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Would Omicron transmission be slowed by endosomal pathway inhibitors?

Daniel R. Lucey, MD, MPH, FIDSA
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At least three research groups have reported that Omicron is the first SARS-CoV-2 variant that can use the endosomal pathway to infect cells, especially in the upper respiratory tract, thereby potentially contributing to Omicron’s unprecedented high transmission rate. Thus, it may be warranted to conduct clinical trials to determine if endosomal pathway inhibitors, given as prophylaxis before infection or as treatment after infection, would slow transmission. In the same studies, any differences in clinical outcome should be assessed. 

Use of oral endosomal entry inhibitors in this context may be controversial, given the experience in 2020 when SARS-CoV-2 did not use the endosomal entry mechanism as does Omicron today. Thus, if such studies are deemed to be worthwhile, then well-designed, well-controlled and well-monitored studies are essential.

Laboratory studies that found Omicron, unlike Delta, can use an endosomal entry pathway include:

Peacock T. et al. “The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry.”

Willett B. et al. “The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism.”

Zhao H. et al. “SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with delta variant in TMPRSS2-expressed cells.”


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