Inhibition of Protein N-Glycosylation Blocks SARS-CoV-2 Infection

Inhibition of Protein N-Glycosylation Blocks SARS-CoV-2 Infection

Blog Article

ABSTRACT Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) extensively N-glycosylates its spike proteins, which are necessary for host cell invasion and the target of both vaccines and immunotherapies.These N-glycans are predicted to modulate spike binding to the host receptor by stabilizing its open conformation and host immunity evasion.Here, we investigated the essentiality of both the host N-glycosylation pathway and SARS-CoV-2 N-glycans for infection.

Ablation of host N-glycosylation using RNA interference or inhibitors, including FDA-approved drugs, reduced the spread of the infection, including that of variants B.1.1.

7 (Alpha), B.1.351 (Beta), P.

1 (Gamma) and B.1.617.

2 (Delta).Under these conditions, cells produced fewer virions and some completely lost their infectivity.Furthermore, sequal eclipse 5 battery partial enzymatic deglycosylation of intact virions showed that surface-exposed N-glycans are critical for cell invasion.

Altogether, we propose protein N-glycosylation as a targetable pathway with clinical potential for treatment of COVID-19.IMPORTANCE The coronavirus SARS-CoV-2 uses its spike surface proteins to infect human cells.Spike proteins are heavily modified with several N-glycans, which are predicted to modulate their function.

In this work, we show that interfering with either the synthesis or attachment of spike N-glycans significantly reduces the 15-eg2373cl spread of SARS-CoV-2 infection in vitro, including that of several variants.As new SARS-CoV-2 variants, with various degrees of resistance against current vaccines, are likely to continue appearing, halting virus glycosylation using repurposed human drugs could result in a complementary strategy to reducing the spread of COVID-19 worldwide.