The applicability of G-quadruplexes (G4s) as antiviral targets, therapeutic agents and diagnostic tools for coronavirus disease 2019 (COVID-19) is currently being evaluated, which has drawn the extensive attention of the scientific community. During the COVID-19 pandemic, research in this field is rapidly accumulating. In this review, we summarize the latest achievements and breakthroughs in the use of G4s as antiviral targets, therapeutic agents and diagnostic tools for COVID-19, particularly using G4 ligands. Finally, strength and weakness regarding G4s in anti-SARS-CoV-2 field are highlighted for prospective future projects.

Isonitrile group has been identified in many natural products. Due to the broad reactivity of N≡C triple bond, these natural products have valuable pharmaceutical potentials. This review summarizes the current biosynthetic pathways and the corresponding enzymes that are responsible for isonitrile-containing natural product generation. Based on the strategies utilized, two fundamentally distinctive approaches are discussed. In addition, recent progress in elucidating isonitrile group formation mechanisms is also presented.

Porphyrins have been widely used in the self-assembly of metallo-supramolecules. In this study, we introduced 2,2':6,2"-terpyridine (tpy) into a porphyrin core to synthesize a tetratopic building block with multiple conformers. During the self-assembly with Zn(II), such a mixture of conformers was able to form a discrete nanoprism with all building blocks in one conformation. Detailed characterizations, including NMR, ESI-MS and traveling-wave ion mobility-mass spectrometry (TWIM-MS), all supported the formation of the desired assemblies. AFM and TEM further confirmed the dimensions of assembled nanoprisms. Moreover, the photophysical properties of the ligands and complexes were noticeably different depending upon size and metal ion center.

SARS CoV 3CL is known to be a promising target for development of therapeutic agents against the severe acute respiratory syndrome (SARS). A quinolinone compound was selected via virtual screening, and it was synthetized and tested for enzymatic inhibition . Compound showed potent inhibitory activity (IC=0.44 µmol/L) toward SARS CoV 3CL. Further work on a series of quinolinone derivatives resulted in the discovery of the most potent compound , inhibiting SARS CoV 3CL with an IC of 36.86 nmol/L. The structure-activity relationships were also discussed.

The active site of 3CL proteinase (3CL) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CL of human coronavirus, then it was selected as the reference for molecular docking and database screening. The ligands from two databases were used to search potential lead structures with molecular docking. Several structures from natural products and ACD-SC databases were found to have lower binding free energy with 3CL than that of Ag7088. These structures have similar hydrophobicity to Ag7088. They have complementary electrostatic potential and hydrogen bond acceptor and donor with 3CL, showing that the strategy of anti-SARS drug design based on molecular docking and database screening is feasible.