tetano
Editor, Senior Moderator
PLoS One
. 2022 Nov 17;17(11):e0277745.
doi: 10.1371/journal.pone.0277745. eCollection 2022.
Molecular dynamics study on the strengthening behavior of Delta and Omicron SARS-CoV-2 spike RBD improved receptor-binding affinity
Kanchanok Kodchakorn[SUP] 1 [/SUP], Prachya Kongtawelert[SUP] 1 [/SUP]
Affiliations
Abstract
The COVID-19 pandemic caused by a virus that can be transmitted from human to human via air droplets has changed the quality of life and economic systems all over the world. The viral DNA has mutated naturally over time leading to the diversity of coronavirus victims which has posed a serious threat to human security on a massive scale. The current variants have developed in a dominant way and are considered "Variants of Concern" by the World Health Organization (WHO). In this work, Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants were obtained to evaluate whether naturally occurring mutations have strengthened viral infectivity. We apply reliable in silico structural dynamics and energetic frameworks of the mutated S-RBD protein for ACE2-binding to analyze and compare the structural information related to the wild-type. In particular, the hotspot residues at Q493, Q498, and N501 on the S-RBD protein were determined as contributing factors to the employment stability of the relevant binding interface. The L452R mutation induces an increment of the hydrogen bonds formed by changing the Q493 environment for ACE2 binding. Moreover, the Q493K exchange in Omicron enables the formation of two additional salt bridges, leading to a strong binding affinity by increased electrostatic interaction energy. These results could be used in proposing concrete informative data for a structure-based design engaged in finding better therapeutics against novel variants.
. 2022 Nov 17;17(11):e0277745.
doi: 10.1371/journal.pone.0277745. eCollection 2022.
Molecular dynamics study on the strengthening behavior of Delta and Omicron SARS-CoV-2 spike RBD improved receptor-binding affinity
Kanchanok Kodchakorn[SUP] 1 [/SUP], Prachya Kongtawelert[SUP] 1 [/SUP]
Affiliations
- PMID: 36395151
- DOI: 10.1371/journal.pone.0277745
Abstract
The COVID-19 pandemic caused by a virus that can be transmitted from human to human via air droplets has changed the quality of life and economic systems all over the world. The viral DNA has mutated naturally over time leading to the diversity of coronavirus victims which has posed a serious threat to human security on a massive scale. The current variants have developed in a dominant way and are considered "Variants of Concern" by the World Health Organization (WHO). In this work, Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants were obtained to evaluate whether naturally occurring mutations have strengthened viral infectivity. We apply reliable in silico structural dynamics and energetic frameworks of the mutated S-RBD protein for ACE2-binding to analyze and compare the structural information related to the wild-type. In particular, the hotspot residues at Q493, Q498, and N501 on the S-RBD protein were determined as contributing factors to the employment stability of the relevant binding interface. The L452R mutation induces an increment of the hydrogen bonds formed by changing the Q493 environment for ACE2 binding. Moreover, the Q493K exchange in Omicron enables the formation of two additional salt bridges, leading to a strong binding affinity by increased electrostatic interaction energy. These results could be used in proposing concrete informative data for a structure-based design engaged in finding better therapeutics against novel variants.