In Vitro Antiviral and Anti-Inflammatory Activities of N-Acetylglucosamine: Development of an Alternative and Safe Approach to Fight Viral Respiratory Infections

Abstract

Viral respiratory tract infections (RTIs) are responsible for significant morbidity and mortality worldwide. A prominent feature of severe respiratory infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is the cytokine release syndrome. Therefore, there is an urgent need to develop different approaches both against viral replication and against the consequent inflammation. N-acetylglucosamine (GlcNAc), a glucosamine (GlcN) derivative, has been developed as an immunomodulatory and anti-inflammatory inexpensive and non-toxic drug for non-communicable disease treatment and/or prevention. Recent studies have suggested that GlcN, due to its anti-inflammatory activity, could be potentially useful for the control of respiratory virus infections. Our present study aimed to evaluate in two different immortalized cell lines whether GlcNAc could inhibit or reduce both viral infectivity and the inflammatory response to viral infection. Two different viruses, frequent cause of upper and lower respiratory tract infections, were used: the H1N1 Influenza A virus (IAV) (as model of enveloped RNA virus) and the Human adenovirus type 2 (Adv) (as model of naked DNA virus). Two forms of GlcNAc have been considered, bulk GlcNAc and GlcNAc in nanoform to overcome the possible pharmacokinetic limitations of GlcNAc. Our study suggests that GlcNAc restricts IAV replication but not Adv infection, whereas nano-GlcNAc inhibits both viruses. Moreover, GlcNAc and mainly its nanoformulation were able to reduce the pro-inflammatory cytokine secretion stimulated by viral infection. The correlation between inflammatory and infection inhibition is discussed.

Synthesis and anti-inflammatory activities of two new N-acetyl glucosamine derivatives

“…In addition to the mechanistic issue, further studies are mandatory to provide the necessary information on whether BNAG1 and BNAG2 are potential candidates of a viable therapeutic strategy to target inflammation in a variety of pathologies, including but not restricted to joint damages 6 , 7 , inflammatory bowel disease 8 , autoimmune diseases 9 , and viral respiratory infections 10 , 11 . While our experimental data indicated that BNAG1 was more effective than NAG or BNAG2, it would be interesting to investigate if it is also more powerful than glucosamine or other NAG derivatives mentioned above.…”

“…N-acetyl glucosamine (NAG), an acetylated derivative of glucosamine, is an essential component of bacterial and fungal cell walls as well as various human tissues 5 . Due to its low cost, ready availability and less side effects as a natural product and significant anti-inflammatory activity, NAG has attracted much attention as an ideal candidate for the treatment of inflammation-related diseases such as joint damage 6 , 7 , inflammatory bowel disease 8 , autoimmune diseases 9 , and viral respiratory infections 10 , 11 . In particular, many clinical trials on NAG have been performed to treat patients with joint disorders, including arthritic diseases, osteoarthritis, rheumatoid arthritis, cartilage damage, joint injury and degenerative joint disease 5 .…”

Rational Design of Novel Peptidomimetics against Influenza A Virus: Biological and Computational Studies

“…MDCK cells were grown as reported elsewhere [ 50 ]. The Brisbane-like influenza A/H1N1 oseltamivir-resistant virus strain A/Parma/24/09 H1N1 was propagated in 80% confluent MDCK cells as previously described, and viral stocks were stored at −80 °C [ 51 ].…”

“…The viral cytopathic effect (c.p.e.) was measured by MTT assay as reported elsewhere by our laboratory [ 51 ]. Results were expressed as a percentage of c.p.e.…”

Repositioned Natural Compounds and Nanoformulations: A Promising Combination to Counteract Cell Damage and Inflammation in Respiratory Viral Infections

“…Apart from marketed drugs, many natural molecules have also been studied to treat or manage symptoms of respiratory viral infections. In recent years, studies describing the positive effects of natural products, mainly extracted from plants, in the treatment and healing of various pathologies have been numerous [ 69 , 70 , 71 , 72 ], and also in the field of virology, several phytochemicals and phytocomplexes have been screened to test their effectiveness [ 73 , 74 , 75 ]. Moreover, compounds of natural origin are very well-placed in the drug repositioning strategy, as they are characterized by unique properties due to their various phytochemical composition to which many pharmacological activities are attributed.…”