N501Y mutation in SARS-CoV-2 responsible for increased viral transmission

Researchers at the University of Texas, USA, have confirmed that the specific mutation in the B.1.1.7 variant of coronavirus respiratory syndrome 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID- 19), allowed to be more mobile than the snoring of their ancestors. Substitution of N501Y is one of 8 spike protein by-products present in the UK variant and has also appeared consistently in Brazil (P.1) and South African (B.1.351) variants. ).

The Menachery Lab, in collaboration with Shi Laboratory, used a combination of backbone genetics, and testing in hamsters and human airway epithelial cells to study the effect of the spike mutations present in B.1.1. 7. They were able to dismiss seven of the surrogate mutants as having poor viral fitness strengths, highlighting the N501Y mutation as the only “mutation of major disturbance.”

This research confirms what other studies have found, that it is the N501Y mutation that allows the variant to be more mobile, by allowing the virus to more easily interact with angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 is an enzyme present in human heart organs, kidney cells and lungs, and if compromised, can increase the host, spread, and pathogenesis of the virus.

A pre-printed version of the full research paper can be found on the bioRxiv* server.

The research

Scott Weaver and his colleagues captured Syrian hamsters with SARS-CoV-2 engineered mutants. The mutant modifications consisted of several sequences, each with only one of the individual spike centers present in version B.1.1.7, as well as a variation in the eight mutations .

Hamsters were sampled after 4 days after infection, nasal wash and necropsied. The animals were coexisted with unprotected hamsters one day after the first infection for 8 h.

Over the course of the analysis, the researchers were able to bleach and dissect N501Y as the only large, consistent and important substitute to influence viral fitness, reproducing itself more rapidly in nasal airways and lung cavities. hamsters. They found that this mutation did not affect violence, only the transmission rate.

Finally, the researchers performed binding assays using recombinant spike receptor (RBD) receptor binding and human ACE2 proteins, suspecting that the conversion of asparagine to tyrosine in N501Y conversion allowed increased ACE2 receptor binding affinity. Their findings suggest that the N501Y mutation allows the development of viral fitness for viral replication on the upper airway.

Ongoing

At present, the UK ‘s variable sex continues to be neutralized by conventional vaccines. However, it may be easier to transition over resistant mutants rising faster. The authors note that only two of the eight spike mutations provided fitness benefits to the virus in infection and transmission – replacement N501Y, and elimination of the ons69-70 codons ( also homosexual in the variables of Brazil and South Africa, although it was effective). They warn, therefore, that the remaining six should be examined to understand their roles in the B.1.1.7 variant. They also acknowledge that primary or human models would generate more relevant results than the hamsters used in the study, however, these were the best rodent models available.

The total global number of recurrent cases of SARS-CoV-2 infections is currently over 118.4 million. The B.1.1.7 variance has been reported so far in at least 25 countries, and case numbers are increasing.

By increasing our understanding of the virus and its various variants, and the roles of their mutations, researchers can better combat transmission and violence.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.