Sunday Article 01: the SArs-cov-2 variants

What is D614G?

D614G is the first mutated SARS-CoV-2 variant found in Malaysia. D614G mutation is caused by the replacement of amino acid aspartate (D) by glycine (G) at the 614th amino-acid position of the spike protein. It is caused by a copying fault that altered a single nucleotide in the virus’s 29,903-letter RNA code.

SARS-CoV-2 spike protein binds to angiotensin-converting enzyme 2 (ACE2) to gain cell entry, D614G alters the receptor binding conformation, such that ACE2 binding and fusion is more likely.

Epidemiology of D614G Mutation

D614G mutation is prevalent not only in Malaysia but in other countries as well. In July, variants carrying the D614G mutation became the globally dominant form of SARS-CoV-2. It was first present in Guangzhou, Sichuan and Shanghai Provinces, China in late January. Then on January 28, the D614G variant was also detected in a small outbreak in Bavaria, Germany, which was initiated by a visitor from Shanghai. Meanwhile, in the United Kingdom, the first observation of a genome carrying the D614G mutation was in a sample collected on February 28 from a patient in Scotland who had recently travelled through Italy. It is also dominant in the United States, Canada and Australia.

Infectivity of D614G Mutation

According to Health director-general Tan Sri Dr Noor Hisham Abdullah, the D614G mutant is almost 10 times more infectious than the usual coronavirus. This is explained by a lower cycle threshold (CT) value, aka a higher viral load within the person’s body, which translates to a greater chance of them infecting others with the virus. This is because the D614G virus outcompetes other stains by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission.

However, this strain was already circulating in Singapore six months ago in February, hence there is not enough scientific evidence to prove the purportedly faster transmission rate of the virus.

Cause of Virus Mutation

There are various reasons for virus mutation, for example, random genetic drift, and the mutations are mostly neutral. These random genetic changes that do not help or hurt the virus. However, there are currently two hypotheses for the occurrence of this D614G mutation, which are the positive selection and the founder’s effect respectively.

Volz’s team used a large dataset to investigate the hypothesis for positive selection of spike D614G in the United Kingdom but not all approaches showed a conclusive signal of positive selection.

On the other hand, the founder’s effect is suggested as the D614G mutation might have been more common in the first viruses to arrive in Europe and North America.

Risk? Chance?

The D614G mutation causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus’ vulnerable core. With one flap open, it’s easier for antibodies to infiltrate and disable the virus.

What do scientists know about B117 now?

The recent discovery of the new strain of SARS-CoV-2 is named B117 or VUI202012/01, means it is the first “variant under investigation” in December 2020.

B117 is 70% more transmissible than other strains. It has a higher reproduction rate so one infected person can infect a greater number of people.

According to WHO, more than 50% of new cases diagnosed in England consist of this B117 mutant. It contains 23 mutations, including 17 key "non-synonymous" mutations that change the protein sequences.

At least three of the spike mutations, N501Y, N439K and Y453F, help the virus to bind more tightly to the ACE2 receptor for cell entry.

A two amino-acid deletion, 69/70Delta, help the virus evade antibodies from people. It also decreases the accuracy of COVID-19 test by bringing in false-negative result to one of the targets of SARS-CoV-2 PCR test, the S gene.

It is believed to come from an immunocompromised COVID-19 patient as their weakened immune systems provide chances for the virus to acquire many mutations for months.

More Countries Detected B117 Variant

Despite many countries ban UK arrivals to stop the spread of new variant of virus, there are more and more countries reported to detect the UK-based coronavirus variant. It has already spread to Denmark, Australia, Singapore, France and Japan.

Good News

Experts found that B117 does not cause a more severe infection than the other strains. What we can do now are to keep following all the protocols of washing hands, practising social distancing and wearing masks when in public to protect ourselves from the SARS-CoV-2. Hope everyone stays safe and heathy.

References:

Kupferschmidt K. U.K. variant puts spotlight on immunocompromised patients’ role in the COVID-19 pandemic. Science Magazine. 23 Dec 2020.

Tyler N. Starr, et al. Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell. Volume 182, Issue 5. 2020. Pages 1295-1310.e20.

Volz E, et al. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell. 2020.

Ketchell M. What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The experts explain. The Conversation. 14 May 2020.

This article is prepared by Seow Qi Ng.