Nsp1 Facilitates SARS-CoV-2 Replication Through Calcineurin-NFAT Signaling

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2024 Feb 27

PMID 38411085

Authors

Wai-Yin Lui

Chon Phin Ong

Pak-Hin Hinson Cheung

Zi-Wei Ye

Chi-Ping Chan

Kelvin Kai-Wang To

Kit-San Yuen

Dong-Yan Jin

Affiliations

Soon will be listed here.

Abstract

Importance: Cyclosporine A (CsA), commonly used to inhibit immune responses, is also known to have anti-SARS-CoV-2 activity, but its mode of action remains elusive. Here, we provide a model to explain how CsA antagonizes SARS-CoV-2 through three critical proteins: DDX5, NFAT1, and Nsp1. DDX5 is a cellular facilitator of SARS-CoV-2 replication, and NFAT1 controls the production of DDX5. Nsp1 is a viral protein absent from the mature viral particle and capable of activating the function of NFAT1 and DDX5. CsA and similar agents suppress Nsp1, NFAT1, and DDX5 to exert their anti-SARS-CoV-2 activity either alone or in combination with Paxlovid.

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