N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence

Kon Ken Wong,1,2 Shaun Wen Huey Lee,3– 6 Kok Pim Kua7 1Department of Microbiology and Immunology, Hospital Canselor Tuanku Muhriz UKM, Cheras, Kuala Lumpur, Malaysia; 2Faculty of Medicine, The National University of Malaysia, Cheras, Kuala Lumpur, Malaysia; 3School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia; 4Asian Centre for Evidence Synthesis in Population, Implementation, and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University, Bandar Sunway, Selangor, Malaysia; 5Gerontechnology Laboratory, Global Asia in the 21st Century (GA21) Platform, Monash University, Bandar Sunway, Selangor, Malaysia; 6Faculty of Health and Medical Sciences, Taylor’s University, Bandar Sunway, Selangor, Malaysia; 7Puchong Health Clinic, Petaling District Health Office, Ministry of Health Malaysia, Petaling, Selangor, MalaysiaCorrespondence: Kok Pim Kua Email kokpimkua@gmail.comAbstract: The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy.Keywords: N-acetylcysteine, SARS-CoV-2; COVID-19, coronavirus, repurposing approved drugs, engineering nanoparticles, virus infected cells, respiratory viral diseases, antioxidant, glutathione, T lymphocytes, immune modulating activity, anti-inflammatory response, antiviral effect, clinical translatio