1.
Perspectives for the Use of N-acetylcysteine as a Candidate Drug to Treat COVID-19.
Luo, P, Liu, Y, Liu, D, Li, J
Mini reviews in medicinal chemistry. 2021;(3):268-272
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromerelated coronavirus-2 (SARS-CoV-2), has become an ongoing pandemic worldwide. However, there are no vaccines or antiviral drugs with proven clinical efficacy. Therefore, a remedial measure is urgently needed to combat the devastating COVID-19. The pharmacological activities of Nacetylcysteine (NAC) and its potential functions in inhibiting the progression of COVID-19 make it a promising therapeutic agent for the infection. In this mini-review, we discussed the therapeutic potential of NAC in COVID-19 from the perspective of its multisite pharmacological actions.
2.
Therapeutic potential of N-acetyl cysteine (NAC) in preventing cytokine storm in COVID-19: review of current evidence.
Mohanty, RR, Padhy, BM, Das, S, Meher, BR
European review for medical and pharmacological sciences. 2021;(6):2802-2807
Abstract
Since November 2019, SARS Coronavirus 2 disease (COVID-19) pandemic has spread through more than 195 nations worldwide. Though the coronavirus infection affects all age and sex groups, the mortality is skewed towards the elderly population and the cause of death is mostly acute respiratory distress syndrome (ARDS). There are data suggesting the role of excessive immune activation and cytokine storm as the cause of lung injury in COVID-19. The excessive immune activation and cytokine storm usually occurs due to an imbalance in redox homeostasis of the individuals. Considering the antioxidant and free radical scavenging action of N acetyl cysteine (NAC), its use might be useful in COVID-19 patients by decreasing the cytokine storm consequently decreasing the disease severity. Therefore, we reviewed all the available resources pertaining to the role of reactive oxygen species (ROS) in cytokine storm and the mechanism of action of NAC in preventing ROS. We also reviewed the use of NAC in COVID-19.
3.
N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019.
Bourgonje, AR, Offringa, AK, van Eijk, LE, Abdulle, AE, Hillebrands, JL, van der Voort, PHJ, van Goor, H, van Hezik, EJ
Antioxidants & redox signaling. 2021;(14):1207-1225
Abstract
Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 [TLR4] pathway and NLR family pyrin domain containing 3 [NLRP3] inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.
4.
Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.
De Flora, S, Balansky, R, La Maestra, S
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020;(10):13185-13193
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Abstract
COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.