The Omicron coronavirus strain appeared in early November 2021 in South Africa. Omicron has more than 30 mutations. Among them, 15 mutations are located in the spike protein’s receptor-binding domain (RBD). Spike protein mutations increase contagion and the ability to evade the immune response, therefore increasing the risk of re-infection with coronavirus. In addition, modifications in RBD impair neutralization by monoclonal antibodies administered to patients with COVID-19.
ACE2 Decoy
The coronavirus uses the ACE2 receptor on the cell surface to enter the body. Japanese scientists have constructed ACE2, which binds most effectively to the thorn-shaped protein of the coronavirus, and proposed using the developed ACE2 as a decoy. Instead of binding to the cellular ACE2 receptor, the coronavirus will bind to the constructed, more effective ACE2, which will lead to the suppression of viral infection.
The constructed ACE2 showed the ability to neutralize the virus, comparable to therapeutic monoclonal antibodies. The advantage of the ACE2–based decoy is its resistance to mutations that allow the virus to elude the immune system. If the coronavirus develops mutant spikes that can evade the decoy of ACE2, they will bind less effectively to cellular ACE2. A virus with such mutations will be much less contagious.
Antibodies After Vaccination and Natural COVID-19 are Less Effective in Neutralizing Omicron
Omicron avoids neutralization by serums of vaccinated and recovering patients. First of all, this ability is associated with RBD mutations.
To assess how effectively antibodies from sera vaccinated and recovering from COVID-19 neutralize Omicron, scientists have created a pseudovirus with an Omicron spike. The study involved 12 people vaccinated by Pfizer-BioNTech, 11 patients who had been ill with coronavirus before the appearance of the Delta strain, and 18 during/after Delta.
Study Results:
- Three months after introducing the second dose of the Pfizer-BioNTech vaccine, serums neutralized the Omicron strain 17.7 times worse than the original strain of the D614G coronavirus.
- Sera recovered before the Delta pandemic neutralized Omicron 19.3 and 17.8 times worse than the original or Alpha strain, respectively. Serums recovered during/after the Delta pandemic neutralized Omicron 9.5 and 15.4 times worse than the original or Delta strain.
Engineered ACE2 Neutralizes A Wide Range of Coronavirus Strains, Including Omicron
Monoclonal antibodies are more than 1000 times worse at neutralizing Omicron than the Wuhan strain. The engineered ACE2 can neutralize many coronavirus strains, including Alpha, Beta, Gamma, and Omicron. In addition, the constructed ACE2 balances the Omicron better than the wild-type ACE2.
To test the therapeutic effectiveness of the constructed ACE2, scientists conducted a study on hamsters. 2 hours after infection with Omicron, hamsters were treated with ACE2. ACE2 significantly suppressed viral RNA in the lungs after 5 days. The expression of inflammatory cytokine and chemokine genes decreased during treatment with engineered ACE2.
ACE2 improves the survival rate of Omicron infection. Scientists have confirmed this in an experiment on mice. Three of the four mice died within 8 days of the disease. On the contrary, treatment with engineered ACE2 significantly reduced mortality.
Outcome
In addition to improving the effectiveness of vaccines and developing monoclonal antibodies, it is crucial to identify strategies that can help prevent and treat infections with all current and possible future strains of coronavirus, especially Omicron.
The thorn-shaped protein of the coronavirus binds to cellular ACE2, but the engineered ACE2 interacts with the thorn-shaped protein more effectively, preventing the virus from entering the cell and preventing infection. ACE2 decoy can help treat and prevent Omicron and future strains of coronavirus.
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Reference
Engineered ACE2 counteracts vaccine-evading SARS-CoV-2 Omicron variant
