Monoclonal antibody therapies hold great promise for COVID-19; however, the recent emergence and spread of escape variants threaten to limit their value. Shown here are structural and linear representations of key escape mutations in the spike protein of SARS-CoV-2 and the latest information on the impact of variants of concern. To view this SnapShot, open or download the PDF.
At least five variants of concern (VOC) have demonstrated escape from one or more mAbs of therapeutic interest: 1) B.1.1.7 (also known as 20I/501Y.V1 and Alpha), originating in the United Kingdom, contains spike mutations ΔH69-V70, ΔY144, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H; 2) B.1.351 (also known as 20H/501Y.V2 and Beta), originating in South Africa, contains spike mutations L18F, D80A, D215G, ΔL242-244, K417N, E484K, N501Y, D614G, and A701V; 3) P.1 (also known as B.1.1.248, 20J/501Y.V3 and Gamma), originating in Brazil, contains spike mutations L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, and T1027I; 4) B.1.429 (also known as CAL.20C, 452R. V1 and Epsilon), first identified in California, contains spike mutations S13I, W152C, L452R, and D614G, and 5) B.1.617, originating in India, comprises two dominant sublineages: B.1.617.1 (also known as Kappa), containing spike mutations G142D, E154K, L452R, E484Q, D614G, P681R, and Q1071H, and B.1.617.2 (also known as Delta), containing spike mutations T19R, G142D, Δ156-157, R158G, L452R, T478K, D614G, P681R, and D950N. As of this writing, B.1.617.2 appears highly contagious and possibly more pathogenic, and it is on track to become the dominant variant in many parts of the world. Notably, all VOCs contain the D614G spike mutation that alone provides a fitness advantage for transmission and that has rapidly replaced the ancestral spike to become globally dominant by mid-May 2020. Acquisition of additional mutations that impart greater transmissibility, such as occurred with B.1.1.7 (Voltz et al., 2021) and B.1.617.2, amplify the threat VOCs pose to mAb therapy.