PT  - JOURNAL ARTICLE
AU  - Erik Laurini
AU  - Domenico Marson
AU  - Suzana Aulic
AU  - Alice Fermeglia
AU  - Sabrina Pricl
TI  - <em>In Silico</em> Molecular-Based Rationale for SARS-CoV-2 Spike Circulating Mutations Able to Escape Bamlanivimab and Etesevimab Monoclonal Antibodies
AID  - 10.1101/2021.05.18.444605
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.18.444605
4099  - http://biorxiv.org/content/early/2021/05/18/2021.05.18.444605.short
4100  - http://biorxiv.org/content/early/2021/05/18/2021.05.18.444605.full
AB  - The purpose of this work was to provide an in silico molecular rationale of the role eventually played by currently circulating S-RBDCoV-2 mutations in evading the immune surveillance effects elicited by the two Eli Lilly LY-CoV555/bamlanivimab and LY-CoV016/etesevimab monoclonal antibodies. The main findings from this study and shows that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predicted to be markedly resistant to neutralization by LY-CoV555, while mutations K417E/N/T, D420A/G/N, N460I/K/S/T, T415P, and Y489C/S are predicted to confer LY-CoV016 escaping advantage to the viral protein. A challenge of our global in silico results against the relevant experimental data resulted in an overall 90% agreement. This achievement not only constitutes a further, robust validation of our computer-based approach but also yields a molecular-based rationale for all relative experimental findings, and leads us to conclude that the current circulating SARS-CoV-2 and all possible emergent variants carrying these mutations in the spike protein can present new challenges for mAb-based therapies and ultimately threaten the fully-protective efficacy of currently available vaccines.Competing Interest StatementThe authors have declared no competing interest.