SARS-CoV-2 spike D614G variant exhibits improved replication and transmissibility

Approximately 11 months after the coronavirus disease (COVID-19) epidemic, scientists published a lot of information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus, which has infected more than 46 million people, has evolved and the D614G substitution of the spike (S) protein has emerged. This mutation is currently the major circulating variant of the pandemic (S-614G).

A team of scientists from Switzerland, Germany and the United States have demonstrated that the S-614G mutant has enhanced binding of SARS-CoV-2 to human angiotensin converting enzyme 2 (ACE2), the cellular gateway. The mutants also showed enhanced replication and transmissibility in animal models. p

COVID-19 Pandemic

Almost a year has passed since the SARS-CoV-2 infection occurred in Wuhan, China, in late December 2019. The viral infection rapidly evolved into a coronavirus pandemic, affecting 190 countries and territories worldwide.

The total number of cases worldwide currently exceeds 46.83 million, and the virus kills more than 1.2 million people. Most cases had mild to moderate symptoms, but only a few had severe illness. Infections can cause serious symptoms in people at high risk, such as the elderly, those with underlying illness, and those with weakened immunity.

Invasion of SARS-CoV-2 into cells depends on spike interactions Glycoprotein (S) and host cell surface receptor angiotensin converting enzyme 2 (ACE2). During the virus’s invasion of the cell, the receptor binding domain (RBD) within the S1 subunit connects to ACE2 and forms changes in the S2 subunit.

S-D614G is a protein variant that contains a substitution in the S protein outside the RBD. It is thought to weaken the interprotomer latch of the S protein trimer between the S1 and S2 domains. Therefore, this improves ACE2 binding and increases the likelihood of infection.

As the pandemic progressed, the SARS-CoV-2S-614G variant rapidly outperformed its parent S-614D variant. Today, the S-614G variant is predominant.

the study

To determine the role of S-D614 substitution in the prevalence and predominance of this mutant in the COVID-19 pandemic, the team described the binding of the S protein to human ACE2 and its replication in vitro. In addition, the team used animal models (mice, Syrian hamsters, ferrets) to evaluate infection and transmission dynamics in vivo.

The team uses Biolayer Interferometry (BLI) technology to replace the S-G614G. Spike protein And ACE2. This method aims to quantify the binding affinity of the two.

In the study, it is published as a preprint bioRxiv*server, Researchers have discovered a functional change in the S protein due to D614G substitution, indicating an increase in infection. The team also revealed that the variant shows increased replication and transmission.

However, the team pointed out that there is no evidence of phenotypic changes in the pathogenicity of animal models. This means that infection with the SARS-CoV-2S-614G mutant is not associated with the development of severe human COVID-19. ..

In addition, the researchers said the pandemic still caused additional mutations in the virus, which could indicate phenotypic changes and adaptation to humans. To implement a rapid response to mitigate the spread of the virus, whole-genome sequences are used to immediately track the genetic variation of new mutants, evaluate the phenotype of the virus, and evaluate the new virus. It is important to reconstruct the mutant.

“In summary, our data provide a true competitive advantage in vivo, especially during transmission bottlenecks, while S-614G substitution results in a subtle increase in binding and replication in vitro. , Shows that it provides an explanation for the global superiority of S-614G, a variant of the SARS-CoV-2 virus that is currently prevalent, “the researchers concluded in the study.

With new data on COVID-19, scientists are approaching the discovery of treatments, treatments, and potential vaccines for coronavirus. There are no cures available yet, but health organizations have urged the genitals to implement mitigation strategies to prevent infection, such as washing hands regularly, wearing face masks, and observing social distance. ..

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical / health-related behaviors, and should not be treated as established information.