Bimodular effects of D614G mutation on the spike glycoprotein of SARS-CoV-2 enhance protein processing, membrane fusion, and viral infectivity

By the end of June 2020, the pandemic of coronavirus diseases 2019 (COVID-19) had resulted in more than 10 million individuals, all over the world, being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 1 The high contagiousness of SARS-CoV-2 virus was largely attributed to the relatively unique sequence composition in its spike (S) glycoprotein, which is in charge of the host entry by interacting with its cellular receptor angiotensin-converting enzyme 2 (ACE2). 2 , 3 The S glycoprotein can be processed into an N terminal S1 fragment that is responsible for receptor binding, and a C terminal S2 fragment that functions to promote membrane fusion. 4 SARS-CoV-2 is a type of single-stranded positive-sense ribonucleic acid (RNA) virus, and an increasing number of mutations were identified across the SARS-CoV-2 genome, including the region encoding S glycoprotein. Nevertheless, the functional implications of these mutations remain largely unknown, we here reported the mutation analysis of S gene and a functional exploration of the dominant D614G mutation.