Molecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations

Abstract

The COVID19 pandemic, caused by SARS-CoV-2, has infected more than 100 million people worldwide. Due to the rapid spreading of SARS-CoV-2 and its impact, it is paramount to find effective treatments against it. Human neutralizing antibodies are an effective method to fight viral infection. However, the recent discovery of new strains that substantially change the S-protein sequence has raised concern about vaccines and antibodies' effectiveness. Here, we investigated the binding mechanisms between the S-protein and several antibodies. Multiple mutations were included to understand the strategies for antibody escape in new variants. We found that the combination of mutations K417N and E484K produced higher binding energy to ACE2 than the wild type, suggesting higher efficiency to enter host cells. The mutations' effect depends on the antibody class. While Class I enhances the binding avidity in the presence of N501Y mutation, class II antibodies showed a sharp decline in the binding affinity. Our simulations suggest that Class I antibodies will remain effective against the new strains. In contrast, Class II antibodies will have less affinity to the S-protein, potentially affecting these antibodies' efficiency.

The D614G Virus Mutation Enhances Anosmia in COVID-19 Patients: Evidence from a Systematic Review and Meta-analysis of Studies from South Asia

“… 146 For example, the virus with the N501Y mutation has similar binding to ACE2, while the K417N and the E484K mutants may have slightly increased binding to ACE2. 147 Multiple mutations can have interdependent and complex effects on binding and subsequent steps such as membrane fusion and host cell entry. For example, the Alpha variant that often also has N501Y, N439K, and Y453F mutations appears to require a deletion (ΔH69/V70) in the spike protein to maintain optimal cleavage and infectivity.…”

“…These variants have additional spike protein mutations, besides the G614 mutation, resulting in already proven or suspected differences in their receptor binding properties, transmissibility, viral loads, and, in some cases, increased mortality . For example, the virus with the N501Y mutation has similar binding to ACE2, while the K417N and the E484K mutants may have slightly increased binding to ACE2 . Multiple mutations can have interdependent and complex effects on binding and subsequent steps such as membrane fusion and host cell entry.…”

The D614G virus mutation enhances anosmia in COVID-19 patients: Evidence from a systematic review and meta-analysis of studies from South Asia

“…120 This may explain why SARS-CoV-2 infection leading to anosmia is associated with an overall milder COVID-19 disease, possibly because the nasal cavity-elicited immune defense leads to faster virus clearance 143 and thus reduces severe COVID-19 lung disease and death after G614 virus infection. 144,145 Such a scenario may explain the puzzling finding that the G614 virus, despite being more infectious and leading to higher nasopharyngeal viral loads than the D614 virus, does notoverallcause more severe and deadly COVID-19.…”