Efficacy of Sunlight Activated Synthetic Porphyrin in COVID-19 Infected Patients

• Status: Not yet recruiting
• Trial end date: 2020-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Efficacy of Sunlight Activated Synthetic Porphyrin in COVID-19 Infected Patients (SnPPIX)

Mahmoud ELkazzaz(1),Rokia yousry abdelaziz sallam(2)

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Abstract :

The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. Depending on published study in which , conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of specific proteins of the novel coronavirus. The principal investigator demonstrated according to previous researches that some viral structural and nonstructural proteins could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10 and ORF3a proteins coordinated to attack heme on the 1-beta chain of hemoglobin, COVID-19 binds to the porphyrin of haem and displaces iron and a study denonestrated that Covid-19 could cause acquired acute porphyria which is the condition in which there is excess accumulation of porphyrin intermediate metabolites. This point can be taken advantage of X-ray induced visible luminescence of porphyrin for producing of Reactive Oxygen Species (ROS).Many porphyrins are benign in the dark but are transformed by sunlight into caustic, flesh-eating toxins Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells It has been reported that ROS-based inactivation of viruses may occur due to several reasons, such as protein oxidation, single strand breaks in the RNA genome and protein-RNA crosslinking. Since ROS-based inactivation has a multi-targeted mechanism, it is much less likely that a virus would be able to develop resistance against it. Recently, porphyrins, already in use as photosensitizers for Photodynamic Therapy (PDT), were a study target to applications in medical area, namely as possible contrast agents in MRI. could be observed some examples of porphyrin derivatives already study as MRI contrast media. Low dark toxicity, neoplastic tissue affinity and synthetic accessibility are some of the important properties that contribute for its selection. In MRI studies was found that CM based on paramagnetic metalloporphyrins showed higher affinity for neoplastic tissues, observed by increased relaxation time of the neoplastic tissues, which is reflected on an increase in MRI signal and consequently in a better neoplastic lesions detection. A study demonestrated that The sulfonated tetranaphthyl porphyrin contrast agents in MRI (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced HIV infection by 99, 96, 94, and 96%, respectively. Previous studies which showed that Covid -19 binds to the porphyrin of haem and displaces iron in addition to Sulfonated porphyrins and light-stimulated Sn- protoporphyrin IX have broad antiviral activity against more distinct types of viruses, Co-protoporphyrin IX and Sn-protoporphyrin IX inactivate Zika, Chikungunya and other arboviruses by targeting the viral envelope Porphyrins are amphipathic molecules able to interact with membranes and absorb light, being widely used in photodynamic therapy. Previously, we showed that heme, Co-protoporphyrin IX (CoPPIX) and Sn-protoporphyrin IX (SnPPIX) directly inactivate DENV and YFV infectious particles. Here we demonstrate that the antiviral activity of these porphyrins can be broadened to CHIKV, ZIKV, Mayaro virus, Sindb is virus and Vesicular Stomatitis virus. Porphyrin treatment causes viral envelope protein loss, affecting viral morphology, adsorption and entry into target cells , Finally, the principal investigator expect that viral load will be declined with sunlight because In particular, porphyrins absorb essentially all the UV/visible light wavelengths in the emission spectrum of the sun; hence they are active at very low doses .

Keywords: COVID 2019 ,Infection, Sulfonated porphyrins and X-ray induced visible luminescence of porphyrin

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Kafrelsheikh University
• Treatments: Protoporphyrin IX; Tin protoporphyrin IX

Criteria

Inclusion Criteria:

Adult SARI patients with 2019-ncov infection confirmed by PCR; Absolute value of lymphocytes < 0. 6x 109/L; Severe respiratory failure within 48 hours and requires admission to ICU. (severe respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive pressure mechanical ventilation (including non-invasive and invasive mechanical ventilation, PEEP>=5cmH2O))

Exclusion Criteria:

• History of malignancy except carcinoma in situ in the cervix, early stage prostate cancer or non-melanoma skin cancers. Cancer free for less than 5 years.

• Use of investigational drugs or participation in another clinical trial within 30 days or 5 half-lives prior to screening, whichever is longer.

• Serum ferritin > 500 ng/ml or who have received IV iron within 28 days of screening, or currently being treated with oral iron.

• Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.

• Regular use of drugs of abuse and/or positive findings on urinary drug screening.

• Subjects who are severely physically or mentally incapacitated and who, in the opinion of investigator, are unable to perform the subjects' tasks associated with the protocol.

• Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated.

• Subjects with history of photosensitivity or active skin disease, which, in the opinion of the investigator could increase the risk of photosensitivity.

• Subjects with abnormal baseline liver tests or hepatitis serologies that suggest active infection.

• Liver disease

• Renal disease

• Known hypersensitivity or previous anaphylaxis to SnPP and Sulfonated porphyrins