A recent study published in the journal ACS Biomaterials Science & Engineering examines the biodistribution and safety of SBCoV207, a novel nanoligomer that was used to target miR-2392 in a murine model.
The advent and global spread of the severe acute respiratory syndrome coronavirus 2 made it clear that there are no antiviral medicines for respiratory infections (SARS-CoV-2). In the study, surface plasmon resonance (SPR) measurements were performed after designing and synthesising nanoligomers.
In Vero E6 cells, SARS-CoV-2 was multiplied, and virus titers were assessed using the plaque test. This was followed by an immunofluorescence assay for the viral nucleocapsid (N) protein and a quantitative reverse-transcription polymerase chain reaction (PCR) assay for the quantification of SARS-CoV-2 RNA levels.
Female BALB/c mice aged eight to twelve weeks were used in a five-day intranasal safety trial. Each group received intranasal administration of SBCoV207 dosages of 1, 2, 5, or 10 mg/kg, and they were observed for five days before being put to death.
Prior to euthanasia, blood and urine samples were taken, and tissue samples came next. Tumor necrosis factor-alpha (TNF-alpha), albumin, and interleukin-6 serum levels were measured using the enzyme-linked immunosorbent test (ELISA) (IL-6). On mice that were given either 10 mg/kg of SBCoV207 or the control therapy, a histological examination of the spleen, lungs, kidneys, and liver was done.
Blood and urine samples that were taken before to euthanasia at one, three, six, or 24 hours following SBCoV207 injection were used in a 24-hour intranasal biodistribution investigation. After that, research on the safety and biodistribution of the drug were carried out intravenously and intraperitoneally. The SBCoV207 concentrations in various organ tissues were then determined.
When compared to missense nanoligomers, SBCoV207 was found to limit viral infection and result in a ten-fold decrease in viral messenger RNA (mRNA) levels. Compared to missense nanoligomers, SBCoV207 exhibited high binding to the miR2392 binding sequence, according to SPR assays. After receiving SBCoV207, none of the mice’s weights changed, and they all carried on eating and drinking normally.
Both animals treated with SBCoV207 and control mice showed subacute hepatic inflammation and alveolar haemorrhage, according to histological examinations. Both the treated and control mice had normal levels of albumin, TNF, and IL-6. Even 24 hours after the injection of SBCoV207, the majority of chemokine and cytokine levels were below the limit of detection (LOD).
The kidneys, urine, lungs, and whole blood contained the highest concentrations of nanoligomers. Regardless of the mode of administration, SBCoV207 was removed through urine excretion within a few hours and showed no accumulation in organs by five days. Notably, from one hour to five days after delivery, no toxicity was seen at any point.
The intraperitoneal and intravenous methods were used to deliver SBCoV207 to the spleen and liver at steady-state concentrations. After five days, SBCoV207 concentrations of 500–700 ng/g tissue were found in the liver, urine, and spleen, with much lower levels seen in other organ tissues. Additionally, five days after injection, one mouse had high levels of SBCoV207 in the kidney and two mice had high levels in the lungs.
No toxicity was observed in mice treated with the nanoligomer SBCoV207, regardless of the route of administration, according to the results of the current investigation. High biodistribution of SBCoV207 was seen in the lungs and infection site, while little accumulation of the virus was seen in the organs.
When used in combination, nanoligomer therapy holds promise for treating severe COVID-19, particularly in regions with low immunisation rates or where novel variations have been discovered. This method may also assist develop a plan for preventing upcoming pandemics.