TY - JOUR
T1 - Structural evolution of Delta lineage of SARS-CoV-2
AU - Gomari, Mohammad Mahmoudi
AU - Tarighi, Parastoo
AU - Choupani, Edris
AU - Abkhiz, Shadi
AU - Mohamadzadeh, Masoud
AU - Rostami, Neda
AU - Sadroddiny, Esmaeil
AU - Baammi, Soukayna
AU - Uversky, Vladimir N.
AU - Dokholyan, Nikolay V.
N1 - Funding Information:
This research was supported by grant No 22588 from Iran University of Medical Sciences .
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/1/31
Y1 - 2023/1/31
N2 - One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.
AB - One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.
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U2 - 10.1016/j.ijbiomac.2022.11.227
DO - 10.1016/j.ijbiomac.2022.11.227
M3 - Article
C2 - 36435470
AN - SCOPUS:85143542417
SN - 0141-8130
VL - 226
SP - 1116
EP - 1140
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -