Minor Changes with Large Implications: Modeling Amino Acid Mutations in SARS-CoV Monoclonal Antibodies (80R and 362) Towards the Design of More Universal Antibodies
Abstract
SARS-CoV-2, the causative agent of COVID-19, has led to over 100 million cases and over 2 million deaths worldwide. Two anti-SARS-CoV monoclonal antibodies (MAbs) 80R and 362 are known to bind to epitopes on the spike protein receptor-binding domain (RBD), with 80R binding to SARS-CoV-1 and 362 binding to both SARS-CoV-1 and SARS-CoV-2. To investigate this further and hypothesize structures for a potentially more effective antibody, undergraduate students participated in the CREST (Connecting Researchers, Educators, and STudents) Program and studied the binding interactions between the antibodies and their respective spike proteins. At the binding interface between these antibodies and the SARS spike protein, MAb362 mutations trend smaller and less polar than those in 80R: Arg149Ser, Asn151Ser, Asp170Gly, and Trp213Ser. Due to the trend of smaller amino acids appearing in the MAb362 binding interface, it was hypothesized that more space in this area could allow antibodies to be more resistant to future SARS-CoV spike protein variants. A hypothetical antibody (NSU1) was modeled using MAb362 with four additional mutations: Asp103Gly, Trp104Leu, Gly170Ser, and Arg211Val. Except for Gly170, these mutations within the binding interface exhibit decreased size and polarity. Position 170 is Asp on the 80R structure, so a mutation to Ser was still expected to maintain the trend of smaller residues. These models allowed for deeper understanding of the impact of mutations on binding interactions between antibodies and viral proteins. The modeling process also provided insight into the molecular structure of a potentially more universal antibody against variations in SARS-CoV.
Faculty Sponsors
Dr. Emily Schmitt Lavin, Dr. Arthur Sikora
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-6-2021 12:00 PM
End Date
4-9-2021 12:00 PM
Minor Changes with Large Implications: Modeling Amino Acid Mutations in SARS-CoV Monoclonal Antibodies (80R and 362) Towards the Design of More Universal Antibodies
Alvin Sherman Library
SARS-CoV-2, the causative agent of COVID-19, has led to over 100 million cases and over 2 million deaths worldwide. Two anti-SARS-CoV monoclonal antibodies (MAbs) 80R and 362 are known to bind to epitopes on the spike protein receptor-binding domain (RBD), with 80R binding to SARS-CoV-1 and 362 binding to both SARS-CoV-1 and SARS-CoV-2. To investigate this further and hypothesize structures for a potentially more effective antibody, undergraduate students participated in the CREST (Connecting Researchers, Educators, and STudents) Program and studied the binding interactions between the antibodies and their respective spike proteins. At the binding interface between these antibodies and the SARS spike protein, MAb362 mutations trend smaller and less polar than those in 80R: Arg149Ser, Asn151Ser, Asp170Gly, and Trp213Ser. Due to the trend of smaller amino acids appearing in the MAb362 binding interface, it was hypothesized that more space in this area could allow antibodies to be more resistant to future SARS-CoV spike protein variants. A hypothetical antibody (NSU1) was modeled using MAb362 with four additional mutations: Asp103Gly, Trp104Leu, Gly170Ser, and Arg211Val. Except for Gly170, these mutations within the binding interface exhibit decreased size and polarity. Position 170 is Asp on the 80R structure, so a mutation to Ser was still expected to maintain the trend of smaller residues. These models allowed for deeper understanding of the impact of mutations on binding interactions between antibodies and viral proteins. The modeling process also provided insight into the molecular structure of a potentially more universal antibody against variations in SARS-CoV.
