Generalized Methodology for the Quick Prediction of Variant SARS-CoV-2 Spike Protein Binding Affinities with Human Angiotensin-Converting Enzyme II.
J Phys Chem B
; 126(12): 2353-2360, 2022 03 31.
Article
in English
| MEDLINE | ID: covidwho-1751666
ABSTRACT
Variants of the SARS-CoV-2 virus continue to remain a threat 2 years from the beginning of the pandemic. As more variants arise, and the B.1.1.529 (Omicron) variant threatens to create another wave of infections, a method is needed to predict the binding affinity of the spike protein quickly and accurately with human angiotensin-converting enzyme II (ACE2). We present an accurate and convenient energy minimization/molecular mechanics Poisson-Boltzmann surface area methodology previously used with engineered ACE2 therapeutics to predict the binding affinity of the Omicron variant. Without any additional data from the variants discovered after the publication of our first model, the methodology can accurately predict the binding of the spike/ACE2 variant complexes. From this methodology, we predicted that the Omicron variant spike has a Kd of â¼22.69 nM (which is very close to the experimental Kd of 20.63 nM published during the review process of the current report) and that spike protein of the new "Stealth" Omicron variant (BA.2) will display a Kd of â¼12.9 nM with the wild-type ACE2 protein. This methodology can be used with as-yet discovered variants, allowing for quick determinations regarding the variant's infectivity versus either the wild-type virus or its variants.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
COVID-19
Type of study:
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
J Phys Chem B
Journal subject:
Chemistry
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS