Spike protein D614G and RdRp P323L: the SARS-CoV-2 mutations associated with severity of COVID-19

Abstract

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from Global Initiative on Sharing Avian Influenza Data (GISAID) database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p < 0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group (p < 0.001). The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group compared with mildly affected group, but the difference was not statistically significant (p = 0.06). We concluded that spike protein D614G and RdRp P323L mutations in SARS-CoV-2 are associated with severity of COVID-19. Further studies will be required to explore whether these mutations have any impact on the severity of disease.

Keywords: COVID-19; RNA-dependent RNA polymerase; SARS-CoV-2; genome sequence; mutation; spike protein.

Fig. 1.

Flow diagram showing sampling procedure. GISAID, Global Initiative on Sharing Avian Influenza Data; ICU, intensive care unit; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Fig. 2.

Sequence logos for spike protein (A) around amino acid position 614 and RNA-dependent RNA polymerase (RdRP) (B) around amino acid position 323. Upper panels are for mildly affected group and lower panels are for severely affected group. Selected amino acid sequence is shown on X-axis. The height of each letter on Y-axis indicates its relative frequency. RdRp, RNA-dependent RNA polymerase; N, N-terminal end; C, C-terminal end.