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SARS-CoV-2 is Mutating

SARS-CoV-2’s genome consists of RNA, which is much more mutable than genomes made of DNA. Every time its genome is copied, an error can potentially occur. SARS-CoV-2 has accumulated an average of about two mutations per month. Today’s virus differs from the original virus isolated in Wuhan by about 15 mutations. This is a small number of mutations considering that SARS-CoV-2 genome is about 30,000 nucleotides in length. Today’s version of the virus is almost 99.5% identical to the original virus.

SARS-CoV-2 attaches to the ACE2 receptor on human cells with its spike protein. The more effective the spike protein, the more easily the virus can infect cells. A mutation affecting this protein changed amino acid 614 from “D” (aspartic acid) to “G” (glycine). The virus strain bearing this mutation is designated D614G.

The original virus was dominant before March but has eventually been replaced by the mutated variant. D614G was first detected in viruses collected in Germany and China in late January and became the dominant viral strain in Europe by April. The mutated strain has become the main variant in the United States, Canada and Australia. Ninety-six percent of early sequences belonged to the D variant, but by the end of March, almost 70 percent of sequences carried the G amino acid instead.

The mutant strain has circled back to Southeast Asia. It has spread from India to the Philippines, Malaysia and China. The D614G variant has become the most strain worldwide.

One study suggested that the D614G mutation increased the infectivity of SARS-CoV-2 in cultured cells. Since then, there has been much speculation that this mutation might make the spike protein more effective at binding to ACE2 receptors and therefore more infectious in humans. However, recently the WHO concluded there was no evidence that the mutation has made the virus more infectious or led to more severe disease. Most available evidence suggests that D614G does not prevent neutralizing antibodies from recognizing SARS-CoV-2. This might be because the mutation does not affect the spike protein’s receptor binding domain (RBD), which binds to ACE2 receptors.

At this time, SARS-CoV-2 appears to essentially be the same virus that emerged in December. It has mutated, but not in ways that have increased its infectivity or response to treatment.

References

Volz EM et al. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity, medRxiv, preprint posted September 01, 2020. https://www.medrxiv.org/content/10.1101/2020.07.31.20166082v2

Zhang L et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity, https://www.scripps.edu/news-and-events/press-room/2020/20200611-choe-farzan-sars-cov-2-spike-protein.html

Callaway Ewen, the coronavirus is mutating – does it matter? Nature, Sep 10, 2020; 585:174-177.

Sarah Kaplan and Joel Achenbach, Washington Post, June 29, 2020

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