A recent study by researchers at Andhra University has uncovered a clever way the Coronavirus might be dodging the antibodies created by COVID-19 vaccines, casting new questions on how well these vaccines protect us over time. Led by Dr. Ravikiran S Yedidi from TCABS-E Laboratories, the team examined a crucial part of the virus-the receptor binding domain (RBD) of the spike protein-which the virus uses to attach to our cells and start infection.
The Coronavirus might be slipping past the antibodies that COVID-19 vaccines create, making it harder for our immune system to recognize and stop it. Researchers discovered that a crucial part of the virus-the receptor binding domain (RBD)-can shift between solid and liquid-like states, forming clusters that hide from antibodies. This shape-shifting and flexibility help the virus avoid immune detection and infect cells more easily.
The researchers discovered that the RBD doesn’t stay in one shape. Instead, it undergoes a process called liquid-liquid phase separation (LLPS), shifting between more solid-like and liquid-like forms. This causes the RBD molecules to cluster in droplet-like groups, creating a kind of molecular crowding. This crowding effectively hides parts of the virus from the antibodies that vaccines produce, making it tougher for our immune system to spot and neutralize the virus, even in vaccinated people.
To dig deeper, the team ran detailed 500-nanosecond molecular simulations showing that the RBD behaves like an intrinsically disordered protein (IDP), meaning it is flexible and constantly moving. These flexible parts overlap with the spots where antibodies and the ACE2 receptor (the cell’s doorway for the virus) bind. This means the virus can hide these regions by changing shape, helping it sneak past immune defenses and infect cells more easily.
Current vaccines target the stable form of the spike protein, but if the immune system isn’t trained to recognize this flexible, clustered form, it may not produce effective antibodies against it. Dr. Yedidi suggests that next-generation vaccines might need to harness advanced technologies like AI and quantum computing to design protections that can outsmart the virus’s shape-shifting tricks.
This discovery highlights why new COVID variants continue to spread despite vaccination and paves the way for smarter vaccines that keep up with savvy viral strategies.
REFERENCE: Manikanta Sodasani, Abhinav V.K.S. Grandhi, Niharikha Mukala, Jahnavi Chintalapati, Madhuri Vissapragada, Madhumita Aggunna, Ravikiran S. Yedidi; Receptor binding domain of SARS CoV2 spike protein exhibits in vitro liquid-liquid phase separation due to structural disorderedness that may challenge the vaccine-generated antibody binding; Biochimica et Biophysica Acta (BBA) - General Subjects; Volume 1870, Issue 1,2026,; https://doi.org/10.1016/j.bbagen.2025.130889.
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