Investigation of the D614G mutation and antibody-dependent enhancement sequences in indonesian SARS-CoV-2 isolates and comparison to southeast Asian isolates

Introduction: SARS-CoV-2 is a rapidly spreading virus that poses a major burden on global human health and the economy. Therefore, it is essential to develop COVID-19 vaccines. Vaccine construction might not be easy, as a consequence of mutations and antibody-dependent enhancement (ADE). Objective: We first reported the D614G mutation and ADE sequences in Indonesian SARS-CoV-2 isolates and compared these isolates to those from other Southeast Asian countries. Methods: In this study, we extracted the SARS-CoV-2 genome of 40 Indonesian isolates from the GISAID EpiCoV database and the Wuhan-Hu-1 isolate (reference sequence) from GenBank, NCBI. We used BioEdit v7.2.5 to identify the D614G mutation and ADE sequences in the spike protein. Then, we rendered the spike protein using the SWISS-MODEL web server and PyMOL v2.4. Results: We identified the D614G missense mutation in 23 Indonesian SARS-CoV-2 isolates and isolates from six other Southeast Asian countries. In addition, we identified the ADE sequence ⁶¹¹LYQDVNC⁶¹⁷ in the Wuhan-Hu-1 isolate, which had changed into ⁶¹¹LYQGVNC⁶¹⁷ in recent mutated isolates. Conclusion: We conclude that the D614G mutation might affect ADE activities. A rapid but cautious approach to the vaccine development and other therapies developed for COVID-19 seems needed until we have more data on the risks of the D614G mutation and ADE. However, further studies including in vitro and in vivo assessments are relevant for validation of these results.