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

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.

Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged first around December 2019 in the city of Wuhan, China. Since then, several variants of the virus have emerged with different biological properties. This pandemic has so far led to widespread infection cycles with millions of fatalities and infections globally. In the recent cycle, a new variant omicron and its three sub-variants BA.1, BA.2 and BA.3 have emerged which seems to evade host immune defences and have brisk infection rate. Particularly, BA.2 variant has shown high transmission rate over BA.1 strain in different countries including India. In the present study, we have evaluated a set of eighty drugs/compounds using in silico docking calculations in omicron and its variants. These molecules were reported previously against SARS-CoV-2. Our docking and simulation analyses suggest differences in affinity of these compounds in omicron and BA.2 compared to SARS-CoV-2. These studies show that neohesperidin, a natural flavonoid found in Citrus aurantium makes a stable interaction with spike receptor domain of omicron and BA.2 compared to other variants. Free energy binding analyses further validates that neohesperidin forms a stable complex with spike RBD in omicron and BA.2 with a binding energy of -237.9 ± 18.7 kJ/mol and -164.1 ± 17.5 kJ/mol respectively. Key residual differences in the RBD interface of these variants form the basis for differential interaction affinities with neohesperidin as drug binding site overlaps with RBD-human ACE2 interface. These data might be useful for the design and development of novel scaffolds and pharmacophores to develop specific therapeutic strategies against these novel variants.

Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged first around December 2019 in the city of Wuhan, China. Since then, several variants of the virus have emerged with different biological properties. This pandemic has so far led to widespread infection cycles with millions of fatalities and infections globally. In the recent cycle, a new variant omicron and its three sub-variants BA.1, BA.2 and BA.3 have emerged which seems to evade host immune defences and have brisk infection rate. Particularly, BA.2 variant has shown high transmission rate over BA.1 strain in different countries including India. In the present study, we have evaluated a set of eighty drugs/compounds using in silico docking calculations in omicron and its variants. These molecules were reported previously against SARS-CoV-2. Our docking and simulation analyses suggest differences in affinity of these compounds in omicron and BA.2 compared to SARS-CoV-2. These studies show that neohesperidin, a natural flavonoid found in Citrus aurantium makes a stable interaction with spike receptor domain of omicron and BA.2 compared to other variants. Free energy binding analyses further validates that neohesperidin forms a stable complex with spike RBD in omicron and BA.2 with a binding energy of −237.9 ± 18.7 kJ/mol and −164.1 ± 17.5 kJ/mol respectively. Key residual differences in the RBD interface of these variants form the basis for differential interaction affinities with neohesperidin as drug binding site overlaps with RBD-human ACE2 interface. These data might be useful for the design and development of novel scaffolds and pharmacophores to develop specific therapeutic strategies against these novel variants. Graphical Image 1