Evolutionary dynamics of SARS-CoV-2 circulating in Yogyakarta and Central Java, Indonesia: sequence analysis covering furin cleavage site (FCS) region of the spike protein

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the COVID-19 pandemic. The emergence of the new SARS-CoV-2 has been attributed to the possibility of evolutionary dynamics in the furin cleavage site (FCS) region. This study aimed to analyze the sequence of the FCS region in the spike protein of SARS-CoV-2 isolates that circulated in the Special Region of Yogyakarta and Central Java provinces in Indonesia. The RNA solution extracted from nasopharyngeal swab samples of confirmed COVID-19 patients were used and subjected to cDNA synthesis, PCR amplification, sequencing, and analysis of the FCS region. The sequence data from GISAID were also retrieved for further genome analysis. This study included 52 FCS region sequences. Several mutations were identified in the FCS region, i.e., D614G, Q675H, Q677H, S680P, and silent mutation in 235.57 C > T. The most important mutation in the FCS region is D614G. This finding indicated the G614 variant was circulating from May 2020 in those two provinces. Eventually, the G614 variant totally replaced the D614 variant from September 2020. All Indonesian SARS-CoV-2 isolates during this study and those deposited in GISAID showed the formation of five clade clusters from the FCS region, in which the D614 variant is in one specific cluster, and the G614 variant is dispersed into four clusters. The data indicated there is evolutionary advantage of the D614G mutation in the FCS region of the spike protein of SARS-CoV-2 circulating in the Special Region of Yogyakarta and Central Java provinces in Indonesia.

Full-genome sequencing and mutation analysis of SARS-CoV-2 isolated from Makassar, South Sulawesi, Indonesia

“…In Indonesia, D614G was reported to be dominant (94.2%) until June 2021 ( Cahyani et al, 2021 ), and this is consistent with our findings in Makassar city during our study period of January–April 2021. In other Indonesian provinces (namely Yogyakarta and Central Java) the D614G variant circulating since May 2020 finally replaced the D614 variant completely as of September 2020 ( Wijayanti et al, 2022 ). Several studies have attempted to examine the effects of this mutation, and results suggest that it is a crucial to the FCS region.…”

Genetic Variation of Structural and Functional Genes of SARS-CoV-2 Isolates Circulating in Banyumas (Indonesia)

“…In Indonesia, the massive spread of COVID-19 cases might be aided further by human travel patterns all over the world. For example, since September 2020, the G614 variant has completely replaced the D614 variant in all Indonesian regions (Wijayanti et al, 2022). Additionally, the emergence of new variants is not necessarily a cause for alarm, as not all variants will have significant impacts on the virus's behaviour or the effectiveness of vaccines and treatments.…”

The high mutation rate at the D614G hotspot-furin cleavage site region increases the priming efficiency of the Spike protein by furin protease: analysis of Indonesian SARS-CoV-2 G614 variants obtained during the early COVID-19 pandemic

“…This mutation has been reported to increase the infectivity of SARS-CoV-2, but it does not seem to affect severity [ 26 ]. Various geographical locations previously dominated by the D614 variant had quickly shifted into the G614 variant [ 29 ]. Despite the increasing infectivity that has been reported in both in vitro and in vivo studies, the exact mechanisms related to it remain unclear [ 19 , 13 ].…”