The spike protein can adopt different conformations: a closed state that hides the receptor-binding domain (RBD) and an open state that exposes the RBD for binding.
The transition between these states is regulated by the presence of disulfide bonds, which are covalent links between two cysteine residues.
A recent study by Debnath et al. [1] explored the possibility of using N-acetyl cysteine (NAC), a widely available dietary supplement and mucolytic agent, to disrupt the disulfide bonds of the spike protein and prevent its binding to ACE2. NAC is known to have antioxidant and anti-inflammatory properties, and has been used as an adjunct therapy for various respiratory diseases.
By binding to these residues, NAC could reduce the stability of the disulfide bonds and induce conformational changes in the spike protein. The authors also performed in vitro experiments using pseudovirus particles and human lung epithelial cells.
They showed that NAC could inhibit the infection of pseudovirus particles carrying the spike protein by reducing their binding affinity to ACE2.
The study suggests that NAC could be a potential therapeutic agent for COVID-19 by targeting the spike protein and blocking its interaction with ACE2. The authors propose that NAC could be administered orally or by inhalation to reach high concentrations in the respiratory tract. They also suggest that NAC could have synergistic effects with other antiviral drugs or vaccines by enhancing their efficacy.
The study is one of the first to explore the molecular mechanism of action of NAC against SARS-CoV-2, and provides a novel insight into the structure and dynamics of the spike protein. However, more experimental and clinical studies are needed to confirm the safety and efficacy of NAC for COVID-19 treatment and prevention.
Mechanism of Action
The mechanism by which NAC inhibits SARS-CoV-2 replication is not fully understood. However, it is thought to work by disrupting the conformational changes of the spike protein. NAC can do this by binding to the spike protein and preventing it from binding to ACE2. This can prevent the virus from entering the cell and replicating.
In vitro Studies
A number of in vitro studies have shown that NAC can inhibit the replication of SARS-CoV-2. In one study, NAC was found to inhibit the replication of SARS-CoV-2 in Vero cells by up to 90%. In another study, NAC was found to be more effective than the antiviral drug remdesivir at inhibiting the replication of SARS-CoV-2 in human lung cells.
In vivo Studies
A number of in vivo studies have also shown that NAC has potential anti-COVID-19 activity. In one study, NAC was found to reduce the severity of COVID-19 in mice. In another study, NAC was found to reduce the viral load in the lungs of COVID-19 patients.
Safety and Tolerability
NAC is a safe and well-tolerated compound. It has been used for many years in the treatment of a variety of conditions, including acetaminophen poisoning and chronic obstructive pulmonary disease.
reference link : https://doi.org/10.1080/07391102.2023.2234031
