key: cord-0837362-c5aacnb7 authors: Law, Siukan; Lo, Chuiman; Han, Jie; Leung, Albert Wingnang; Xu, Chuanshan title: Antimicrobial Photodynamic Therapy with Hypocrellin B against SARS-CoV-2 infection? date: 2021-04-20 journal: Photodiagnosis Photodyn Ther DOI: 10.1016/j.pdpdt.2021.102297 sha: 9d93cad3255b0a5428e19c6f30ff00a2b548c320 doc_id: 837362 cord_uid: c5aacnb7 nan Up to the present, the COVID-19 outbreak has occurred since more than a year. We still do not have an effective therapy to combat SARS-CoV-2 except vaccination. Antimicrobia l photodynamic therapy (aPDT) might be a good choice for the prevention and treatment of SARS-CoV-2 because it only targets the infection area using photosensitizers with a specific wavelength. "Hypocrellin B" is a substance used traditionally in Chinese medicine and as a photosensitizer which is used in China to treat many diseases for a long time. Its photodynamic action and research progress of "hypocrellin B" will be discussed. Why do we apply the PDT with "hypocrellin B" as a photosensitizer against SARS-CoV-2? Is this a possible choice for the treatment of patients with SARS-CoV-2? Hypocrellin B (HB) is a natural pigment of perylquinone derivatives isolated from the traditional Chinese herb Hypocrella bambuase [1] . It has significant anti-tumor and anti-viral properties as well as a strong photodynamic effect on the malignant tumor, and human immunodeficiency virus type I (HIV-I) [2] . In general, HB consists of aromatic rings, phenolic hydroxyl groups, carbonyl groups, siderings, and methoxyl groups ( Figure. 1 ). It has two major fluorescence peaks including the neutral mono-molecule at ~610 nm, an excited proton at ~660 nm, and the zwitterions between ~610 nm to 660 nm because the perylene quinonoid pigments have three visible bands start from the transition of π-π * conjugated systems and intramolecular proton transfer [3] . HB activated upon interaction with a specific wavelength of light selectively initiate necrosis and apoptosis to the target cells or specific area. HB is non-toxic in dark and could be absorbed by cells within the body but it would be gone in normal and healthy cells after 1 to 3 days [5] . PDT causes acute inflammation leading to immune stimulation and increasing the number of antigens to T cells in an immune system [6] . Hypocrellin-mediated PDT has been an approved and effective treatment for esophageal cancer, nasopharyngeal cancer, lung cancer, and ovarian cancer which re-established the chemosensitivity and radiosensitivity of human cells as hypocrellin contributed to the phototoxicity of cells [7] . In also identified the effect of HB-PDT on apoptosis, adhesion, and migration of cancer cells in vitro. They found that HB-PDT increased the early apoptotic and late apoptotic (necrotic) rates to 16.40% and 24.67% respectively, and inhibited adhesion and migration of human ovarian cancer HO-8910 cells [11] . These results proved that the singlet oxygen ( 1 O 2 ) and superoxide (O 2 -) were the activated reactive oxygen species (ROS) for cell death induced by hypocrellins photosensitization [12] . Emerging evidence had shown that nano-system combined with hypocrellins B could significantly improve their solubility, bioavailability, and enhance their photodynamic efficacy [19] . It was an efficient therapy to decrease the microbial load (viral and bacterial) in the respiratory tract through the generation of ROS to promote the damage of viruses targets such as nucleic acids (DNA or RNA) [20] . J o u r n a l P r e -p r o o f The above information suggests that HB is a possible candidate as a photosensitizer in the application of PDT for the treatment of SARS-CoV-2. Growing evidence has shown that HB is a non-toxic and natural photosensitizer. HB-mediated PDT has been studied in esophageal cancer, nasopharyngeal cancer, lung cancer, and ovarian cancer. Its photosensitization is similar to the porphyrin or methylene blue via ROS to decrease the loading of SARS-CoV-2 and destroy the SARS-CoV-2 binding on the protein-membrane of an upper respiratory tract. Meanwhile, HB might be further developed into a nano-system to get a better PDT efficacy and improve its solubility and bioavailability. However, much more works need to be done in the human clinical trials of HB-aPDT on SARS-CoV-2. Hypocrellin Hypocrella bambuase, is phototoxic to human immunodeficiency virus Antimicrobial and antileishmanial activities of hypocrellins A and B The effects of environments on the fluorescence spectra of hypocrellin A and B Hypocrellins and their use in photosensitizat ion Photodynamic therapymechanisms, photosensitizers and combinations Photodynamic therapy and anti-tumour immunity Photodynamic therapy for cancer: Role of natural products Comparative study on the killing effect between hypocrellins Bphotodynamic therapy and hematoporphyrin derivative-photodynamic therapy on human lung cancer cells Comparative Study on Killing Effect to Esophageal Cancer Cell Line between Hypocrellins B-photodynamic Therapy and Hematoporphyrin derivative-photodynamic Therapy Apoptosis of breast cancer cells induced by hypocrellin B under light-emitting diode irradiation Effect of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor Characterization of biodegradable poly (D, L-lactide-co-glycolide) nanoparticles loaded with bacteriochlorophyll-a for photodynamic therapy Photodynamic action of LED activated nanoscale photosensitizer in nasopharyngeal carcinoma cells Enhanced effect of photodynamic therapy in ovarian cancer using a nanoparticle drug delivery system Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles Photodynamic therapy for COVID-19 Does PDT have potential in the treatment of COVID 19 patients? Photodiagnosis and photodynamic therapy COVID-19: Beyond the virus. The use of photodynamic therapy for the treatment of infections in the respiratory tract Trends and targets in antiviral phototherapy The authors received no funding source/grants or other materials support for this work. The authors have no conflicts of interest to disclose.