SARS-CoV-2 variant B.1.617 may be more contagious and pathogenic due to spike cleavage

In the new research treatises currently available, bioRxiv* A preprint server, a research group in the United Kingdom (UK), found that the B.1.617 strain of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) (also known as a concern in India) was spiked by furin. Glycoprotein. This can increase its infectivity and pathogenicity.

The SARS-CoV-2 spike glycoprotein, the causative agent of the constant coronavirus disease 2019 (COVID-19) pandemic, initially follows the S1 / S2 junction required for efficient infection, pathogenicity, and viral replication. It contained a good cutting site.

Not surprisingly, this opened the door to the potential evolution of SARS-CoV-2 mutants with increased transmission due to more optimized cleavage sites. One of the first examples was a UK variant (B.1.1.7) containing a P681H mutation that promotes post-translational S1 / S2 cleavage during virus budding.

Recently, a variant of B.1.617 has emerged in India, causing a significant burden of disease throughout the country. Early evidence suggested that it was highly contagious in a subline containing a panorama of spiked glycoprotein mutations, including a P681R substitution that was predicted to further optimize this furin cleavage site.

This is why a British research group led by Dr. Thomas P. Peacock of the Department of Infectious Diseases at Imperial College London has decided to carefully examine the effect of the mutant P681R on cleavage sites S1 / S2.

Evaluation of cleavage characteristics

First, these researchers isolated several B.1.617 SARS-CoV-2 mutants and transferred their S1 / S2 cleavage patterns to strain B.1.238, which is known to contain only the D614G mutation. Compared with the pattern of virus strains that were circulating before belonging.

In addition, a group was generated to characterize which amino changes in the spiked glycoprotein of B.1.617 can link to its enhanced cleavage. Pseudovirus SARS-CoV-2 full B.1.617.1 Spike Glycoprotein was carried and compared to a pseudovirus with D614G spike (considered wild-type virus here).

Finally, they performed a specific assay to assess whether the optimized cleavage sites characteristic of B.1.617 spiked glycoproteins could improve direct cleavage by furin. More specifically, they measured the propensity of recombinant furin to cleave the fluorescently labeled peptide corresponding to the S1 / S2 cleavage site of SARS-CoV-2.

Variant vs. wild-type virus

Studies showed that spike Glycoprotein One of the B.1.617 variants was detected with a higher percentage of S2 cleaved, all more highly cleaved (ie, about 33% cleaved) compared to the control virus (about 33% cleaved). A low percentage of possible full-length spike glycoproteins. ..

Wild-type viral spike glycoproteins also showed both full-length and cleavage proteins, whereas B.1.617.1 was significantly enhanced, coupled with a near-total lack of full-length protein. It showed severe cuts (ie up to 95%). This means that only P681R is involved in the enhanced cleavage of spiked glycoproteins observed in the B.1.617 strain.

More specifically, P681R substantially enhances the ability of furin to cleave the peptide, and arginine substitutions are described in B.I. 1.617 Reinforces the notion that spike glycoproteins can be considered to be responsible for enhanced cleavage.

Need for close monitoring

In conclusion, this study found that enhanced S1 / S2 cleavage observed in B.1.617 and B.1.1.7 SARS-CoV-2 mutants (both containing the P681H mutation) was their transmissibility and pathogenicity. We have shown that it may contribute significantly to the increase in sex.

“In addition to B.1.1.7 and B.1.617, some other new strains contain mutations in the furin cleavage site,” the authors say. bioRxiv paper. “These strains are advised to be under close scrutiny for early evidence of a faster infection or higher pathogenesis,” they add.

In any case, further research in this area will allow us to recognize SARS-CoV-2 mutants of concern, which are more contagious and potentially fatal, fairly quickly and better mitigate. It can also help you devise a strategy.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.