Prediction and mitigation of mutation threats to COVID-19 vaccines and antibody therapies.

Chemical Science
Jiahui ChenGuo-Wei Wei

Abstract

Antibody therapeutics and vaccines are among our last resort to end the raging COVID-19 pandemic. They, however, are prone to over 5000 mutations on the spike (S) protein uncovered by a Mutation Tracker based on over 200 000 genome isolates. It is imperative to understand how mutations will impact vaccines and antibodies in development. In this work, we first study the mechanism, frequency, and ratio of mutations on the S protein which is the common target of most COVID-19 vaccines and antibody therapies. Additionally, we build a library of 56 antibody structures and analyze their 2D and 3D characteristics. Moreover, we predict the mutation-induced binding free energy (BFE) changes for the complexes of S protein and antibodies or ACE2. By integrating genetics, biophysics, deep learning, and algebraic topology, we reveal that most of the 462 mutations on the receptor-binding domain (RBD) will weaken the binding of S protein and antibodies and disrupt the efficacy and reliability of antibody therapies and vaccines. A list of 31 antibody disrupting mutants is identified, while many other disruptive mutations are detailed as well. We also unveil that about 65% of the existing RBD mutations, including those variants recently found i...Continue Reading

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Jul 28, 2020·Journal of Molecular Biology·Jiahui ChenGuo-Wei Wei

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Citations

Apr 30, 2021·Scientific Reports·Mohamed Raef Smaoui, Hamdi Yahyaoui
Jul 18, 2021·Journal of Molecular Biology·Jiahui ChenGuo-Wei Wei
Jul 28, 2021·International Journal for Numerical Methods in Biomedical Engineering·Nicola ParoliniAlfio Quarteroni
Oct 15, 2021·Molecular Biology Reports·Arghavan ZebardastTayebeh Latifi
Dec 3, 2021·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Saleh S AlarfajiHamid Ullah
Nov 27, 2021·Journal of Evolutionary Biology·Jordan A Lewis, Levi T Morran
Dec 8, 2021·The Journal of Physical Chemistry Letters·Rui WangGuo-Wei Wei

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Software Mentioned

RaptorX
Mutation Tracker
TopNetTree

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