Molecular dynamics to explore the neutralizing efficacy and mechanisms of SARS-CoV-2 antibodies against single-point...

Coronavirus Disease-2019 (COVID-19) is a respiratory disease caused by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a high infectious rate. Due to the easy mutation of SARS-CoV-2, the continuous emergence of SARS-CoV-2 variants not only makes the new coronavirus more contagious but also poses a considerable obstacle to the treatment of COVID-19. In this study, the computer-aided drug design method was used to explore the effects of mutations on the neutralizing efficacy and mechanism of Amubarvimab and Romlusevimab. Our experimental data show that Amubarvimab and Romlusevimab can effectively neutralize wild-type SARS-CoV-2, and the latter has a more substantial neutralizing effect. The binding effect depends on rich hydrogen bonds, electrostatic interactions, and the van der Waals interaction network, and Romlusevimab also depends on a strong salt bridge. In the face of six single point mutations K417N, L452R, E484K, F486L, Q498Y, and N501Y, Amubarvimab can show a stable and excellent neutralizing effect. In contrast, the Q498Y and N501Y mutations reduced Romlusevimab binding more significantly than the other four mutations studied. The cause of this phenomenon is the deformation of RBD and the reduction in the number of non-covalent bonds. This study evaluated the efficacy of Amubarvimab and Romlusevimab in neutralizing SARS-CoV-2 and its variants, elucidated the molecular mechanisms, and provided theoretical guidance for developing and modifying antibodies.