Mouthwash Containing The Antiviral Phthalocyanine Derivative Shortens COVID-19 Hospitalizations


In the latest study, Brazilian researchers from the University of São Paulo, Hospital Estadual de Bauru, Instituto de Pesquisa São Leopoldo Mandic and Londrina State University have in a new triple-blind randomized controlled clinical trial found that mouthwashes containing the antiviral phthalocyanine derivative shortens the hospitalization stays of infected COVID-19 patients.
The two-arm study evaluated in vitro the antiviral activity and cytotoxicity of anionic phthalocyanine derivative (APD) in mouthwashes. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19.
All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n = 20) or nonactive mouthwash (control group NAM/n = 21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge.

Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS).

The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity.
Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p = 0.0314).
Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p = 0.0207).
Importantly the study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use ofAPD in a mouthwash as an adjuvant the hospital COVID-19 treatment presented no contraindication and reduced the hospital stay period.
The study findings were published in the peer reviewed journal: Scientific Reports.

Phthalocyanines are analogues of synthetic and aromatic planar porphyrin macrocycles consisting of four indol units linked together by nitrogen atoms18, and have shown good inactivation of various microbial pathogens19.

Furthermore, they are dyes awaiting which, with the combination of a sensitizing drug with visible light, will promote the selective destruction of viruses, bacteria and other microorganisms20.

The potential of phthalocyanines for biological and medical applications has been recognized20,21,22,23, especially in photodynamic therapy, since phthalocyanines in the excited state can promote the reactive oxygen species generation or redox processes, while no such properties are observed in the absence of light.

Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients with SARS-CoV-2 infection14,15.

Hence, the following study aimed to (1) evaluate the antiviral activity and cytotoxicity of APD in vitro and (2) clinically assess the use of an APD-containing mouthwash in hospitalized patients who tested positive for COVID-19 to reduce the severity of the disease and minimize the LOS.


The APD compound was demonstrated to be highly effective in reducing the SARS-CoV-2 viral load in vitro and to exhibit no cytotoxicity in the 1.0 mg/mL to 6.25 × 10–2 mg/mL range. Such a result was also confirmed in a clinical trial where gargling and rinsing five times a day was very helpful in reducing the hospital LOS for patients diagnosed with COVID-19. Further investigation is needed to elucidate this mechanism.


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