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Corona: The Viral Phenomenon

It is impossible to exist without at least mentioning the SARS-CoV-2 that has been dominating the world these past few months.

The virus that causes COVID-19, SARS-CoV-2 (Severe Acute Respiratory Syndrome – CoronaVirus-2), turned our life upside down in March and April as it has been spreading across the world like wildfire. Going from the “New Chinese Virus” phase (something that was happening far away from Europe, in China) to engulfing the whole world and keeping us sleepless at night was such fast development, that health authorities and governments are struggling to keep up.

To try and help the factual news world, we decided to write something about it ourselves, so here’s a brief review on the matter. For exact information, we recommend you check and consult with the World Health Organisation but we can at least provide some fact-checked information on what’s going on.

About the Coronavirus

This “novel” (the quotation marks are needed as I feel the virus has been thoroughly presented and is at this point well known to us all, therefore it is not in any way novel anymore – if we continue to call it novel, it might seem as though there is an even newer virus rampaging about which is definitely not the case) coronavirus is a virus from the Coronaviridae virus family. This family also includes other known viruses that cause diseases such as the symptoms of what we all call the common cold, SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).

Coronavirus structure under the microscope.
A coronavirus under an electron microscope. A signature attribute of coronaviruses are the spike proteins, seen here as the spikes pointing outward from the membranes (Image by Nirav Soni, published on Researchgate)

The coronavirus (SARS-CoV-2) we are currently occupied with is a large and enveloped, single-stranded RNA. Its genome consists of less than 30 000 bases (for comparison: the Ebola virus consists of 19k bases, HIV of 10k bases). Some of these bases make up genes encoding more than a few proteins, which help the virus function and proliferate. Up till now, as many as 29 of these proteins have been identified – some of them serve in the process of making copies of the Coronavirus, the others in suppressing the host’s immune system (just to name a couple of functions).

The lifecycle of coronaviruses goes a little something like this:

Coronavirus lifecycle explained.
The lifecycle of a coronavirus in a simplified infographic (Image by Julian Pampel)
  1. The viral RNA enters the host cell either via endosomes or membrane fusion between the viral and host cell membranes
  2. The viral replication machinery is translated 
  3. The viral RNA is replicated
  4. The viral structure proteins are translated
  5. The viral proteins form the virion (a complete virus particle that is the extracellular infectious form of a virus) 
  6. The virion is transported through the Golgi apparatus to the host cell surface and released through exocytosis
  7. The new virions search for another host cell and the cycle repeats

Corona vs Humanity

Drug and vaccine development can take 10 years or more, which is a lot at best. A number like that seems very intimidating. Fortunately for us, thanks to the advancements we’ve already made for similar corona- and other viruses, this time can be shortened to about a year and a half, most experts believe! Some pharma and biotech companies are already trialling certain drugs and vaccines, that have been initially meant for other viruses and diseases.

At the moment there are about 300 clinical trials in progress all around the world. Here are some of the most promising companies in the back line of the Coronafight, their progress so far, and how the substance they are developing works:

Drugs

Remdesivir

First one on the list and the most promising is an anti-ebola drug by Gilead Sciences called remdesivir. As mentioned, this antiviral drug was originally developed to treat ebola and was tested in the Democratic Republic of Congo in 2018 and 2019. It showed no effect then, but in recent uses for fighting COVID-19 the positive outcomes have given remdesivir another chance.

In the U.S., for example, two cases have been reported where two patients with severe COVID-19 symptoms were given (intravenously) remdesivir and started to recover the next day. Currently there are two ongoing phase III trials in Asian countries.

Remdesivir is an inhibitor of the RNA-dependent RNA polymerase viral enzyme, used by the virus to replicate itself.

Favilavir (Favipiravir)

The first approved anti-SARS-CoV-2 drug in China is Favilavir, currently sold under the brand name Avigan. It is manufactured by the Japanese company Fujifilm Toyama Chemical.

The active pharmaceutical ingredient is called favipiravir and is also an RNA-dependent RNA polymerase inhibitor. The drug itself was manufactured and sold as an influenza virus (causing the flu) drug in Japan and China. The influenza and the coronavirus are both single-stranded RNA viruses, depending on RNA-polymerase in the replication process.

The similarity between the two viruses fueled the idea that the same drug could also be used for SARS-CoV-2. The Chinese government decided to test it for treating COVID-19 and according to medical authorities in China, favipiravir had delivered encouraging outcomes in clinical trials of 340 coronavirus-infected patients in Wuhan and Shenzhen. The patients given the drug tested negative for SARS-CoV-2 after a median of 4 days after being diagnosed with COVID-19. In comparison, the median for recovery of patients without the drug was 11 days.

Chloroquine and hydroxychloroquine

These two compounds have been quite popular lately, due to the U.S. president Donald Trump making bold claims. The truth of the matter is that evidence on chloroquine and hydroxychloroquine being effective treatments is very scarce and the medical and scientific communities agree that further testing is needed to define their potential use in the fight against COVID-19. So far things aren’t looking so great.

These drugs work by increasing acidity in endosomes. As I mentioned before, entering via endosomes is one of the ways coronaviruses get inside the host cell, however it isn’t the only nor primary way of entering. This makes it less effective, as it only prevents a smaller quantity of SARS-CoV-2 from entering the host cell. Furthemore, the compounds can also be toxic in higher doses, which can pose a serious threat to the patient.

How drugs effect replication cycle of coronavirus.
Different drugs interfere with different steps (numbers) in the virus’ replication cycle (Image by V. Altounian, Science Magazine)

Lopinavir+Ritonavir

Kaletra (the drug combo’s brand name), is a combination of lopinavir and ritonavir and is sold as a HIV drug. 

Kaletra works as a protease inhibitor in HIV’s replication cycle and that is why the thought of using it to fight the coronavirus as well arose. Some studies have shown it being effective against coronaviruses. The action of this drug is very specific to HIV though and that is one of the speculations why it hasn’t shown too much effect in the first trials.

The compound itself is a combination of drugs because lopinavir is broken down by our bodies quite quickly. Therefore a small amount of ritonavir was added to it to inhibit some of the body’s proteases. As a third helper compound interferon-beta has also been added to the duo in trials in Saudi Arabia. Interferon beta is a molecule involved in inflammation regulation in the body. 

Other drugs

Here are some other potential candidates and their manufacturers:

  • Actemra by Roche
  • Galidesivir by Biocryst Pharma
  • REGN3048-3051 and Kevzara by Regeneron
  • SNG001 by Synairgen Research
  • AmnioBoost by Lattice Biologics

Vaccines

There are six major candidates already in clinical trials. These are:

  • Adenovirus Type 5 Vector (Ad5-nCoV) by CanSino Biological Inc./Beijing Institute of Biotechnology (Phase 2)
    • Platform: non-replicating viral vector
  • ChAdOx1 by University of Oxford (Phase 2)
    • Platform: non-replicating viral vector
  • INO-4800 DNA plasmid vaccine by Inovio Pharmaceuticals (Phase 1)
    • Platform: DNA
  • Inactivated vaccine by Beijing Institute of Biological Products/Wuhan institute of Biological Products (Phase 1)
    • Platform: Inactivated
  • Inactivated vaccine by Sinovac (Phase 1)
    • Platform: inactivated
  • mRNA-1273 LNP-encapsulated mRNA by Moderna/National institute of Allergy and Infectious Diseases (NIAID)
    • Platform: RNA

Since there are many other potential vaccines for SARS-CoV-2 in the pipeline, here is a list of some of them, each one accompanied by a short description.

Corona vs The Environment

A positive aspect of this whole situation is the environmental impact. This is a popular topic among Darwinists and Global Warming activists. And it cannot be overlooked!

Even though the media likes to flash catchy headlines like “Coronavirus is good for the environment” (paraphrasing, of course), this still doesn’t mean that we have somehow magically beaten Climate Change. These articles are usually accompanied by satellite images, comparing the before and after states of emissions (NO, CO2) by a certain country.

But this, unfortunately, only sounds better than it is. Yes, the governmental restrictions and the changes in our lifestyle have drastically lowered the emissions in some more polluted areas of the world. However, these changes are far from permanent.

The current state of affairs is far more extreme than what we can expect in the following years. Once life starts to return back to normal, the emission rate will go up again and we will be heading in the same direction as before 2020 hit us. The same thing happened in many crises in the past – the pollution maps have improved for a bit and after that, they gradually returned to the ascending trend of environmental downfall.

How global CO2 emissions rise and how big crises effected this.
Global fossil CO2 emissions (in Gigatons or billions of tonnes of CO2) and carbon intensity of world Gross Domestic Product (grams of CO2 per $US 2,000), with the most important financial crises marked (Image by Global Carbon Project)

What is interesting here is that this is a different cause than it was in the past. The dips in the trend of rising emissions were caused by a financial crisis and not a pandemic. Maybe, just maybe the current changes in lifestyle will leave us a bit more conscious about the effect we have on the environment and will make us behave more responsibly in the future.  

To sum up

The SARS-CoV-2 has had a huge impact on our lives in 2020. It has affected the individual as well as the economy and is thus a formidable foe. 

We are doing our best and focusing our efforts on finding vaccines and drugs to protect ourselves against the virus. So far progress can be seen, but it’s still too early to say “yes, this thing works and is the salvation we need”. Scientists and companies are doing their best in the labs, while nurses, doctors and other healthcare professionals are fighting the pandemic on the frontlines.

COVID-19 is not good for the environment. The momentary drop of CO2 emissions will last only for as long as the factories are closed and they cannot stay closed for long, or the world will never recover from the incoming financial crisis. In the future we will have to work even harder in order to reduce our emissions and try to reverse the planet heating.

Even though most of the effects of COVID-19 are negative, there are some positive aspects to it – the emissions are dropping a bit, even if it’s just for a short period of time. This shows us that a combined effort can have changes on the health of our planet and that we should continue to work towards protecting it better.

Sources:

https://www.sciencedirect.com/science/article/pii/B9780128031094000179?via%3Dihub

https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html?fbclid=IwAR2kcH5R-QQDAdEDbnay4tzxvvzqiPB8bKkmaAW-etsy9osFGGeQaYq2EE0

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102599/

https://www.antibodies-online.com/resources/18/5410/sars-cov-2-life-cycle-stages-and-inhibition-targets/

https://theconversation.com/how-changes-brought-on-by-coronavirus-could-help-tackle-climate-change-133509

https://www.bbc.com/future/article/20200326-covid-19-the-impact-of-coronavirus-on-the-environment

https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments#

https://www.scientificamerican.com/article/heres-what-we-know-about-the-most-touted-drugs-tested-for-covid-191/

https://www.hospimedica.com/covid-19/articles/294781247/fujifilms-antiviral-becomes-first-approved-drug-to-treat-coronavirus-in-china.html

http://fftc.fujifilm.co.jp/en/avigan/?_ga=2.98121048.679860066.1587643075-1291978587.1587643075

https://www.who.int/blueprint/priority-diseases/key-action/draft-landscape-COVID-19-candidate-vaccines-23-April-2020.pdf?ua=1

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