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Copyright (c) 2025 Seshadri Reddy Varikasuvu, Munikumar Manne, Subodh Kumar, Shiv Kumar Mudgal, Vikash Raj, Saurabh Varshney, Pratima Gupta, Ashoo Grover, Chanchal Goyal, Vanita Lal, Harminder Singh, SARANSH Workshop Members

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The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.COVID-19 clinical outcomes and N-acetylcysteine (CoViNAC study): a GRADE compliant meta-analysis of randomized controlled trials with molecular docking and dynamics simulation studies with Mpro of SARS-CoV-2
Corresponding Author(s) : Seshadri Reddy Varikasuvu
Cellular and Molecular Biology,
Vol. 71 No. 5: Issue 5
Abstract
N-acetylcysteine (NAC) has been proposed as an adjuvant therapy for COVID-19, but evidence from randomized controlled trials (RCTs) remains inconclusive. This systematic review and meta-analysis evaluated NAC’s efficacy in improving mortality and recovery/discharge rates. Additionally, molecular docking and molecular dynamics simulation (MDMS) studies were conducted to assess NAC’s interaction with the SARS-CoV-2 main protease (Mpro), a key enzyme for viral replication. A systematic search identified 12 RCTs, with 11 trials (1125 patients) included in the mortality analysis. NAC significantly reduced mortality (RR=0.59, 95% CI 0.39–0.88, p=0.01; I²=62%), indicating a 41% decreased risk of death. Six RCTs (656 patients) showed improved recovery/discharge rates (RR=1.09, 95% CI 1.03–1.14, p=0.003; I²=0%). MDMS studies demonstrated stable NAC binding at the Mpro catalytic site, interacting with His41 and Cys145, crucial for enzymatic activity. These findings suggest NAC significantly improves clinical outcomes in COVID-19 and may inhibit viral replication by targeting Mpro. This integrated evidence substantiates NAC’s potential as a critical adjuvant therapy.
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