the molecular analysis of Pr. Jacques Fantini

the molecular analysis of Pr Jacques Fantini

The new variant named Omicron is causing panic in all countries, impacting the financial markets and calling into question the vaccine strategy. But what do we really know about this variant? Is it more contagious, more dangerous? The molecular analysis of Jacques Fantini, professor of Biochemistry and Molecular Biology at the University of Aix-Marseille, honorary member of the Institut Universitaire de France (IUF).

Jacques Fantini

By Jacques Fantini

This new variant appeared in Southern Africa and is in the news because of the very large number of mutations in its Spike protein: 30 mutations, 3 deletions and 1 insertion (in red in the complete model structure visible here).
In order to know more about its contagiousness, I applied to this variant the T-index analysis (transmissibility index) which had allowed me, since the appearance of the Delta variant last April, to anticipate its expansion at the world level (see here: https://lnkd.in/dnSDgQv).
This index takes into account the interaction of the NTD domain with the rafts of the host cell, the interaction of the RBD domain with the ACE-2 receptor, and the electrostatic surface potential which reveals the attraction speed of the virus to the target cell.

No selection logic

The predominance of the Delta variant is explained, at the level of the virus, by its very high T-index value: 10.67. By comparison, the T-index of the initial strain (Wuhan) has a T-index of 2.16. We can therefore extrapolate that the Delta variant is about 5 times more transmissible than the initial strain.
The calculation made for the Omicron variant gives a T-index = 3.90. It is therefore a priori less transmissible than Delta, which remains to this day the variant with the highest T-index.
A detailed analysis of the Spike protein of the Omicron variant suggests that this avalanche of mutations does not follow any selection logic, but rather a lack of immunological control (immunocompromised patient?) And / or antiviral treatments that may favor the appearance of mutations.

Accumulation of mutations

The affinity of the Omicron RBD for ACE-2 is decreased compared to all other variants analyzed so far, probably as a consequence of this accumulation of mutations in the RBD (> 10!)
The success of Delta is due to the concomitant evolution of NTD and RBD with only 2 mutations in each domain. For Omicron, the mutations go in all directions, without any particular logic, some annihilating each other.
The mutational profiles of NTD and RBD suggest that neutralizing antibodies will have very low activity on this variant.
In contrast, the facilitating epitope of NTD (ADE epitope) is also destroyed by the Omicron Spike rearrangements, further emphasizing the lack of logic in this exaggerated mutational profile.

Conclusion

This analysis of the Omicron variant suggests that this variant will not supplant Delta.
Let us not forget the importance of virus-host interactions. The ACE-2 receptor polymorphism could, for example, allow regional breakthroughs of the Omicron variant (this was the case with the B.1.351 variant, which spread in southern Africa, but not in Europe).
In any case, barrier measures remain essential for all.

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