Anand Vaidya, TIFR Hyderabad
We keep hearing that a new mutation of Coronavirus has rapidly spread in the world and that this mutant could worsen the pandemic. What is this mutant and how did it arise? Does this mutant worsen the pandemic? And how does it affect vaccine development? It is important to note that the disease severity of Covid-19 is similar in patients infected with either the original virus or the mutant one. Then what is causing this spread of the mutant virus? These three papers and several others address these questions.
Viruses multiply by infecting a suitable host organism, which makes several copies of the viral genetic material (DNA or RNA). This process of copying genetic material sometimes results in mistakes called mutations. Many of these mutations are inconsequential, while some have a negative effect on the viral multiplication and hence can't spread. Sometimes, these mutations spread rapidly in the population and in some cases the mutations reduce the effectiveness of a vaccine against the virus. During a pandemic, scientists keep collecting viral samples from infected patients and sequence their genetic material to follow the mutations. This helps in understanding the evolution of the virus and its movement between different countries. In the current Covid-19 pandemic, the original virus has the amino acid aspartic acid (D) at position 614. But in mid-February, a mutant virus with amino acid glycine (G) at position 614 was identified in Europe and within a month it was more widely observed in patients all over the world than the original D614. But the severity of Covid-19 was found to be similar in patients with the D614 or the G614 version of the virus.
There are two possible reasons for this rapid spread of the G614 virus - (i) the mutation is altering the biology of the virus and it can now spread faster or (ii) it is just chance and the G614 virus was at the 'right place at the right time'. Some epidemiologists suggest that chance could have played a major role, such as multiple patients simultaneously carrying the G614 virus into a city or the lack of awareness, testing and segregating patients in the initial phase of the viral spread, etc. But the following papers suggest that the biology has probably changed and more experiments are needed to confirm this. They argue that the G614 virus out-competed the D614 within local regions and all the way up to the country-level, indicating an inherent increase in the ability to spread. They also provide experimental evidence such as increased viral RNA from patients with the G614 virus, higher viral entry into cells and higher viral production of the G614 containing test viruses (in laboratory settings).
Since the G614 mutation is in the viral Spike protein, which is critical for the virus to enter the human cells, scientists studied how this might affect the viral recognition of human cells and vaccine development. Using test viruses, they show that the both the D614 and G614 versions of the virus interact similarly to the ACE2 receptor on the human cells. They also show that the G614 mutation increases the stability of the spike protein on the virus, which could possibly explain the spread. On the contrary, convalescent serum from recovered patients, which contain antibodies against the virus, neutralizes both the D614 and G614 versions of the virus. This suggests that the current vaccines developed against the D614 version, many of which are already in the pipeline, can possibly be used against the G614 version as well. Most of these studies are performed using test-viruses in standard laboratory settings. Though these studies provide crucial insights into this new mutant, further studies using the SARS-CoV-2 virus and human lung cells or animals is necessary to corroborate the findings.
- Korber et al, Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus(link is external), Cell (2020)
- Zhang et al, The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity,(link is external) bioRxiv (2020)
- Hu et al, The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera(link is external), bioRxiv (2020)
[Last updated 09 July 2020 ]