How Anti-Coronavirus Drugs May Be Produced in Plants…And Why

Novel Coronavirus SARS-CoV-2 (CC-BY-2.0) by NIAID

Remember Ebola?

About five years ago I wrote a post (please see here) about how, and why, plants were involved in developing effective therapies against the Ebola virus.

Fast-forward to the present…

…and now the human pathogenic virus on center stage is a coronavirus, namely, SARS-CoV-2.

As I write this, according to the Johns Hopkins Coronavirus Resource Center, the United States just became the country with greatest number of confirmed COVID-19 cases in the world. (Please insert your favorite sad-face emoji here.)

Now What?

  • Vaccines – to prevent the disease (making you immune to getting COVID-19)

Well, as SARS-CoV-2 is a “novel” human pathogenic virus, there is presently a mad scramble (e.g., see Ref. 3 below) to develop vaccines against this particular coronavirus.

Unfortunately, the vaccinologists say that it may take at least 18 months to develop and produce safe and effective vaccines. For more information regarding this, please see CIDRAP, in general, and, in particular, commentary by Dr. Michael Osterholm, currently available here (audio) and here (YouTube).

At this point, you may ask: “Is there ANY way to speed this up?

I’m glad you asked that….because it’s possible that plant-based COVID-19 vaccine technology MAY come to the rescue. (Or at least speed up vaccine production.)

Basically, how does this plant-based technology work?

Briefly, parts of the viral genome that code for its coat proteins are introduced into plants (typically, tobacco plants – Why tobacco plants?… see below) using plant genetic engineering. These viral genes are designed using recombinant DNA technology to be expressed at high levels in the genetically-modified (GM) plants, which, ultimately, are harvested and processed to extract the viral proteins. These GM-plant-produced viral proteins can then form the basis for potential vaccines.

In fact, this is already underway for SARS-CoV-2:

At the present time (03/27/2020), there are at least two biopharmaceutical companies engaged in the development of plant-based COVID-19 vaccines, namely, Medicago (in Canada) and iBio (in the USA). (Please see “Cast of Characters” below for more information about these companies.)

According to the Medicago website: “On March 12, 2020, Medicago announced the successful production of Virus-Like Particle (VLPs) of the coronavirus just 20 days after obtaining the SARS-CoV-2 (virus causing the COVID-19 disease) gene. Production of VLPs is the first step in developing a vaccine against COVID-19 before preclinical testing for safety and efficacy.
VLPs mimic the native structure of viruses, allowing them to be easily recognized by the immune system. However, they lack core genetic material which makes them non-infectious and unable to replicate.”

And, according to an iBio press release (03/26/2020): “iBio created its proprietary VLP [virus-like particle] candidates in just a few weeks using its FastPharming System™. iBio’s researchers then deployed this plant-based expression platform’s rapid production capabilities to deliver VLPs suitable for further development just weeks after the biologics were designed.”

Both companies plan to generate enough material to produce the thousands of doses needed for clinical trials, starting this summer. Best of luck to them!

Novel Coronavirus SARS-CoV-2 (CC-BY-2.0) by NIAID

  • Therapeutics – to treat the disease (if you get COVID-19)

Fortunately, unlike Ebola, most people who contract COVID-19 will not suffer life-threatening symptoms.

For those that do, however, there may be treatments available to alleviate the disease. Such treatments may also be potentially useful for providing some level of protection for highly at-risk people, including the aged, those with poor health, and frontline healthcare workers.

For example, like with Ebola, it may be possible to infuse a patient with severe COVID-19 symptoms (or high-risk people who’ve not yet contracted the disease) with antibodies to the virus (see my previous post to see how this worked for several people who were infected with Ebola).

And, yes, work is currently underway to produce such antibody-based treatments (e.g., see Refs. 4 and 5 below).

Why use plants?

Again, I’ll refer you back to my previous post re. Ebola, but briefly:

Why plants?

1. “Plant expression systems are an attractive platform for the production of antibodies, for several reasons. Predominantly due to the possibility of production scale-up at a fraction of the costs compared to conventional systems.

2. “Another advantage is that many plant species have a ‘generally regarded as safe’ status, since they do not contain mammalian viruses or pathogens, or produce endotoxins.

3. “The ease of purification and downstream processing of plant-made antibodies is often postulated to result in a low cost of the final product, which can be applied parenterally, topically or orally.

4. “Moreover, the developments in glyco-engineering of plants has made it possible to produce antibodies with desired glycoforms. Modification of glycans has also been perfected in comparative expression systems like mammalian cell cultures, but it has been seen that glyco-engineered plants have a much higher degree of glycan homogeneity.” (all of the above from Ref. 6 below)

Tobacco (CC BY-SA 2.0) by Land Between the Lakes…

Why tobacco plants?

Then there is the merit of speed: using the established state of the art tobacco leaf-based transient expression system [see Ref. 7 below, for example], bulk quantities of antibodies can be manufactured in a record time as compared to any other established expression system.” (from Ref. 6 below)

In addition to Medicago and iBio, another company – Kentucky BioProcessing – is using a tobacco-plant-based strategy to produce COVID-19 treatments (see Ref. 2 and Cast of Characters below).

In summary, the time it takes to grow and to genetically modify tobacco plants is much faster, and way less expensive, than to genetically engineer mice, for example. And plant cells also seem to produce higher quality antibodies, with less complicating factors, than animal cells.

Cast of Characters (with pertinent weblinks)

Medicago Awarded “Best New Vaccine Technology/Platform” at the World Vaccine Congress (published 04/25/2019)

Medicago Announces Production of a Viable Vaccine Candidate for COVID-19 (published online 03/12/2020)

(For the latest press releases from Medicago, click here)

iBio Announces Advancement of COVID-19 Vaccine Program (posted online 03/26/2020)

KBP in Owensboro joins fight against Coronavirus by Ngan Ho (published online 03/11/2020)

References

(1) How DARPA funded early investigations of plant-made proteins for candidate vaccine production.Fighting Pandemics With The Power Of Plants (The archived weblink thanks to the Wayback Machine) by Jessica L. Tozer (published online 08/06/2012)

(2) What’s the connection between tobacco companies and a coronavirus vaccine?Could tobacco cure coronavirus? Don’t laugh. by Sarah Owermohle (published online 02/15/2020)

(3) A list of drug developers and research institutions in North America, Europe, and China actively involved in coronavirus SARS-CoV-2 treatmentsCatching Up to Coronavirus: Top 60 Treatments in Development by Alex Philippidis (published online 03/18/2020)

(4) Current efforts to produce antibodies to the COVID-19 virus – How Monoclonal Antibodies Might Prove Useful Against The Coronavirus by Joe Palca (published online 03/26/2020)

(5) Work on developing antibodies already underway – Fast-moving Regeneron eyes summer clinical trial for COVID-19 antibody cocktail therapy by Angus Liu (published online 03/18/2020)

(6) Virdi, V. and A. Depicker (2013) “Role of plant expression systems in antibody production for passive immunization.” The International Journal of Developmental Biology, Vol. 57, pp.587-593. (Full Text PDF)

(7) Sainsbury Laboratory (2012) “High Efficiency Transient Expression System for Plants – Methods to highly express proteins in plants in days not months.” www.pbltechnology.com (Full Text PDF).

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P.S. Please remember, it’s important to engage in “social distancing” to help stop the spread of SARS-CoV-2 –> Stay safe!

“Don’t Stand So Close To Me” – The Police

One Comment

  1. Subhash Chandra Sawhney

    Perhaps Nature also has a system of developibg new plants by modifying genes by itself.

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