The Scientific War against COVID-19: A Congregation of Cutting-Edge Breakthroughs and Research

Original article can be found here (source): Artificial Intelligence on Medium

Prevention

Though testing is part of the solution to prevention — in that it prevents the spread of the virus — there are other methods that we are more familiar with from dealing with previous viruses and strains, namely vaccines.

When it comes to the prevention, we have previous background knowledge to rely on as the 2019-nCoV isn’t the first pandemic that we’ve encountered even within the past century.

Traditionally, vaccines have been used to prevent future infections of the vaccines mostly by priming the immune system to fight off the virus if it gets infected in the future.

There are multiple ways in which this can be done:

  • Subunit vaccines: Also known as protein vaccines, as part of this vaccines, recombinant antigens are injected into the human body. They contain parts of the viral antigen that are weakened and unable to cause harm, but nonetheless fulfill their purpose by stimulated the human immune system.
  • mRNA vaccines: mRNA vaccines are similar in that they help the immune system recognize a particular antigen and generate immunity to it. However, in this case, the mRNA that codes for a particular antigen is inserted and the host’s own translation machinery is what allows its cells to generate the antigen and confer immunity. — Moderna therapeutics is company currently working on generating these mRNA vaccines for COVID. However, early safety tests indicate that mRNA vaccines may induce a large number of side effects in patients.

Multiple companies are working tirelessly to generate these vaccines. The main inefficiency, however, stems not from the science, but the fact that most vaccines take at least 1–3 years to be approved by the FDA and released into the market. It just turns out that this time — we don’t have that kind of time.

Small molecule drugs have also been in development and from the start, there’s been hype around a few repurposed drug — some which were previous antimalarial drugs and others which were HIV protease inhibitors. From the original pool of molecules, two seemed to have emerged triumphant:

  • Remdesivir — this small molecule is what’s known as a nucleoside analogue (a derivative of a nucleotide) that has been known to inhibit HIV protease. Gilead has launched five large clinical trials to confirm the drug’s efficacy over the next few months.
  • Chloroquine/Hydroxychloroquine — these drugs have been tested in clinical trials in China as well as other non-randomized trials and were believed to show efficacy against COVID but have not seemed to live up to their expectations based on clinical trials in China.

Right now, both of these drugs are still being used through a process known as “compassionate use,” where a new, unapproved drug can be used for severely ill patients when there are no other options available.

The good new — the World Health Organization has already started to plan a large scale global clinical trial where they’ll be testing Remdesivir and Chloroquine as well other drug cocktails involving other promising drugs such as HIV protease inhibitors Kaletra and Arbidol.

But here’s the thing — most of the approaches above are traditional and frequent ones — they’re ones we’ve used in the past for previous viruses, pandemics, and bacterial infections. And given the time-effective nature of this situation, these are likely the drugs that will be used to cure patients if they get out in time before the end of the pandemic.

Here’s some other crazy innovation that’s been going on at the intersection of COVID-19 and other technologies!

Coronavirus X Nanotech

Scientists are looking into nanoparticle-based designer vaccines for COVID-19!

Essentially, they’re using computational molecular self assembly to build a harmless nanoparticle core that would resemble the virus’s capsid and everything inside without triggering immune reactions!

On the outside of the nanoparticle core, they’re also building protein-based antigens components resembling the spike protein. However, these protein designs have to go through extensive computational simulation, as the goal is to ultimately have these proteins self assemble along with the nanoparticle core!

Once the amino acid sequences are determined, scientists look to use synthetic biology to encode the instructions to make these sequences into the DNA of E. coli. And once these proteins are then filtered and isolated, they will automatically assemble into the vaccine nanoparticles!!!

In addition to molecular self assembly component, synthetic nanoparticle protein scaffolds will enable the vaccine to be heat-resilient — in other words, the vaccine would be accessible to those in far reaching climates and altitudes.

In conjunction with manipulating DNA to code for self-assembling proteins, we’re also looking into use gene editing systems not only to teach our body not to fight these harmful viruses through the production of antigens — but also just cut the problem right at its root — literally.

Coronavirus X Gene Editing

Gene editing has been a major scientific tool on the table ever since Jennifer Doudna discovered it back in 2012. CRISPR (which stands for clustered regularly interspaced short palindromic repeats), is part of the bacterial immune system encoded into their genes. It enables them to recognize encoded viral DNA in their genomes and efficiently excise it — using a protein endonuclease called cas9 (crispr-associated protein 9).

But now — the tables have turned. We humans can the bacterial CRISPR system to edit out the harmful portions of the SARS-COV-2 genome.

However, we need a new protein player — cas13a — as cas9 can make double stranded cuts in DNA, but not RNA — and the virus that causes COVID-19 is a positive strand RNA retrovirus.

Normally, the cas complexes that snip out DNA require another nucleic acid sequence complementary to their target to guide them there — also known as gRNA.

Common intuition says that all we need to do is find an RNA sequence complementary to our given target sequences — but the task is much more complicated than it looks. Screening for what are known as “off-target effects” (essentially places where the cas13a could unintentionally excise our own DNA and cause super harmful side effects) as well as folding the gRNA into a 3-dimensional structure to assess its structural biochemistry and any unforeseen interactions it may have with surrounding macromolecules takes computational energy and time.

Fortunately, researchers have just come out with a machine learning algorithm that can propose viable gRNA sequences for complementary targets int he SARS-COV-2 genome. This could mean that RNA editing might be an alternative to other traditional vaccines and therapies.

Some other quick innovations being released by companies include

  • RNAi done through the means of siRNAs and miRNAs (aka small interfering RNAs and microRNAs respectively) are being investigated as another vaccine/potential cure. Small interfering RNAs along with microRNAs essentially bind to complementary mRNA sequences and tag them for degradation so that their harmful protein products cannot be expressed in our host cells.
  • Another really cool innovation is self replicating RNA viral vectors. This approach is being pursued by Arcturus therapeutics, and they’re combining their unique RNA approach with a nanoparticle delivery system. The benefit with self-replicating RNA is that it would require smaller doses to produce the same amount of mRNA that a traditional mRNA vaccine would provide to the host cells. Lower dosage most likely means lower toxicity.

Ultimately, though, it’s important noting that for most of these theorized and hypothesized treatments — though they’re being developed for the sole reason that they would be more efficacious than other treatments — are still in preclinical stages, and it’s highly unlikely that they’ll pass through FDA approval within a few months, or even before the pandemic subsides.

Nevertheless, as I mentioned at the beginning of the article, something amazing can be said about this specific point in history. Though COVID is presenting us with numerous challenges and obstacles through which we must stay resilient, it’s also showing us our potential as humanity to pursue to rapid scientific innovation in times of crisis.

Here’s the exponential explosion in the number of coronavirus-related publications — and this only encapsulates publications till the end of February.

Aside from all of this, we must practice social distancing as a community, wash our hands, and do our duty to prevent the spread of the virus. But it is worth acknowledging and comforting to note that some optimism, opportunity, and growth can and will emerge from the virus and these hard times.

Remember the quote from the very beginning of the article?

“The old world is dying, and the new world struggles to be born. In the twilight rise the monsters.”

Let’s see what that new world looks like.