Significant role of host sialylated glycans in the infection and spread of severe acute respiratory syndrome coronavirus 2
Wakana Saso, Masako Yamasaki, Shin‐ichi Nakakita, Shuetsu Fukushi, Kana Tsuchimoto, Noriyuki Watanabe, Nongluk Sriwilaijaroen, Osamu Kanie, Masamichi Muramatsu, Yoshimasa Takahashi, Tetsuro Matano, Makoto Takeda, Yasuo Suzuki, Koichi Watashi
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been transmitted across all over the world, in contrast to the limited epidemic of genetically- and virologically-related SARS-CoV. However, the molecular basis explaining the difference in the virological characteristics among SARS-CoV-2 and SARS-CoV has been poorly defined. Here we identified that host sialoglycans play a significant role in the efficient spread of SARS-CoV-2 infection, while this was not the case with SARS-CoV. SARS-CoV-2 infection was significantly inhibited by α2-6-linked sialic acid-containing compounds, but not by α2-3 analog, in VeroE6/TMPRSS2 cells. The α2-6-linked compound bound to SARS-CoV-2 spike S1 subunit to competitively inhibit SARS-CoV-2 attachment to cells. Enzymatic removal of cell surface sialic acids impaired the interaction between SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2), and suppressed the efficient spread of SARS-CoV-2 infection over time, in contrast to its least effect on SARS-CoV spread. Our study provides a novel molecular basis of SARS-CoV-2 infection which illustrates the distinctive characteristics from SARS-CoV.