Common oral fertilizers have been found to inhibit SARS-CoV-2 in vitro

The researchers found that cetylpyridinium chloride, found in most oral forms, reduces the incidence of severe respiratory coronavirus syndrome 2 (SARS-CoV-2). in vitro, likely to inhibit viral fusion with target cells. With more tests to prove its validity, oral transfusion could be a simple, inexpensive way to prevent transmission.

Study: Orally infected Cetylpyridinium chloride reduces SARS-CoV-2 in vitro infection.  Image credit: Ju Jae-young / Shutterstock

Past studies have shown that oral contraceptives can have antiviral properties. They can reduce respiratory tract coronavirus infections, including influenza virus infections and coronavirus acute respiratory syndrome 2 (SARS-CoV-2), the causative agent of the conventional coronavirus disease 2019 ( COVID-19).

If more experiments confirm oral antiviral properties, they could be a robust and economical strategy to combat the pandemic. Oral use would be a cheap and accessible strategy that can be implemented quickly. Reducing viral loads in the mouth can help reduce the transmission chain. Mouthwashes are also made as oral sparks, so they can be easily used by the elderly.

Although studies have reported in vitro antiviral activity of various oral products, it is not known which parts in the oral cavity are responsible for the antiviral activity and their mode of action.

Understanding the effect of oral contraceptives on SARS-CoV-2 infection

In a new study published in the bioRxiv * preprint server, researchers report the effects of cetylpyridinium chloride (CPC) used in large amounts of oral and shower. CPC is a square ammonium mixture with antiseptic and antimicrobial activity.

The authors tested the ability of oral with CPC to inhibit SARS-CoV-2 into cells. They used HEK293T cells expressing the angiotensin-converting enzyme receptor 2 (ACE2) as target cells and pseudotyped lentivirus expressing SARS-CoV-2 spike protein. A luciferase-based assay allowed them to detect viral attachment to the target cells.

The pseudovirus was mixed with various oral extracts and added to the target cells. The authors tested two mouthpieces from Dentaid: Perio Aid Intensive Care and Vitis CPC Protec. To control cytotoxicity, the authors also mixed orally with the target cells without the pseudovirus. In addition, they used the same oral format but without CPC as a control.

They found that the oral contraceptives inhibited viral fusion to host cells, with their inhibitory activity increasing with increased oral concentrations. They did not see any inhibition using oral formulation without CPC, suggesting that the antiviral activity is due to CPC. In addition, the researchers inhibited CPC in water and found that this inhibition also inhibited the entry of virus into the target cells.

The team also isolated SARS-CoV-2 from a clinical sample collected from an 89-year-old male patient. They added the same level of the virus and oral CPC or CPC and mixed them.

They found that a high dose of CPC was effective in reducing virus infection on Vero E6 cells. 2-minute treatment with oral CPC reduced Fine Culture infectious dose by 50% (TCID)50) / ml 1000 times. The formulas without CPC had no effect on virus infection. The doses of CPC that inhibited viral fusion to the host cell were not toxic to the host cells.

Cetylpyridinium chloride reduces SARS-CoV-2 infectivity

The antiviral activity of CPC appears to arise from its ability to inhibit the viral envelope, similar to that previously observed for influenza virus. Thus, oral administration with CPC may protect against oral mucus infection.

However, since SARS-CoV-2 mainly enters host through the upper respiratory tract, nasal sprays containing CPC may be more effective in preventing or reducing infection.

The experiments performed by the authors used an infectious viral stock, but the virus present may have a lower susceptibility to around 1–2 ml. Oral rinses are usually made with about 10 ml of oral, so the ratio of CPC to virus is more similar compared to those used in laboratory tests, the The authors believe that it may be more effective in the mouth than in the in vitro tests.

Oral antiviral activity in which CPC inhibits SARS-CoV-2 inhibition.  Percentage inhibition of viral entry of HEK-293T target cells expressing ACE2 exposed to a fixed concentration of SARS-CoV-2 in the presence of increasing concentrations of oral forms (A and C), their vehicles (B and D) and CPC attenuated into water (E).  Nonlinearity responds to a variable response curve from a single experiment with two replicas shown (red lines), without data from drug collections with associated toxicity.  When measured, the unique IC50 value of the graph is indicated.  Cytotoxic effects on HEK-293T cells expressing ACE2 cells exposed to larger clusters of oral or non-viral vehicles are also shown (gray lines).

Oral antiviral activity in which CPC inhibits SARS-CoV-2 ingestion. Percentage inhibition of viral entry of HEK-293T target cells expressing ACE2 exposed to a fixed concentration of SARS-CoV-2 in the presence of increased concentrations of oral forms (A and C), their vehicles (B and D) and CPC are attenuated into water (E). Nonlinearity responds to a variable response curve from a single experiment with two replicas shown (red lines), without data from drug collections with associated toxicity. When measured, the unique IC50 value of the graph is indicated. Cytotoxic effects on HEK-293T cells expressing ACE2 cells exposed to larger clusters of oral or non-viral vehicles are also shown (gray lines).

“Thus, oral contraceptives containing CPC may be a cost-effective measure to reduce SARS-CoV-2 infection in saliva, helping to reduce viral transmission from infected people. , ”Wrote the authors. The spread of a virus has been seen when infected people talk, shout, or sing; susceptible virus was obtained from the saliva of infected people.

The authors write that future work should investigate whether oral with CPC can reduce viral loads and infectivity in the mouths of infected people. In addition, more work is needed to understand how long the antiviral activity of oral CPC lasts. All of this will help us understand how to use oral as a cheap measure to reduce SARS-CoV-2 infection in the saliva.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.

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