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Table 1 Review of in vivo and in vitro studies of the antiviral effect of nitric oxide

From: The potential role of inhaled nitric oxide for postexposure chemoprophylaxis of COVID-19

Reference number in text Virus Type of nitric oxide therapy Study model Main outcome
[4, 5] SARS-CoV NO donor, SNAP In vitro Inhibited SARS CoV replication cycle in a concentration-dependent manner (1)
NO donors, SNAP and SNP In vitro SNAP and SNP inhibited the SARS CoV viral cytopathic effect (2)
[7, 8] SARS-CoV-2 inhaled NO Multicenter randomized controlled trial Ongoing, antiviral effect of high concentrations of inhaled NO administered during early phases of COVID-19 on spontaneous breathing patients, effect on disease progression (3)
Ongoing, testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2) (4)
Single-center, randomized (1:1) controlled, parallel-arm clinical trial Ongoing, prophylactic therapy to reduce the instance of COVID-19 disease in healthcare workers (4)
SNAP In vitro SNAP delayed or completely prevented the development of viral cytopathic effect (5)
[9] Coxsackievirus NO donors SNAP In vitro
Murine model
NO inhibits CVB3 replication by inhibiting protease activity and interrupting the viral life cycle (6)
iNO, SNAP NO inhibits CVB3 replication in part by inhibiting viral RNA and protein synthesis (7)
NO donors
SNAP, PFC, GTN, ISDN)
In vitro NO showed inhibition of the 2A proteinase activity
CVB3-infected mice showed significantly reduced signs of myocarditis after treatment with GTN or ISDN (8)
[10, 11] Influenza Gaseous nitric oxide (gNO) In vitro Viral NA inhibition by gNO was shown and may be responsible for this antiviral effect (9)
SNAP inhibition of influenza virus viral RNA synthesis (10)
[12] Japanese encephalitis virus (JEV) SNAP In vitro NO was found to profoundly inhibit viral RNA synthesis, viral protein accumulation, and virus release from infected cells (11)
MDF to produce NO (inducible NO) In vitro and murine model MDF stimulated macrophages inhibited virus replication with high levels of NO production. MDF treatment increased the survival rate of JEV infected mice (12)
[22] Rhinovirus Nitric oxide donor (NONOate) In vitro (NONOate) inhibited both rhinovirus replication and cytokine production in a dose-dependent fashion without reducing levels of cytokine mRNA (13)
[14] Reovirus iNO In vitro Cytostatic effects antiviral effects e.g. reduction in DNA synthesis, protein synthesis & mitochondrial metabolism (14)
[15] Dengue virus (DENV) SNAP In vitro NO showed an inhibitory effect on viral RNA synthesis. The activity of the viral replicase was suppressed significantly (15)
[16] Herpes simplex virus type 1 (HSV 1) Nitric oxide had inhibitory effects on HSV1 protein and DNA synthesis as well as on cell replication (16)
[17] Porcine circovirus type 2 (PCV2) NO generated from (GSNO) In vivo, in vitro (Murine model) NO strongly inhibited PCV2 replication in vitro. NO reduced the progression of PCV2 infection in mice (17)
[18] Crimean Congo hemorrhagic fever virus (CCHFV) SNAP In vitro NO reduced virion progeny yield with a reduction in expression of viral proteins; the nucleocapsid protein and the glycoprotein, and vRNA (18)
[19] Respiratory Syncytial Virus (RSV) iNO , SNAP In vitro NO has significant direct antiviral activity against RSV, which is more potent with continuous, endogenous NO production than exogenous NO (19)
[13] Human papillomaviruses (HPVs) NVN1000, Topical NO-releasing polymer In vitro NO abrogated HPV-18 progeny virus production. Reduced HPV-18 E6 and E7 oncoproteins. Impaired S-phase progression and induced DNA damage in infected cultures (20)
[20] Vesicular stomatitis virus (VSV) iNO, SNAP In vitro anti-VSV effects of NO in form of significant inhibition of productive VSV infection (21)
[21] Molluscum contagiosum Topical acidified nitrite, nitric oxide liberating cream) A double-blind, group-sequential clinical trial 75% cure rate in the active treatment group
NO is an effective therapy with a 75% cure rate in the treatment group compared to 21% in the control group (22)
topical SB206 (NO releasing topical gel) multicenter, randomized, double-blind, vehicle-controlled clinical trial SB206 is an effective therapy with (SB206 12% / once daily) provided the best balance between MC lesion clearance and tolerability (22)
[6] Hantavirus iNO, SNAP In vitro, murine model NO strongly inhibited hantavirus replication in vitro. The viral titers in iNOS–/– mice were higher compared to the controls, suggesting that NO inhibits hantavirus replication in vivo (23)
  1. Abbreviations: NO nirtic oxide, SNAP S-nitroso-N-acetylpenicillamine, GTN glyceryl trinitrate, ISDN isosorbide dinitrate, PFC: 4-phenyl-3-furoxancarbonitrile, iNO inducible NO, CVB3 coxsackievirus B3, gNO gaseous nitric oxide, NA neuraminidase, JEV Japanese encephalitis virus, MDF macrophage-derived neutrophil chemotactic factor, NONOate 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine, HSV1 herpes simplex virus type 1, DENV dengue virus, PCV2 porcine circovirus type 2, GSNO S-nitrosoglutathione, CCHFV Crimean Congo hemorrhagic fever virus, RSV respiratory syncytial virus, VSV vesicular stomatitis virus