Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro

Abstract

The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations’ health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 μM and 400 μM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.

Therapeutic Potential of Resveratrol in COVID-19-Associated Hemostatic Disorders

“…Interestingly, it was recently proposed that modulating NO levels may be important in preventing, limiting or treating the severe pulmonary consequences of COVID-19 [ 36 ]. This is in accordance with reports showing that, besides its vasodilatorory and anti-inflammatory capacities, NO also has antiviral properties [ 37 ], and can indeed inhibit SARS-CoV-2 replication [ 38 ]. NO synthesis results from the action of three different nitric oxide synthase (NOS) isoforms, and the endothelial nitric oxide synthase (eNOS) is the isoform responsible for NO generation in the vascular endothelium [ 34 ].…”

Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms

“…Most recently, Akaberi et. al [119] demonstrated reduction in SARS-CoV-2 protease activity with up to 99.42% replication inhibition using low doses of SNAP with a SARS-CoV-2 infection model in Vero E6 cells (see Fig. 3 b).…”

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

“…Nitric oxide has general anti-viral actions as well as specific inhibitory effects on coronaviruses. In vitro replication of SARS-CoV-2 was inhibited by treatment of Vero-E6 cells with 200–400 μM of the nitric oxide donor SNAP (S-nitroso-N-acetylpenicillamine) ( 273 ). This effect might be related to the capacity of nitric oxide to promote S-nitrosylation of cysteine groups ( 274 ), a process which inhibits the action of viral proteases ( 275 ).…”

“…This effect might be related to the capacity of nitric oxide to promote S-nitrosylation of cysteine groups ( 274 ), a process which inhibits the action of viral proteases ( 275 ). Indeed, the protease activity of the SARS-CoV-2 3CL cysteine protease was inhibited by ≥100 μM SNAP ( 273 ). Nitric oxide also inhibits replication of SARS-CoV-1 ( 276 ) and does this by two S-nitrosylation-dependent pathways.…”