Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
In Vitro study showing that nitric oxide can inhibit the replication of SARS-CoV-2 in Vero E6 cells, and identifying the SARS-CoV-2 main protease as a target for nitric oxide.
Akaberi et al., 31 Oct 2020, Sweden, peer-reviewed, 8 authors.
Contact:
ake.lundkvist@imbim.uu.se.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Redox Biology 37 (2020) 101734
Contents lists available at ScienceDirect
Redox Biology
journal homepage: www.elsevier.com/locate/redox
Research Paper
Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
Dario Akaberi a, Janina Krambrich a, Jiaxin Ling a, Chen Luni b, Göran Hedenstierna c,
Josef D. Järhult d, Johan Lennerstrand e, Åke Lundkvist a, *
a
Department of Medical Biochemistry and Microbiology, Zoonosis Science Center, Uppsala University, Uppsala, Sweden
Department of Microbiology and Tumour and Cell Biology (MTC), Karolinska Institute, Solna, Sweden
c
Department of Medical Sciences, Section of Clinical Physiology, Uppsala University, Uppsala, Sweden
d
Department of Medical Sciences, Zoonosis Science Center, Uppsala University, Uppsala, Sweden
e
Department of Medical Sciences, Section of Clinical Microbiology, Uppsala University, Uppsala, Sweden
b
A R T I C L E I N F O
A B S T R A C T
Keywords:
SARS-CoV-2
COVID-19
Nitric oxide
3CL protease
FRET
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 antimi
crobial 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 Snitroso-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 abol
ished (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.
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