Resorc[4]arene Modifiers for Supramolecular Site-Directed Immobilization of Antibodies on Multi-Walled Carbon Nanotubes.

One of the main problems in developing immunosensors featuring carbon nanotubes (CNTs) is immobilizing antibodies (Abs) onto the CNT surface to afford selective binding to target antigens (Ags). In this work, we developed a practical supramolecular Ab conjugation strategy based on resorc[4]arene modifiers. To improve the Ab orientation on the CNTs surface and optimizing the Ab/Ag interaction, we exploited the host-guest approach by synthesizing two newly resorc[4]arene linkers R1 and R2 via well-established procedures. The upper rim was decorated with eight methoxyl groups to promote selective recognition of the fragment crystallizable (Fc ) region of the Ab. Moreover, the lower rim was functionalized with 3-bromopropyloxy or 3-azidopropiloxy substituents to bind the macrocycles on the multi-walled carbon nanotubes (MWCNTs) surface. Accordingly, several chemical modifications of MWCNTs were evaluated. After the morphological and electrochemical characterization of nanomaterials, the resorc[4]arene-modified MWCNTs were deposited onto a glassy carbon electrode surface to evaluate their potential applicability for label-free immunosensor development. The most promising system showed an improved electrode active area (AEL ) of almost 20 % and a site-oriented immobilization of the SARS-CoV-2 spike protein S1 antibody (Ab-SPS1). The developed immunosensor revealed a good sensitivity (23.64 µA mL ng-1 cm-2 ) towards the SPS1 antigen and a limit of detection (LOD) of 1.01 ng mL-1 .

Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity.

The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have shown that flavonoids, which are small natural molecules, have antiviral activity against coronaviruses (CoVs), including SARS-CoV-2. In this study, we identified the docking sites and binding affinity of several natural compounds, similar to flavonoids, and investigated their inhibitory activity towards 3CLpro enzymatic activity. The selected compounds were then tested in vitro for their cytotoxicity, for antiviral activity against SARS-CoV-2, and the replication of other coronaviruses in different cell lines. Our results showed that Baicalein (100 µg/mL) exerted strong 3CLpro activity inhibition (>90%), whereas Hispidulin and Morin displayed partial inhibition. Moreover, Baicalein, up to 25 µg/mL, hindered >50% of SARS-CoV-2 replication in Vero E6 cultures. Lastly, Baicalein displayed antiviral activity against alphacoronavirus (Feline-CoV) and betacoronavirus (Bovine-CoV and HCoV-OC43) in the cell lines. Our study confirmed the antiviral activity of Baicalein against SARS-CoV-2 and demonstrated clear evidence of its pan-coronaviral activity.