# NSP6 of SARS-CoV-2 Dually Regulates Autophagic–Lysosomal Degradation

## TL;DR

This paper shows how a SARS-CoV-2 protein, NSP6, both starts and blocks a cell cleanup process called autophagy, which could help explain how the virus causes disease.

## Contribution

The study identifies NSP6's dual role in regulating autophagy initiation and degradation, with implications for viral pathogenesis.

## Key findings

- NSP6 activates autophagy initiation by promoting Beclin1 activity.
- NSP6 blocks autophagy-lysosome degradation by inhibiting Mucolipin 1 (MLN1).
- The L37F SNP in NSP6 reduces its ability to block lysosome-dependent degradation.

## Abstract

The pandemic of coronavirus disease 2019 (COVID-19), brought about by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted public health and the economy. A fundamental aspect of addressing this virus lies in elucidating the mechanisms through which it induces disease. Our study reveals that Non-structural protein 6 (NSP6) of SARS-CoV-2 promotes the initiation of autophagy by activating Beclin1. In the later stage of autophagy, however, NSP6 causes a blockage in the autophagy–lysosome degradation via the inhibition of Mucolipin 1 (MLN1). The single nucleotide polymorphism (SNP) L37F in NSP6, which is associated with asymptomatic infection, similarly enhances the initiation of autophagy but displays a reduced ability to impede lysosome-dependent degradation. In summary, we demonstrated the dual-regulation mechanism of NSP6 in autophagy, which may be one of the reasons for targeting cellular autophagy to induce viral pathogenesis. This finding may provide promising new directions for future research and clinical interventions.