Dominari A, Hathaway III D, Kapasi A, Paul T, Makkar SS, Castaneda V, Gara S, Singh BM, Agadi K, Butt M, Retnakumar V, Chittajallu S, Taugir R, Sana MK, KC M, Razzack S, Moallem N, Alvarez A, Talalaev M. Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19. World J Virol 2021; 10(2): 34-52 [PMID: 33816149 DOI: 10.5501/wjv.v10.i2.34]
Corresponding Author of This Article
Donald Hathaway III, MD, Division of Research and Academic Affairs, Larkin Health System, 7031 SW 62nd Avenue, South Miami, FL 33143, United States. donald.hathaway@larkinhospital.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Virol. Mar 25, 2021; 10(2): 34-52 Published online Mar 25, 2021. doi: 10.5501/wjv.v10.i2.34
Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19
Asimina Dominari, Donald Hathaway III, Abdulhusein Kapasi, Trissa Paul, Sarabjot Singh Makkar, Valeria Castaneda, Sirisha Gara, Bishnu Mohan Singh, Kuchalambal Agadi, Maliha Butt, Varadha Retnakumar, Spandana Chittajallu, Rahima Taugir, Muhammad Khawar Sana, Manish KC, Sarah Razzack, Niala Moallem, Alina Alvarez, Michael Talalaev
Asimina Dominari, Donald Hathaway III, Abdulhusein Kapasi, Trissa Paul, Sarabjot Singh Makkar, Valeria Castaneda, Sirisha Gara, Bishnu Mohan Singh, Kuchalambal Agadi, Maliha Butt, Varadha Retnakumar, Spandana Chittajallu, Rahima Taugir, Muhammad Khawar Sana, Manish KC, Sarah Razzack, Niala Moallem, Alina Alvarez, Michael Talalaev, Division of Research and Academic Affairs, Larkin Health System, South Miami, FL 33143, United States
Author contributions: Dominari A and Hathaway III D defined the topic and designed the study, Dominari A coordinated the writing of the manuscript, Alvarez A and Talalaev M provided critical reviews, all authors contributed to the literature search, all authors wrote the original manuscript, all authors assisted in reviewing and editing the manuscript, all authors consented for publication of the finalized manuscript.
Conflict-of-interest statement: No funding or sponsorship was received by any author for any part of this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Donald Hathaway III, MD, Division of Research and Academic Affairs, Larkin Health System, 7031 SW 62nd Avenue, South Miami, FL 33143, United States. donald.hathaway@larkinhospital.com
Received: December 29, 2020 Peer-review started: December 29, 2020 First decision: January 18, 2021 Revised: January 23, 2021 Accepted: March 12, 2021 Article in press: March 12, 2021 Published online: March 25, 2021
Abstract
N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.
Core Tip: N-acetylcysteine is a long known antioxidant that is currently best studied for its use as an antidote for acetaminophen overdose. Its off-label use in various diseases, such as chronic respiratory disease, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza, has shown promising results, as have recent clinical trials investigating the potential benefits of N-acetylcysteine in patients with coronavirus disease 2019.
