- Seven different coronaviruses have been shown to cause disease in human beings, including common ones that tend to cause transient respiratory infections often referred to as the “common cold,” and others that cause more serious illnesses such as SERS, MERS and the current COVID-19.
- The virus that causes COVID-19 has been believed to be relatively stable with a low mutation rate, leading vaccine manufacturers to believe a long-lasting vaccine could be created quickly.
- New research has shown a significant mutation with different immune characteristics has already occurred on a genome sequence sample from January 27th, suggesting that if mutations can occur at any time, creating a vaccine may not be simple or even feasible.
One of the issues vaccine manufacturers have with creating a vaccine against coronaviruses is that, like influenza viruses, they contain single strands of RNA. This viral type has a tendency to mutate, making it a challenge to create a vaccine that might remain relevant on an ongoing basis.1
According to the U.S. Centers for Disease Control and Prevention (CDC), seven coronaviruses have been identified as capable of causing human disease. The four most common are 229E, NL63, OC43 or HKU1, which generally cause mild and passing respiratory symptoms often referred to as the “common cold.”2 Others are MERS-CoV, the coronavirus responsible for Middle East Respiratory Syndrome (MERS), SARS-CoV, which causes severe acute respiratory syndrome (SARS) and, now, SARS-CoV-2, the virus that has caused the current pandemic, coronavirus disease 2019 (COVID-19).3
Genomic Stability Informs Vaccine Development
SARS-CoV-2 had been considered to be a relatively stable coronavirus with a low rate of mutation, persuading some scientists that an effective vaccine could be found quickly. Professor Stefano Menzo, a virologist at Ancona University Hospital observed in March 2020 that, “Our initial data show that this is a very stable RNA virus, with only five novel variants,” adding that, ”A virus with a stable genome is good news for vaccine development because it indicates that the effectiveness of vaccines could be more consistent, possibly over many years.”4
A ‘Significant’ COVID-19 Mutation Identified
Nevertheless, several mutations have already been reported. By mid-April, researchers from the University of Cambridge mapping how the virus has spread from the epicenter in Wuhan, China, stated the virus has mutated into three distinct strains. The first is “Strain A,” thought to be the original strain found in Wuhan; the second is “Strain B,” two mutations from A and responsible for most of the cases in Wuhan and East Asia; and the third is “Strain C,” offshoot of B and the strain responsible for most of the infections in Europe.5
In April, researchers in Australia and Taiwan also published an article analyzing the mutation dynamics of SARS CoV-2 and found a mutant, stating, “This represents the first report of a significant SARS-CoV-2 mutant and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified.”6 7
For this study, which has not yet been peer reviewed, 106 complete or nearly complete genome sequences were obtained from NCBI databanks. The study material included 54 nucleotide sequences from the U.S., 35 from China, 3 from Spain, 1 from Australia, 2 each from Brazil and India, and 1 each from Finland, Italy, Nepal, South Korea and Sweden. In almost all cases, the samples were highly homogeneous, sharing over 99 percent of their identity. But on one of the samples from India, collected on January 27, the researchers identified a mutation that they believe would result in a weaker “receptor binding affinity” for human Angiotensin-Converting Enzyme 2 (ACE2).
ACE2 Provides the Gateway to COVID-19
A protein receptor primarily found on the surface of cells in the veins, kidneys and testes, but also—importantly for COVID-19—found in the lungs, kidneys and intestines,8 ACE2 is believed to provide the entryway that allows the spiky proteins on the SARS-CoV-2 virus to connect to, enter, and infect the cells of the body.9 Those spiky proteins on the SARS-CoV-2 virus, specifically an area on the spikes known as the receptor-binding domain, or RBD, where the mutation was found, attach to protein receptors on the ACE2. These spikes represent a primary research targets for developing vaccines, therapies and diagnostics for COVID-19,10 11 so mutations that affect their ability to infect the cell may have important repercussions for investigations into COVID-19.
Mutation Dynamics of COVID-19 Need Monitoring
Agreeing that SARS-CoV-2 has a much lower mutation rate than SARS, for example, the researchers warned:
Whilst it is generally safe to say that SARS-CoV-2 tends to mutate at a low rate, all current analyses are merely based on data collected at the early stage of this pandemic. As the virus continues to spread rapidly around the world, and more genomic data is accumulated, the evolution and mutation dynamics of SARS-CoV-2 still need to be monitored closely… the observation in this study raised the alarm that SARS- CoV-2 mutation with varied epitope profile could arise at any time, which means current vaccine development against SARS-CoV-2 is at great risk of becoming futile.12
1 Hamblin J. You’re Likely to Get the Coronavirus. The Atlantic Feb. 24, 2020.
2 Centers for Disease Control and Prevention. Common Human Coronaviruses. Feb. 13, 2020.
3 CDC. Human Coronavirus Types. Feb. 15, 2020.
4 Pallister K. Stability Of Coronavirus Genome Is Good News For Vaccine Development, Scientists Say. IFL Science Mar. 26, 2020.
5 Kaur K. 3 Major Covid-19 Coronavirus Mutations Exist In Malaysia & It Just Might Save Us. MSN Apr. 21, 2020.
6 Yong Jia, Gangxu Shen, et al. Analysis Of The Mutation Dynamics Of SARS-Cov-2 Reveals The Spread History And Emergence Of RBD Mutant With Lower ACE2 Binding Affinity. Biorxiv.org Apr. 9, 2020.
7 Ciaccia C. ‘Significant’ Coronavirus Mutation Discovered, Could Make Vaccine Search ‘Futile,’ Study Says. Fox News Apr. 16, 2020.
8 ACE-2: The Receptor for SARS-CoV-2. RND Systems.
9 Bamforth E. ACE2: How Researchers Think Coronavirus Attacks Cells, And How It Could Be Stopped. Cleveland.com. Mar. 24, 2020.
10 Balfour H. Scientists Demonstrate How COVID-19 Infects Human Cells. Drug Target Review Mar. 5, 2020.
11 Trafton A. An Experimental Peptide Could Block Covid-19. MIT News Mar. 27, 2020.
12 See Footnote 6.