We have faced the new poison king of Omicron, so how strong it really is, here Professor Ah Yuan shares a study from Michigan State University, which is currently published on the pre-print website ArXiv.
1. Contagious
Omicron has 3 mutations at the Flynnase cleavage site and 15 mutations in RBD, with the exception of G339D, S371L, S373P, and S375F mutations, most of which are located near the ACE2 and RBD binding interfaces.
The study [1] found that these mutations caused a 13-fold increase in omicron infectivity, which is 2.8 times more contagious than Delta.
From reference [1]: 3D structure of the ACE2 and RBD complexes, marked in red as the mutation site of Omicron.
Second, the impact on vaccines
The researchers assessed the changes in binding free energy caused by 15 RBD mutations on these complexes through a library of 132 known antibody and S protein complexes to understand the effects of omicron on the vaccine, as shown in the figure. The study found that there are three mutations that have a great impact:
K417N, also seen in beta strains, causes the most significant disruption of known antibodies. E484A has an overwhelmingly damaging effect on many known antibodies and is complementary to K417N. Y505H weakens many known antibodies and RBD complexes.
Heat map from reference [1]: b1-b2 124 antibody and RBD complexes, positive BFE number (blue) indicates that the antibody and virus are more easily bound to function, and negative BFE number (red) indicates that the antibody is more difficult to bind to the virus, and immune escape occurs.
The omicron strain is more damaging to the vaccine than the delta strain:
Figures c and d are the distribution of mutations in the omicron strain and delta strains inducing cumulative BFE changes in 132 antibody and RBD complexes, respectively. It can be seen that the RBD mutation of the Omicron strain weakens more complexes than the enhanced complexes, which favors the escape of the current vaccine, while the BFE distribution of the delta strain is concentrated in a smaller range. Figures e and f are the number of antibodies and RBD complexes disrupted by Omicron and delta at different BEF values, respectively.
From references[1]
Third, the impact on antibody drugs
(1) Eli Lilly monoclonal antibody therapy
Eli Lilly monoclonal antibody therapies include LY-CoV555 (aka Bamlanivimab) and LY-CoV016 (aka Etesevimab), see figure. Several mutations affect the efficacy of LY-CoV555, such as Q493R may reduce efficacy by about 5 times, G496S can increase the binding of complexes by 2.6 times, and K417N and N501Y can also weaken its efficacy. [1] The new mutation Y505H may reduce the efficacy of LY-CoV016.
The authors predict that if Omicron becomes a popular variant in the world, Eli Lilly monoclonal antibody cocktail therapy will likely withdraw from the market.
From Reference [1]: a is a 3D plot of two monoclonal antibodies binding to ACE2, b is the BFE changes of different mutations to the RBD and LY-CoV016 complex, and c is the BFE changes of different mutations to the RBD and LY-CoV555 complexes.
(2) Regenerative element monoclonal antibody therapy
Regenerative element monoclonal antibody therapy contains REGN10933 and REGN10987 (also known as Casirivimab and Imdevimab, respectively), see figure. G446K and K417N impair the binding capacity of REGN10987 to RBD (BFE is negative), but many other mutations enhance its binding capacity (BFE is positive); similar phenomena are also seen in REGN10933, K417N and E484A weakening, and other mutations are enhanced. When the two are combined (see Figure d), the mutation has less effect on it.
Therefore, if the authors cannot enhance the efficacy of regenerative element monoclonal antibody therapy, it will also have a very slight negative impact.
From Reference [1]: a is a 3D plot of two monoclonal antibodies binding to ACE2, b is the BFE change of different mutations on the RBD and REGN10933 complex, c is the BFE change of different mutations on the RBD and REGN10987 complex, and d is the BFE change of different mutations on the RBD, REGN10933 and REGN10987 complexes.