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N-acetyl cysteine (NAC)
- Thread starter Invisible Woman
- Start date
Dolphin
Senior Member (Voting Rights)
https://cellmolbiol.org/index.php/CMB/article/view/5831/3616
Abstract
Article history:
Received: February 12, 2025
Accepted: April 27, 2025
Published: May 31, 2025
N-acetylcysteine (NAC) has been proposed as an adjuvant therapy for COVID-19, but evidence from ran-domized 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.
Keywords: COVID-19, N-acetylcysteine, Mortality, Meta-analysis, SARS-CoV-2.
Abstract
Article history:
Received: February 12, 2025
Accepted: April 27, 2025
Published: May 31, 2025
N-acetylcysteine (NAC) has been proposed as an adjuvant therapy for COVID-19, but evidence from ran-domized 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.
Keywords: COVID-19, N-acetylcysteine, Mortality, Meta-analysis, SARS-CoV-2.