COVID-19

Vaccines and Treatments through Biotechnology and Science

Amid the global pandemic, we are witnessing the effort, work, and progress of scientists who are tirelessly seeking treatments to curb the impact and spread of Covid-19. Biotechnology, synthetic biology, access to free and open digital information, and believing in science are the key to face the Covid-19.

March 25, 2020
Alejandro Hernández
Biotechnology Director for Central America and the Caribbean of CropLife Latin America

COVID-19 is a disease caused by a virus called SARS-CoV-2. It took only 42 days for science and scientists to be in the first clinical phase of a modern biotechnology-based vaccine. It is a record time considering that to reach this clinical phase using traditional technologies the research and development of a vaccine can take years.

The vaccine is called mRNA-1273 by Moderna Therapeutics Company, and it codes for a fragment of the virus coat (CoV spike), perhaps the most important fragment since it is the key to enter human cells. This in other terms is:

1. Viruses are very small; imagine a soccer ball as the human cell and a grain of sand as the virus. The cell is 100 microns and the virus that causes COVID-19 measures 100 nanometers.
2. In order for the virus to enter the cell, it uses a mechanism to trick it with its coating, which is identified by the human protein "ACE2". It's like trying to open a door with a master key (“virus coat”) that looks somewhat like the original.
3. The mRNA-1273 vaccine enters cells and causes the human cell itself to make small portions of the virus coating (CoV-spike) transitorily, causing the body to identify it as something "foreign" that triggers the immune response.

Vaccines with the same scientific logic have been developed experimentally against Zika, Ebola, rabies and influenza A, with the advantage that the stability of the mRNA increases when using lipid encapsulation as is the case with mRNA-1273.

 Coronavirus, 2020. Ilustration by David S. Goodsell, RCSB Protein Data Bank doi: 10.2210 / rcsb_pdb / goodsell-gallery-019

Other therapies against COVID-19

Thanks to Biotechnology, not only is the mRNA-1273 vaccine being developed, but other vaccines also, such as those from the companies iBio and Medicago that are both producing the vaccines in plants, DNA vaccines from the LineaRx company, or recombinant protein vaccines from Sanofi, among others.

There are other technologies such as an interference RNA that blocks the virus in the form of nebulizers¹, recombinant ACE2 proteins that trick the virus into not binding to human cells, and antibodies that attack the virus.

In short, by knowing the three-dimensional structure of the virus proteins² and of those that participate in its entry, inhibitors of these proteins are being manufactured.

And what about the complete sequencing of virus genomes and their evolution in real time available in Next Strain; an open source project to harness the scientific and public health potential of genome data from different pathogens. With more than 1000 genomes, this is an example of applied biotechnology, of the enormous advance we have had in recent years to obtain fast and cost-effective sequences, and of the collaboration of the scientific community.

CRISPR or gene editing technologies help us design much faster detection methods using Cas13 that detects RNA instead of Cas9 that detects DNA. I remind the reader that SARS-CoV-2 virus is RNA. Thus, the Broad Institute has tests that detect the S and ORF1ab genes in approximately one hour by means of complementary fragments linked to CAS13a and detection strips that change color, using some of the principles of pregnancy tests.

At the moment, the therapies that are immediately available and are being tested are based on antiviral compounds that seem to have some effect such as Remdesivir (inhibits RNA synthesis), chloroquine (blocks viral entry into the cell) and lopinavir / ritonavir (cell reproduction). These treatments are based on more conventional, but equally effective chemical technologies, which is why history reminds us that there must always be an inclusive and comprehensive approach.

The discovery of vaccination dates back to the year 1798 with the treatment of smallpox when doctor Edward Jenner noted that milk producer Benjamin Jesty and his family did not contract smallpox, since they had been exposed to a variant of smallpox present in cows; hence the name Vaccine "Variolae Vaccinae". That said, the use of genetic engineering or recombinant DNA in vaccines dates back to the early 80s, with the Hepatitis B vaccine produced in yeast (Engerix-B, GSK; Recombivax-HB, MSD) or in human cells ( GenHevac-B, Sanofi Pasteur). The first vaccine against malaria was also recombinant produced in yeasts (Mosquirix by GSK); likewise, the herpes zoster vaccine (Shingrix by GSK), the meningococcal B vaccine (Bexsero, GSK and Trumenba, Pfizer), cholera (Recombinant B Toxin), human papilloma (bivalent and quadivalent recombinant) and some vaccines for the seasonal influenza virus (Flublok Quadrivalent, Protein Sciences Corporation). Today, 40 years after the Hepatitis B vaccine we have the challenge of developing a vaccine against SARS-CoV-2, using all the scientific advances; and while science does its job, we must follow the prevention instructions such as, social distancing and constant hand washing.

We are experiencing a global pandemic and a scientific reaction like we have never seen before. It is evident that biotechnology, synthetic biology, and access to free and open digital information (digital sequence information) are essential scientific advances to confront Covid-19.

¹ Companies such as Alnylam Pharmaceuticals and Sirnaomics.

² See the 3D structures inhttps://www.rcsb.org/news?year=2020&article=5e3c4bcba5007a04a313edcc

References

• Gootenberg, J. S., Abudayyeh, O. O., Lee, J. W., Essletzbichler, P., Dy, A. J., Joung, J., ... & Myhrvold, C. (2017). Nucleic acid detection with CRISPR-Cas13a/C2c2. Science, 356(6336), 438-442.
• Guo, D. (2020). Old weapon for new enemy: drug repurposing for treatment of newly emerging viral diseases. Virologica Sinica, 1-3.
• Hodgson, J. 2020. The pandemic pipeline. Nature Biotechnology. https://www.nature.com/articles/d41587-020-00005-z
• Kellner MJ, Koob JG, Gootenberg JS, Abudayyeh OO, and Zhang F. SHERLOCK: nucleic acid detection with CRISPR nucleases. Nature Protocols. 2019 Oct;14(10):2986-3012. doi: 10.1038/s41596-019-0210-2.
• Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018). mRNA vaccines—a new era in vaccinology. Nature reviews Drug discovery, 17(4), 261. https://doi.org/10.1038/nrd.2017.243
• Petsch, B., Schnee, M., Vogel, A. B., Lange, E., Hoffmann, B., Voss, D., ... & Kramps, T. (2012). Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nature biotechnology, 30(12), 1210.
• Plotkin, S. A., & Plotkin, S. L. (2011). The development of vaccines: how the past led to the future. Nature Reviews Microbiology, 9(12), 889-893.
• Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., ... & Ciaramella, G. (2017). Modified mRNA vaccines protect against Zika virus infection. Cell, 168(6), 1114-1125.
• Rosa, S. G. V., & Santos, W. C. Clinical trials on drug repositioning for COVID-19 treatment.
• Sun, J., He, W. T., Wang, L., Lai, A., Ji, X., Zhai, X., ... & Veit, M. (2020). COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends in Molecular Medicine.
• Vetter, V., Denizer, G., Friedland, L. R., Krishnan, J., & Shapiro, M. (2018). Understanding modern-day vaccines: what you need to know. Annals of medicine, 50(2), 110-120.
• Yang, S., Fink, D., Hulse, A., & Pratt, R. D. (2017). Regulatory considerations in development of vaccines to prevent disease caused by Chikungunya virus. Vaccine, 35(37), 4851-4858.
• Zhang, F., Abudayyeh, O. O., & Jonathan, S. G. A protocol for detection of COVID-19 using CRISPR diagnostics.