a new study in Frontiers in Microbiology, aimed at the research community but also comprehensible for non-specialists, experts from the University of North Carolina at Chapel Hill review possible strategies against dangerous coronaviruses—not only SARS-CoV-2 and its relatives such as SARS-Cov (causing Severe Acute Respiratory Syndrome, SARS) and MERS-Cov (causing Middle East Respiratory Syndrome, MERS), but also as yet unknown strains which will inevitably emerge in the future.

They propose that the most promising approaches for fast progress are selected antivirals such as remdesivir, and gene therapy.

The authors discuss one-by-one the possible strategies against the coronavirus. First, and most effective are vaccines.

In the present case, the most successful are likely to carry the Receptor Binding Domain (of the virus's S-protein), which allows it to bind to and fuse with host cells. Besides the traditional live attenuated, inactivated, and subunit-based vaccines, modern types such as DNA/RNA-based and nanoparticle- or viral vector-borne vaccines should be considered.

Because the amino acid sequence of the S-protein is very different across coronaviruses (e.g., 76-78% similarity between SARS-Cov and SARS-Cov-2), vaccines against one strain typically won't work against another.

But because the development and testing of new vaccines takes one to several years, other approaches are essential in the meantime.

The second-most likely effective are broad-spectrum antivirals such as nucleoside analogs, which mimic the bases in the virus's RNA genome and get mistakenly incorporated into nascent RNA chains, stalling the copy process.

But because coronaviruses have a so-called "proofreading" enzyme which can cut such mismatches out, most nucleoside analogs don't work well. Exceptions seem to be β-D-N4-hydroxycytidine and remdesivir, proposed by the authors as good candidates against SARS-Cov-2.

Third, convalescent blood plasma from patients who recovered, with low levels of a range of antibodies against the virus; or preferably (but slower to develop), monoclonal antibodies, isolated and mass-produced through biotechnology. Such "passive immunization" can give short-term immunity.

The authors discuss a range of options from fusion inhibitors, to inhibitors of human proteases, to immune modulators such as corticosteroid hormones, and others.

Finally, and in the authors' view the most attractive alternative until a vaccine is produced, is gene therapy delivered through the adeno-associated virus (AAV). This would entail the fast, targeted delivery of antibodies, immunoadhesins, antiviral peptides, and immunomodulators to the upper airways, to give short-term protection. Because the rapid turnover of cells here, risks of toxicity are minimal. They estimate that such tools can be developed, adapted, and tested within a month.

AAV-based passive immunization can be used as a quick alternative. It is straightforward and only contains two components, the viral vector and the antibody. Multiple AAV vectors have been proven to be safe and effective for human use.

In theory, a single dose could mount a protective response within a week and last for more than a year. The currently high price could be reduced when treating infectious diseases, which have a larger market. It may or may not already be too late to use AAV to treat SARS-CoV-2, but it is certainly not too late for future outbreaks.

Q: Can you give what symptoms can we expect because of COVID19 infection? What other health consequences can we face after recovery?

Krishna: First thing most people notice is  loss of their sense of smell and taste. 

Later, respiratory infection that causes fever, aches, tiredness, sore throat, cough and, in more severe cases, shortness of breath and respiratory distress occurs.

We now understand that COVID-19 can also infect cells outside of the respiratory tract and cause a wide range of symptoms from gastrointestinal disease (diarrhoea and nausea) to heart damage ( Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias) and blood clotting disorders.

It now appears that we have to add neurological symptoms to this list, too.

Several recent studies have identified the presence of neurological symptoms in COVID-19 cases. Some of these studies are case reports where symptoms are observed in individuals. Several reports have described COVID-19 patients suffering from Guillain–Barré syndrome. Guillain–Barré syndrome is a neurological disorder where the immune system responds to an infection and ends up mistakenly attacking nerve cells, resulting in muscle weakness and eventually paralysis.

Other cases studies have described severe COVID-19 encephalitis (brain inflammation and swelling) and stroke in healthy young people with otherwise mild COVID-19 symptoms.

These studies have shown that 36% of patients have neurological symptoms. Many of these symptoms were mild and include things like headache or dizziness that could be caused by a robust immune response. Other more specific and severe symptoms were also seen and include loss of smell or taste, muscle weakness, stroke, seizure and hallucinations.

Changes in consciousness, such as disorientation, inattention and movement disorders, were also seen in severe cases and found to persist after recovery.

SARS-CoV-2, the coronavirus that causes COVID-19, may cause neurological disorders by directly infecting the brain or as a result of the strong activation of the immune system.

Recent studies have found the novel coronavirus in the brains of fatal cases of COVID-19. It has also been suggested that infection of olfactory neurons in the nose may enable the virus to spread from the respiratory tract to the brain.

Cells in the human brain express the ACE2 protein on their surface. ACE2 is a protein involved in blood pressure regulation and is the receptor the virus uses to enter and infect cells. ACE2 is also found on endothelial cells that line blood vessels. Infection of endothelial cells may allow the virus to pass from the respiratory tract to the blood and then across the blood-brain barrier into the brain. Once in the brain, replication of the virus may cause neurological disorders.

SARS-CoV-2 infection also results in a very strong response by the immune system. This immune response may directly cause neurological disorders in the form of Guillain–Barré syndrome. But brain inflammation might also indirectly cause neurological damage, such as through brain swelling. And it’s associated with – though doesn’t necessarily cause – neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

Q: The novel corona virus is mutating. Will it become more virulent?

 https://www.medrxiv.org/content/10.1101/2020.04.14.20060160v1.full....

Q: Why do trees lean? 

Krishna: The usual answer : A tree  leans because it has grown towards the sun often has a curving trunk. The trunk curves because of the tree's ability to adapt over time to the changing availability of sunlight. Its root system will grow to accommodate the “off center” weight distribution, up to a point.

The higher concentration of auxin on the shady side causes the plant cells on that side to grow more so it bends toward the light. ... This bending toward light is called phototropism. Phototrophism is a response that causes house plants to lean towards the window and trees to branch over the road.

Image source: https://www.budgetdumpster.com/

However, there are several other reasons too as to why a tree might lean .  Normally, it is a combination of some/all of the points below:

• Weight distribution: Depending on the diameter of the trunk and especially the height of a tree, gravity can create problems. So the main question is how the weight of the crown is distributed over the tree's trunk.
• Species variability: Different species of trees have different root systems, some go deeper and others don't. The depth and width of the root system are factors to consider when assessing a leaning tree.
• Environmental factors: There are a variety of environmental factors that will contribute to a tree leaning. For example, a tree that leans because it has grown towards the sun often has a curved trunk. The trunk curves due to the tree's ability to adapt over time to the changing availability of sunlight. Its root system will grow to accommodate the “off center” weight distribution, up to a point. Additionally, storms or constant wind can obviously cause a tree to lean.
• Structural damage: Leaning trees that don’t have a “sweep” (caused by wind) but tend to have a fairly straight trunk generally have a history of structural damage to the root system or storm damage that has caused the root system to slip, break, sink or simply fail to support the tree in some fashion. If the trunk appears to enter the ground without a mound of soil on the side away from the lean, then the root system has sunk, either from rot, mechanical fracture, physical cutting of the root plate or soil subsidence. If the mound does exist on the back side of the lean, that's a sign that the root plate is being tipped out of the ground and the roots have failed - either through mechanical wounding or structural failure. As roots break under stress from wind or off center crown weight pushing the trunk away from the soil holding the roots, the up-wind side of the root plate will tip out of the ground.

In addition, it may be worth mentioning that time plays an important role here too. Older trees will have been exposed to the forces of nature and plant pathogens for longer than younger ones so it certainly makes sense to take the life cycle of a tree into consideration, some live longer than others and thus may have been subject to wind while the other surrounding trees weren't "tall" enough to shield off any of the wind etc.

Sources: Georgia Forestry Commission - Leaning Trees - What's up with that

Citations:

1. Longping V. Tse et al, The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses, Frontiers in Microbiology (2020). DOI: 10.3389/fmicb.2020.00658