Anti-Viral Articles:
1 Photodynamic Antimicrobial Chemotherapy (PACT)
Abstract
Whereas the photodynamic therapy (PDT) of cancer has recently shown rapid clinical acceptance, photodynamic antimicrobial chemotherapy (PACT)--which predates the related cancer regimen--is not widely appreciated. Like PDT, PACT utilizes photosensitizers and visible or ultraviolet light in order to give a phototoxic response, normally via oxidative damage. Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are being developed, e.g. in the treatment of oral infection. The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses and parasites. A wide range of photosensitizers, both natural and synthetic, is available with differing physicochemical make-up and light-absorption properties. PACT is proposed as a potential, low-cost approach to the treatment of locally occurring infection
2 Photodynamic Treatment for Viral Infections of the Skin
Effective against human papillomavirus (HPV), Herpes simplex,
Photodynamic therapy (ALA/MAL-PDT) is indicated for the treatment of actinic keratoses, for superficial, nodular basal cell carcinoma and for Bowen's disease; there is evidence that PDT can be active also against bacteria, viruses and fungi. The new indications for PDT include many types of viral skin infections human papillomavirus (HPV)-related as verrucae of feet and hands, Condylomata acuminata, periungual warts, epidermodysplasia verruciformis, but also viral skin lesions non HPV related as molluscum contagiosum and herpes simplex can be successfully treated. The use of PDT in HPV infections is due to its anti-inflammatory and antiproliferative skills: in the lesions treated there is a release of cytotoxic radicals which damage keratinocytes infected by HPV, inducing their selective apoptosis and necrosis. The PDT application in this field of lesions is safe and successful; in comparison with the other techniques it has fewer side-effects and fewer recurrences, but the most important property is that it is not-invasive: it means a reduced risk of infections and excellent cosmetic results.
3 Photodynamic Therapy of Virus-Associated Precancer and Early Stages Cancer of Cervix Uteri
We have analyzed the results of photodynamic therapy using light-sensitizing agent "Photogem" in 72 patients - 56 women with pre-cancerous lesions of cervix and 16 women with early cervical cancer (group 1); Photosens in 47 patients - 35 women with pre-cancerous lesions (CIN III), 12 women with non-invasive cervical cancer (carcinoma in situ) (group 2); and Alasens in 22 patients - 8 women with virus-associated pre-cancerous lesions (high-grade CIN III), 14 with virus-associated early cervical cancer (carcinoma in situ, cervical cancer 1A1) (group 3). The results were as follows: group 1 - complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 50 (89.2%) and 11 (68.8%) cases, significant regression was achieved in 2 cases (3.6%) and in 2 cases (12.5%), stabilization was achieved in 2 cases (3.6%) and in 2 cases (12.5%), progression was achieved in 2 cases (3.6%) and in 1 case (6.2%) accordingly. In the group of patients after PDT using Photosens complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 33 cases (94.2%) and in 10 cases (83.4%) cases, significant regression was achieved in 1 case (2.9%) and in 1 case (8.3%), stabilization was achieved in 1 cases (2.9%) and in 1 cases (8.3%). In the group of women after surgical treatment anti-viral efficacy was assessed. It s necessary to note that not a single relapse was observed. Anti-viral effect was registered in 49 (90.4%) cases The longest HPV-free period that we observed was 5 years. 12 women with CIN III and 4 women with carcinoma in situ became pregnant.
4 Dual Activity of Amphiphilic Zn(II) Nitroporphyrin Derivatives as HIV-1 Entry Inhibitors and in Cancer Photodynamic Therapy
Abstract
Two Zn(II) nitro porphyrin derivatives bearing combinations of meso-4-nitrophenyl and meso-4-methylpyridinium moieties and their free-base precursors were synthesized through one-pot microwave process, purified and characterized. The biological activity of these nitroporphyrins was assessed under both photodynamic and non-photodynamic conditions to correlate their structure-activity relationship (SAR). Unlike, the free-base precursors, Zn(II) complexes of these nitroporphyrins displayed nearly complete inhibition in the entry of lentiviruses such as HIV-1 and SIVmac under non-photodynamic conditions. In addition, the Zn(II) complexes also exhibited a higher in vitro photodynamic activity towards human lung cancer cell-line A549 than their free-base precursors. Our results strongly suggest that incorporation of Zn(II) has improved the antiviral and anticancer properties of the nitroporphyrins. To the best of our knowledge, this is the first report demonstrating the dual activity of nitroporphyrin-zinc complexes as antiviral and anti-cancer, which will aid in their development as therapeutics in clinics.
5 Photoinactivation of Cell-Free Human Immunodeficiency Virus by Hematoporphyrin Monomethyl Ether
Abstract
Human immunodeficiency virus (HIV) particles that remain in the blood of patients are frequently ignored as targets for AIDS treatment. We therefore investigated the use of photodynamic therapy (PDT) with hematoporphyrin monomethyl ether (HMME) as a means of inactivating cell-free HIV in vitro. Virus particles including HIV-1(IIIB), resistant HIV-1 variants, HIV-1 clinical variants, and HIV-2 variants were incubated with HMME for 40 min, followed by irradiation with a 630-nm semiconductor laser at an energy density of 0.3 J/cm(2). The antiviral effects were evaluated by counting syncytium formation or measuring p24 antigen expression levels in supernatants by enzyme-linked immunosorbent assay. The relationships between photoinactivation and HMME concentrations, energy density, power density and antioxidants (NaN(3) and D: -mannitol) were also assessed using the above methods. All the tested virus particles were completely responsive to HMME-PDT. HMME concentration and energy density were positively correlated with photoinactivation of HIV, while power density was negatively correlated. Both sodium azide and D: -mannitol weakened the inhibitory effect of PDT on virus-induced membrane fusion, with D: -mannitol having a stronger effect. HMME-PDT can inactivate HIV particles, and may therefore represent a promising treatment for AIDS patients
6 Photodynamic Inactivation of Herpes Simplex Viruses
Abstract
Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract OrthoquinTM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.
7 Topical Photodynamic Therapy With 5-aminolevulinic Acid for Cervical High-Risk HPV Infection
Abstract
Objective: To investigate the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for cervical high-risk HPV (HR-HPV) infection.Methods: In this prospective study, a total of 76 patients with persistent cervical HR-HPV infection were randomly divided into two groups. The treatment group (39 patients) received three treatments of ALA-PDT at two-week intervals. The control group (37 patients) received no treatment. All patients were followed up for 9 months. Hybrid Capture HPV DNA Assay and ThinPrep cytology test (TCT) were performed for both groups. Patients with abnormal TCT results received colposcopic biopsy before treatment and during follow-ups.Results: HR-HPV remission rates were 64.10% (25/39) in the treatment group and 24.32% (9/37) in the control group at 3 month follow-up. Complete remission rates were 76.92% (30/39) and 32.40% (12/37), respectively, in the two groups at 9 month follow-up. There was a statistically significant difference between the two groups (P<0.01). Conversion rates of abnormal TCT results were 81.81% (9/11) in the treatment group and 12.50% (1/8) in the control group at 3 months, and 90.90% (10/11) and 25.00% (2/8), respectively, at 9 months. Five of six patients with CIN I in the treatment group and no patients in the control group achieved complete response at 9 months. There was a statistically significant difference between the two groups (P<0.01).Conclusion: Topical ALA-PDT is an effective, safe and well tolerated treatment for cervical HR-HPV infection
8 Topical 5-aminolevulinic Acid Photodynamic Therapy for Laryngeal Papillomatosistosis Treatment
Abstract
Background: To explore the therapeutic effect of topical 5-Aminolevulinic Acid photodynamic therapy (ALA-PDT) on laryngeal papillomatosis (LP) treatment.
Methods: 13 patients with LP underwent topical ALA-PDT after tumor resection (CO2laser or/and microdebrider resection). All patients were irradiated 3-4 times. After ALA-PDT treatment, the laryngoscopic examination was performed every 1-2 months to observe the therapeutic effect.
Results: All 13 patients were followed up for more than 1 year. Eleven cases (84.6%) showed no recurrence; two cases (15.4%) had relapses. One child developed III° inspiratory dyspnea caused by laryngeal mucosal edema and need endotracheal intubation again. Four patients had adhesion of the anterior commissure of the vocal cord. The detection rate of HPV infections was 76.9% and two patients had multiple HPV subtype co-infection.
Conclusions: The preliminary effect of topical ALA-PDT significantly reduces recurrence and improves the cure rate of LP. Further research on this treatment is still required.
Keywords: Human papillomavirus; Laryngeal papillomatosis; Photodynamic therapy; Recurrence; Viral infection.
9 Treatment of HPV Infection-Associated Cervical Condylomata Acuminata With 5-aminolevulinic Acid-Mediated Photodynamic Therapy
Abstract
The aim of this study was to investigate the efficacy of 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) in treatment of human papillomavirus (HPV)-associated cervical condylomata. A total of 56 patients with cervical and external condylomata lesions were recruited for this open-label study. HPV genotyping of exfoliated cells collected from the cervix and external lesions was performed. Cervical lesions were treated with PDT by applying ALA gel (10%) to the surface of the cervix for 4 h followed by irradiating with a 635 nm laser at 100 J cm(-2). PDT was repeated at 2-week intervals if lesion and HPV infection remained. Patients were followed up for 6-24 months. Genotyping analysis revealed four HPV subtypes (HPV6, 11, 16 and 18). The overall complete remission rate of 1-4 sessions of treatments was 98.2% and the corresponding HPV clearance rate was 83.9%. Ten cases showed complete removal of cervical lesions and HPV infection after a single treatment. Recurrence rate was 3.6%. Adverse effects were minimal and no structural complications were reported. In conclusion, topical ALA PDT is safe and effective for eradicating cervical HPV infection and eliminating condylomata lesion. Its definitive role in treating cervical condylomata deserves further investigation.
10 Antifungal and Antibacterial Activities of a BODIPY-Based Photosensitizer
Abstract
Antimicrobial photodynamic inactivation (aPDI) employing the BODIPY-based photosensitizer 2,6-diiodo-1,3,5,7-tetramethyl-8-(N-methyl-4-pyridyl)-4,4'-difluoro-boradiazaindacene (DIMPy-BODIPY) was explored in an in vitro assay against six species of bacteria (eight total strains), three species of yeast, and three viruses as a complementary approach to their current drug-based or non-existent treatments. Our best results achieved a noteworthy 5-6 log unit reduction in CFU at 0.1 μM for Staphylococcus aureus (ATCC-2913), methicillin-resistant S. aureus (ATCC-44), and vancomycin-resistant Enterococcus faecium (ATCC-2320), a 4-5 log unit reduction for Acinetobacter baumannii ATCC-19606 (0.25 μM), multidrug resistant A. baumannii ATCC-1605 (0.1 μM), Pseudomonas aeruginosa ATCC-97 (0.5 μM), and Klebsiella pneumoniae ATCC-2146 (1 μM), and a 3 log unit reduction for Mycobacterium smegmatis mc2155 (ATCC-700084). A 5 log unit reduction in CFU was observed for Candida albicans ATCC-90028 (1 μM) and Cryptococcus neoformans ATCC-64538 (0.5 μM), and a 3 log unit reduction was noted for Candida glabrata ATCC-15545 (1 μM). Infectivity was reduced by 6 log units in dengue 1 (0.1 μM), by 5 log units (0.5 μM) in vesicular stomatitis virus, and by 2 log units (5 μM) in human adenovirus-5. Overall, the results demonstrate that DIMPy-BODIPY exhibits antiviral, antibacterial and antifungal photodynamic inactivation at nanomolar concentrations and short illumination times.
11 Novel Phthalocyanines Activated by Dim Light for Mosquito Larva- And Cell-Inactivation With Inference for Their Potential as Broad-Spectrum Photodynamic Insecticides
Abstract
Mosquitoes are significant vectors, responsible for transmitting serious infectious diseases, including the recent epidemics of global significance caused by, for example, Zika, Dengue and Chikungunya viruses. The chemical insecticides in use for mosquito control are toxic and ineffective due to the development of resistance to them. The new approach to reduce mosquito population by releasing genetically modified males to cause female infertility is still under environmental safety evaluation. Photodynamic insecticides (PDI) have long been known as a safe and effective alternative by using dyes as the photosensitizers (PS) for activation with light to generate insecticidal singlet oxygen and reactive oxygen species. This approach warrants re-examination with advances in the chemical synthesis of novel PS, e.g. phthalocyanines (PC). Nine PC were compared with five porphyrin derivatives and two classic PS of halogenated fluoresceins, i.e. cyanosine and rose bengal experimentally for photodynamic treatment (PDT) of the larvae of laboratory-reared Aedes mosquitoes and their cell lines. Groups of 2nd instar larvae were first exposed overnight to graded concentrations of each PS in the dark followed by their exposure to dim light for up to 7 hours. Larvae of both experimental and control groups were examined hourly for viability based on their motility. Monolayers of mosquito cells were similarly PS-sensitized and exposed briefly to light at the PS-specific excitation wavelengths. Cell viability was assessed by MTT reduction assays. Of the 16 PS examined for photodynamic inactivation of the mosquito larvae, effective are three novel PC, i.e. amino-Si-PC1 and -PC2, anilinium Zn-PC3.4, pyridyloxy Si-PC14 and two porphyrin derivatives, i.e. TPPS2 and TMAP. Their EC50 values were determined, all falling in the nanomolar range lower than those of rose bengal and cyanosine. All PS effective in vivo were also found to dose-dependently inactivate mosquito cells photodynamically in vitro, providing cellular basis for their larvicidal activities. The present findings of novel PC with effective photodynamic larvicidal activities provide fresh impetus to the development of PDI with their established advantages in safety and efficacy. Toward that end, the insect cell lines are of value for rapid screening of new PC. The optimal excitability of PC with insect-invisible red light is inferred to have the potential to broaden the range of targetable insect pests.
12 Light-activated Nanotube-Porphyrin Conjugates as Effective Antiviral Agents
Abstract
Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex vivo reusable antiviral agents.
13 In light of the overwhelming evidence of PACT technology as a "Broad Spectrum Anti-Viral"... NO published articles using PACT against these deadly viruses that pose the threat of a Pandemic that would dwarf the "COVID-10 in severity are available on PubMed as shown below!
