ACADEMIC RESEARCH • 學術研究 2022 UMAGAZINE 25 • 澳大新語 52 RBD mutation and have caused multiple outbreaks worldwide that have been more severe than those caused by the strains with a single mutation, putting unvaccinated populations in particular at high risk. Take the example of the Delta strain, which was first identified in India in October 2020. The strain contains a double RBD mutation L452R/ T478K and is much more contagious than previous mutant strains in terms of severity of infections and hospitalisation rates. The Delta strain spread rapidly throughout the world and became the predominant strain of SARS-CoV-2. To control the SARS-CoV-2 pandemic and develop better treatments, there is an urgent need to uncover the mechanism of increased transmissibility due to RBD mutations. It is suspected that the increased transmissibility of SARS-CoV-2 caused by RBD mutations may be related to the mutations causing stronger binding of the viral RBD to the human ACE2 receptor. However, clear evidence for this assumption is lacking. In our study, we investigated whether an increased RBD mutation could cause a structural change leading to a tighter binding between RBD and the human ACE2 receptor. We compared the effects of single mutations in RBD, including L452R, T478K, E484K, E484Q, and N501Y, with double mutations, including L452R/ T478K (Delta), L452R/E484Q (Kappa), and E484K/ N501Y (Beta, Gamma) on the relationship between RBD and ACE2 receptors, using the wild type as a control. Using the supercomputing cluster in UM’s Information and Communication Technology Office, we analysed single and double RBD mutations by using molecular dynamics simulations to measure the thermodynamic changes in the structure of the RBD mutants. We also visualised the mutation-induced changes in the RBD structure with superimposed structural comparisons, investigated the changes in free binding energy to determine the effect of mutations on the protein affinity between RBD and the ACE2 receptor, and tested the mutation-induced changes in the RBD surface structure and the neutralizing antibody binding sites. Research Results Included in WHO COVID-19 Guidelines The results of our research show that double mutations have altered the structure of RBD in ways very different from those by single mutations: Double mutations have increased the binding 王山鳴教授（右）致力研究癌症遺傳和預防 Prof San Ming Wang (right) specialises in cancer genetics and prevention
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