ASK-related neutralizing antibody cocktail blocks SARS-CoV-2 infection in human lung organoids

Cell surface receptors play a key role in determining viral pathogenic mechanisms

SARS-CoV-2 utilizes different angiotensin-converting enzyme 2/asialoglycoprotein receptor 1/loop-containing transmembrane protein 1 (ACE2/ASGR1/KREMEN1, ASK) receptor combinations to enter different cell types, At the cellular and tissue levels, co-expression of ASK was significantly more strongly associated with virus susceptibility than any single receptor

Organoids refer to organs that resemble tissues

Recently, researchers from Fudan University in Shanghai published an article entitled "Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2" in the journal Cell Research

Image credit: https://doi.

This study revealed an interacting host receptor for SARS-CoV-2 and identified asialoglycoprotein receptor 1 (ASGR1) and ring structure-containing transmembrane protein 1 (KREMEN1) as alternative functional receptors, Plays an important role in ace2-independent viral entry, providing clues to gain insights into the tropism and pathogenesis of SARS-CoV-2, as well as community resources and potential therapeutic strategies for further investigation of COVID-19

To test the antibodies under more physiological conditions, the authors performed experiments with human lung organoids to detect the expression of ASK receptors in human lung tissue.

To visualize viral infection more clearly, the authors infected human lung organoids with a GFP reporter-containing SARS-CoV-2S-pseudotyped virus

Schematic diagram of ASK receptor-mediated entry of SARS-CoV-2

Image credit: https://doi.

This study points to the possibility that alternative virus-binding receptors may exert context-dependent regulatory roles that lead to distinct signaling outcomes that ultimately affect infection patterns, immune responses, and clinical progression

references

Yunqing Gu et al.