Graphene Oxide Nanosheets Interact and Interfere with SARS‐CoV‐2 Surface Proteins and Cell Receptors to Inhibit Infectivity

From Wiley via Jisc Publications RouterHistory: received 2021-03-13, pub-electronic 2021-05-14Article version: VoRPublication status: PublishedFunder: University of PaduaFunder: UKRI EPSRC; Grant(s): EP/P00119X/1Funder: Turkish Academy of Sciences (TUBA)Funder: Scientific and Technology Council of Turkey; Grant(s): 18AG020Funder: Türkiye Bilimler Akademisi; Id: http://dx.doi.org/10.13039/501100004412; Grant(s): GEBIP 2018Funder: Türkiye Bilimsel ve Teknolojik Araştirma Kurumu; Id: http://dx.doi.org/10.13039/501100004410; Grant(s): 18AG020Funder: Engineering and Physical Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000266; Grant(s): EP/P00119X/1Abstract: Nanotechnology can offer a number of options against coronavirus disease 2019 (COVID‐19) acting both extracellularly and intracellularly to the host cells. Here, the aim is to explore graphene oxide (GO), the most studied 2D nanomaterial in biomedical applications, as a nanoscale platform for interaction with SARS‐CoV‐2. Molecular docking analyses of GO sheets on interaction with three different structures: SARS‐CoV‐2 viral spike (open state – 6VYB or closed state – 6VXX), ACE2 (1R42), and the ACE2‐bound spike complex (6M0J) are performed. GO shows high affinity for the surface of all three structures (6M0J, 6VYB and 6VXX). When binding affinities and involved bonding types are compared, GO interacts more strongly with the spike or ACE2, compared to 6M0J. Infection experiments using infectious viral particles from four different clades as classified by Global Initiative on Sharing all Influenza Data (GISAID), are performed for validation purposes. Thin, biological‐grade GO nanoscale (few hundred nanometers in lateral dimension) sheets are able to significantly reduce copies for three different viral clades. This data has demonstrated that GO sheets have the capacity to interact with SARS‐CoV‐2 surface components and disrupt infectivity even in the presence of any mutations on the viral spike. GO nanosheets are proposed to be further explored as a nanoscale platform for development of antiviral strategies against COVID‐19

Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 In Vitro

Ribavirin is a guanosine analog and has a broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that Ribarivin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, Ribavirin was shown to decrease the expression of TMPRSS2 both at mRNA and protein levels 48 hours after treatment. The suppressive effect of Ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that Ribavirin also showed an inhibitory effect on TMPRSS2 enzyme. Based on these results, we hypothesized that Ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, Ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effect of TMPRSS2 and ACE2 expression.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Small Warriors of Nature: Novel Red Emissive Chlorophyllin Carbon Dots Harnessing Fenton‐Fueled Ferroptosis for In Vitro and In Vivo Cancer Treatment

Abstract The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin‐based carbon dots (Chl‐D CDs) are successfully synthesized. Chl‐D CDs exhibit unique spectroscopic traits and are found to induce a Fenton‐like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl‐D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl‐D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl‐D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl‐D CDs' anticancer activity. Notably, the Chl‐D CDs' capacity to trigger a Fenton‐like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl‐CDs can lead to a secure and efficient combined cancer therapy