Tuning riboflavin derivatives for photodynamic inactivation of pathogens

Abstract

The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin’s visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives’ toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.

Effect of Chitosan–Riboflavin Bioconjugate on Green Mold Caused by Penicillium digitatum in Lemon Fruit

“…For alternative irradiation durations (15 or 30 min), an improvement in control is not consistently observed. The observed variations in the latter results can be attributed to the following: (i) prolonged LED light exposure, resulting in faster riboflavin photodecomposition [31], and consequently, the efficacy diminishes over time; (ii) in the fruits where CH-RF was applied without initial LED light exposure, they were kept in a natural-light environment in the laboratory, rather than complete darkness. This result suggests the possibility of some activation of riboflavin taking place.…”

Photodynamic Inactivation of SARS-CoV-2 Infectivity and Antiviral Treatment Effects In Vitro

“…Since SARS-CoV-2 requires an envelope homotrimeric spike glycoprotein (S) to interact with the cellular receptor ACE-2 [36], it was proposed that selective impairment of surface proteins, like spike glycoprotein (S), by PDI can effectively inhibit infectivity of SARS-CoV-2 [24,25,37]. Additionally, it was suggested that effectivity of antiviral PDI may, in part, be explained by a light-induced photocleavage reaction of viral ssRNA [38]. However, this occurs by light irradiation with much shorter wavelengths (345-420 nm).…”

“…Most of these reports focus on the use of methylene blue or curcumin, requiring blue light for activation, which may pose significant risks and does not penetrate into deeper tissues. Often, surrogates (like Phage Phi6 [42] or HIV-based pseudotyped models [43], lentiviruses pseudotyped with the SARS-CoV-2 Spike [44], murine hepatitis virus [38], alphacoronavirus HCoV-229E or the betacoronavirus HCoV-OC43 [44]) were used instead of SARS-CoV-2 isolates.…”

Riboflavin and Its Derivates as Potential Photosensitizers in the Photodynamic Treatment of Skin Cancers

“…Interestingly, lumichrome, the product of light-induced or enzymatic degradation of riboflavin, appeared to be selective towards bacteria, being ten times more effective against Gram-positive bacteria than against Gram-negative bacteria [ 87 ]. Recently, Crocker et al [ 98 ] showed that the use of LED light (1 × 10 5 lux) and flavin with a bromine atom in the structure, increases the production of singlet oxygen through a heavy-atom effect, resulting in an increased PDT effect against both bacteria and viruses. This inspiring research may result in the design of a new generation of flavins.…”