Studies on Antifungal Properties of Methacrylamido Propyl Trimethyl Ammonium Chloride Polycations and Their Toxicity In Vitro.

The biological activity of polycations is usually associated with their biocidal properties. Their antibacterial features are well known, but in this work, observations on the antifungal properties of macromolecules obtained by methacrylamido propyl trimethyl ammonium chloride (MAPTAC) polymerization are presented. The results, not previously reported, make it possible to correlate antifungal properties directly with the structure of the macromolecule, in particular the molecular mass. The polymers described here have antifungal activity against some filamentous fungi. The strongest effect occurs for polymers with a mass of about 0.5 mDa which have confirmed activity against the multidrug-resistant species Scopulariopsis brevicaulis, Fusarium oxysporum, and Fusarium solani, as well as the dermatophytes Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton interdigitale, and Trichophyton tonsurans. In addition, this publication describes the effects of these macromolecular systems on serum and blood components and provides a preliminary assessment of toxicity on cell lines of skin-forming cells, i.e., fibroblasts and keratinocytes. Additionally, using a Franz diffusion chamber, a negligibly low transport of the active polymer through the skin was demonstrated, which is a desirable effect for externally applied antifungal drugs. IMPORTANCE Infectious diseases are a very big medical, social, and economic problem. Even before the COVID-19 pandemic, certain infections were among of the most common causes of death. The difficulties in the treatment of infectious diseases concern in particular fungal diseases, against which we have only a few classes of drugs represented by a few substances. The publication presents the preliminary results of the in vitro antifungal activity studies of four MAPTAC polymers on different fungal species and their cytotoxicity to human cells (fibroblasts and keratinocytes). The paper also compares these properties with analogous ones of two commonly used antifungal drugs, ciclopirox and terbinafine.

HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV.

Among seven coronaviruses that infect humans, three (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of human coronavirus NL63 (HCoV-NL63). Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low-pathogenicity human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo models of human airway epithelia, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry into the host cell by interaction with the S protein.IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of an HTCC compound, previously developed by us, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses-SARS-CoV-2 and MERS-CoV.