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 |
|---|---|---|---|---|
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) | ||
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) | |||
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] | 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) |