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

• Published in: Redox biology 2020-10, Vol.37, p.101734-101734, Article 101734
• Main Authors: Akaberi, Dario, Krambrich, Janina, Ling, Jiaxin, Luni, Chen, Hedenstierna, Göran, Järhult, Josef D., Lennerstrand, Johan, Lundkvist, Åke
• Format: Article
• Language: English
• Subjects: 3CL protease; Animals; Antiviral Agents - pharmacology; Catalytic Domain - drug effects; Chlorocebus aethiops; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - metabolism; COVID-19; COVID-19 Drug Treatment; FRET; Humans; Medicin och hälsovetenskap; Models, Molecular; Nitric oxide; Nitric Oxide - pharmacology; Nitric Oxide Donors - pharmacology; Research Paper; S-Nitroso-N-Acetylpenicillamine - pharmacology; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - enzymology; SARS-CoV-2 - physiology; Vero Cells; Viral Protease Inhibitors - pharmacology; Virus Replication - drug effects
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2020.101734

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. [Display omitted]