Is BF.7 more infectious than other Omicron subtypes: Insights from structural and simulation studies of BF.7 spike RBD variant

Jaikee Kumar Singh; Shashi Anand; Sandeep Kumar Srivastava

doi:10.1016/j.ijbiomac.2023.124154

Is BF.7 more infectious than other Omicron subtypes: Insights from structural and simulation studies of BF.7 spike RBD variant

Int J Biol Macromol. 2023 May 31:238:124154. doi: 10.1016/j.ijbiomac.2023.124154. Epub 2023 Mar 24.

Authors

Jaikee Kumar Singh¹, Shashi Anand¹, Sandeep Kumar Srivastava²

Affiliations

¹ Structural Biology & Bioinformatics Laboratory, Department of Biosciences, Manipal University Jaipur, Dehmi Kalan, Off Jaipur-Ajmer Expressway, Jaipur, Rajasthan 303007, India.
² Structural Biology & Bioinformatics Laboratory, Department of Biosciences, Manipal University Jaipur, Dehmi Kalan, Off Jaipur-Ajmer Expressway, Jaipur, Rajasthan 303007, India. Electronic address: sandeepkumar.srivastava@jaipur.manipal.edu.

Abstract

Fear of a fresh infection wave and a global health issue in the ongoing COVID-19 pandemic have been rekindled by the appearance of two new novel variants BF.7 and BA.4/5 of Omicron lineages. Predictions of increased antibody evasion capabilities and transmissibility have been recognised in addition to the existing lineages (BA.1.1, BA.2, BA.2.12.1 and BA.3) as cause for worry. In comparison to Omicron, BA.4 and BF.7 share nine mutations in the spike protein, Leu371Phe, Thr376Ala, Asp405Asn, Arg408Ser, Ser446Gly, Leu452Arg, Phe486Val, Arg493Gln, Ser496Gly, whereas BF.7 contains an additional mutation, Arg346Thr, in the receptor binding domain (RBD) region. Due to the critical need for analysis and data on the BA.4 and BF.7 variants, we have computationally analyzed the interaction pattern between the Omicron, BA.4 and BF.7 RBD and angiotensin-converting enzyme 2 (ACE2) to determine the influence of these unique mutations on the structures, functions, and binding affinity of RBD towards ACE2. These analyses also allow to compare molecular models to previously reported data to evaluate the robustness of our methods for quick prediction of emerging future variants. The docking results reveal that BA.4 and BF.7 have particularly strong interactions with ACE2 when compared to Omicron, as shown by several parameters such as salt bridge, hydrogen bond, and non-bonded interactions. In addition, the estimations of binding free energy corroborated the findings further. BA.4 and BF.7 were found to bind to ACE2 with similar affinities (-72.14 and - 71.54 kcal/mol, respectively) and slightly stronger than Omicron (-70.04 kcal/mol). The differences in the binding pattern between the Omicron, BA.4 and BF.7 variant complexes indicated that the BA.4 and BF.7 RBD substitutions Asp405Asn, Ser446Gly, Leu452Arg, Phe486Val and Arg493Gln caused additional interactions with ACE2. In addition, normal mode analyses also indicate more stable conformations of BA.4 and BF.7 RBDs against human ACE2. Based on these structural and simulation analyses, we hypothesized that these changes may affect the binding affinity of BA.4 and BF.7 with ACE2.

Keywords: BA.4; BF.7; Binding affinity; Docking; MD simulation.

MeSH terms

Angiotensin-Converting Enzyme 2* / genetics
COVID-19*
Computer Simulation
Humans
Mutation
Pandemics
Protein Binding
Research Design

Substances

Angiotensin-Converting Enzyme 2