Photoinactivation of Hepatitis A Virus by Synthetic Porphyrins^¶

Abstract

Porphyrins are photosensitizers and may be applicable in situations where viral inactivation is required, as for in vitro inactivation of nonenveloped viruses in blood components or in other aqueous media. No study has examined the efficacy of porphyrin inactivation on human pathogens such as hepatitis A virus (HAV) in plasma or other liquids. Experiments were conducted to evaluate the effect of synthetic porphyrins on HAV in porphyrin‐containing human plasma and phosphatebuffered saline exposed to long‐wavelength (365 nm) UV light. Inactivation of bacteriophage MS2 (MS2) also was determined in some trials. Solutions containing cationic, anionic or amphiphilic porphyrins irradiated with an average light dose of 4.3 J/cm2 for 90 min resulted in >3 log10 (>99.9%) to >4 log10 (>99.99%) inactivation of both HAV and MS2. Viral inactivation may have been greater than observed because the limits of detection of the assay had been reached. Under ambient lighting conditions, none of the porphyrins was mutagenic in the Ames assay and only the congener with the longest chain‐length, tetrakis (N‐[n‐hexadecyl]‐4‐pyridiniumyl) porphyrin, was appreciably toxic to mammalian cells. Disinfection by photoactivated synthetic porphyrins therefore can offer an effective and relatively safe approach to removal of nonenveloped viruses from aqueous media.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…The first report of antiviral PACT using cationic meso-tetrakis (N-methyl-4-pyridiniumyl) porphyrin (TMPyP4) and anionic tetrakis (4-sulfonatophenil) porphyrin (TPPS4) showed an efficient inactivation of non-enveloped MS2 bacteriophage and HAV in PBS solution and plasma. Importantly, none of these compounds were mutagenic, and the activity of cationic compound was much better with regards to the time of light exposure required to achieve significant virus inactivation, and also its activity in the absence light (Casteel et al 2004). The efficiency of TMPyP4 encouraged efforts to develop more effective cationic amphiphilic PS with increased lipophilicity, such as amphiphilic meso-alkylated tetrakis (N-(n-octly)-4-pyridiniumyl) porphyrin (TOcPyP4) and tetrakis (N-(nbutyl)-4-pyridiniumyl) porphyrin (TBuPyP4) and tetrakis (N-(n-hexadecyl)-4-pyridiniumyl) porphyrin (THdPyP4), which showed similar activity against HAV and MS2.…”

“…The efficiency of TMPyP4 encouraged efforts to develop more effective cationic amphiphilic PS with increased lipophilicity, such as amphiphilic meso-alkylated tetrakis (N-(n-octly)-4-pyridiniumyl) porphyrin (TOcPyP4) and tetrakis (N-(nbutyl)-4-pyridiniumyl) porphyrin (TBuPyP4) and tetrakis (N-(n-hexadecyl)-4-pyridiniumyl) porphyrin (THdPyP4), which showed similar activity against HAV and MS2. Photodynamic activity of such PS was, to a certain degree, less efficient in plasma than PBS, which can be explained by affinity to albumin and other plasma proteins that increases with an increase in hydrophobicity of the porphyrin side chain (Casteel et al 2004). Similar to the case for pthalocyanines, the molecular mechanism by which cationic porphyrines inhibit viruses has not received sufficient attention.…”

Porphyrins and Photodynamic Inactivation of Micro-Organisms: A Review

“…Desinfecção por fotoinativação por porrinas sintéticas, portanto, pode oferecer uma abordagem ecaz e relativamente segura para remoção de vírus não envelopados de meios aquosos (CASTEEL et al, 2004).…”

“…O primeiro estudo para examinar a ecácia de porrinas na fotoinativação de patógenos humanos, tais como o vírus da hepatite A (HAV) no plasma e outros líquidos, foi realizado por Casteel et al (2004). O efeito de porrinas sintéticas sobre o HAV e o bacteriófago MS2 em plasma humano foi observado: ocorreu 99,9% de inativação em ambos, HAV e MS2, mostrando que o método pode ser uma abordagem efetiva e segura de remoção de vírus não envelopados em meios aquosos (CASTEEL et al, 2004).…”

“…O efeito de porrinas sintéticas sobre o HAV e o bacteriófago MS2 em plasma humano foi observado: ocorreu 99,9% de inativação em ambos, HAV e MS2, mostrando que o método pode ser uma abordagem efetiva e segura de remoção de vírus não envelopados em meios aquosos (CASTEEL et al, 2004). Marcantonio, Perussi e Perussi (2011) publicaram um estudo relatando que a inativação fotodinâmica tem mostrado diminuição estatisticamente signicante de bactérias periodontopatogênicas e melhoras nos parâmetros clínicos da inamação em paciente com peridontite crônica e agressiva (SCHAWARTZ-FILHO et al, 2009).…”