Surface Engineering of Graphene through Heterobifunctional Supramolecular-Covalent Scaffolds for Rapid COVID-19 Biomarker Detection.

Graphene is a two-dimensional semiconducting material whose application for diagnostics has been a real game-changer in terms of sensitivity and response time, variables of paramount importance to stop the COVID-19 spreading. Nevertheless, strategies for the modification of docking recognition and antifouling elements to obtain covalent-like stability without the disruption of the graphene band structure are still needed. In this work, we conducted surface engineering of graphene through heterofunctional supramolecular-covalent scaffolds based on vinylsulfonated-polyamines (PA-VS). In these scaffolds, one side binds graphene through multivalent π-π interactions with pyrene groups, and the other side presents vinylsulfonated pending groups that can be used for covalent binding. The construction of PA-VS scaffolds was demonstrated by spectroscopic ellipsometry, Raman spectroscopy, and contact angle measurements. The covalent binding of -SH, -NH2, or -OH groups was confirmed, and it evidenced great chemical versatility. After field-effect studies, we found that the PA-VS-based scaffolds do not disrupt the semiconducting properties of graphene. Moreover, the scaffolds were covalently modified with poly(ethylene glycol) (PEG), which improved the resistance to nonspecific proteins by almost 7-fold compared to the widely used PEG-monopyrene approach. The attachment of recognition elements to PA-VS was optimized for concanavalin A (ConA), a model lectin with a high affinity to glycans. Lastly, the platform was implemented for the rapid, sensitive, and regenerable recognition of SARS-CoV-2 spike protein and human ferritin in lab-made samples. Those two are the target molecules of major importance for the rapid detection and monitoring of COVID-19-positive patients. For that purpose, monoclonal antibodies (mAbs) were bound to the scaffolds, resulting in a surface coverage of 436 ± 30 ng/cm2. KD affinity constants of 48.4 and 2.54 nM were obtained by surface plasmon resonance (SPR) spectroscopy for SARS-CoV-2 spike protein and human ferritin binding on these supramolecular scaffolds, respectively.

Design and synthesis of novel phe-phe hydroxyethylene derivatives as potential coronavirus main protease inhibitors.

In response to the current pandemic caused by the novel SARS-CoV-2, we design new compounds based on Lopinavir structure as an FDA-approved antiviral agent which is currently under more evaluation in clinical trials for COVID-19 patients. This is the first example of the preparation of Lopinavir isosteres from the main core of Lopinavir conducted to various heterocyclic fragments. It is proposed that main protease inhibitors play an important role in the cycle life of coronavirus. Thus, the protease inhibition effect of synthesized compounds was studied by molecular docking method. All of these 10 molecules, showing a good docking score compared. Molecular dynamics (MD) simulations also confirmed the stability of the best-designed compound in Mpro active site.Communicated by Ramaswamy H. Sarma.