Remdesivir was shown to inhibit RNA-dependent RNA-polymerases (RdRp) from distinct viral families such as from Filoviridae (Ebola) and Coronaviridae (SARS-CoV, SARS-CoV-2, MERS). In this study, we tested the ability of remdesivir to inhibit RdRps from the Flaviviridae family. Instead of remdesivir, we used the active species that is produced in cells from remdesivir, the appropriate triphosphate, which could be directly tested in vitro using recombinant flaviviral polymerases. Our results show that remdesivir can efficiently inhibit RdRps from viruses causing severe illnesses such as Yellow fever, West Nile fever, Japanese and Tick-borne encephalitis, Zika and Dengue. Taken together, this study demonstrates that remdesivir or its derivatives have the potential to become a broad-spectrum antiviral agent effective against many RNA viruses.

The reactivity of a germylene stabilized by a boraguanidinate ligand with various reagents is reported.

A boraguanidinato-stabilized germylene, [(i-Pr)NB(N-2,6-MeCH)]Ge, reacts with alkynes RC[triple bond, length as m-dash]CR selectively in a 2 : 1 molar ratio to afford 3,4-R,R'-1,2-digermacyclobut-3-enes 1a-e as the products of formal [2 + 2 + 2] cyclization [R/R' = Me/Me (1a), Ph/Ph (1b), Ph/H (1c), t-Bu/H (1d) and Cy/H (1e)]. Ferrocenyl-substituted alkynes react similarly, yielding the corresponding ferrocenylated 3,4-R,R'-1,2-digermacyclobut-3-enes 2a-d [where R/R' = Fc/H (2a), Fc/Me (2b), Fc/Ph (2c), and Fc/Fc (2d); Fc = ferrocenyl]. By contrast, only one of the triple bonds available in conjugated diynes RC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CR is activated with the germylene, while the second one remains intact even in the presence of an excess of the germylene. The exclusive formation of 3,4-R,(C[triple bond, length as m-dash]CR)-1,2-digermacyclobut-3-enes 3a-c [R = Ph (3a), t-Bu(3b), and Fc (3c)] was ascribed to a steric repulsion around the second triple bond. On the other hand, the reaction of the germylene with more flexible dialkyne fc(C[triple bond, length as m-dash]CPh) (fc = ferrocene-1,1'-diyl) proceeded in the expected manner, producing compound 4, where both triple bonds are transformed into 1,2-digermacyclobut-3-ene rings by reaction with four equivalents of the germylene. All compounds were characterized by multinuclear NMR spectroscopy, Raman and IR spectroscopy, and in the case of 1a-c, 2a, 2c, 3a, 3b and 4, also by single-crystal X-ray diffraction analysis. The ferrocenyl substituted compounds were studied by cyclic voltammetry (CV). Finally, the plausible reaction pathway was studied for a model reaction of [(i-Pr)NB(N-2,6-MeCH)]Ge with MeC[triple bond, length as m-dash]CMe using DFT computations.

The titled germylene was shown to be able to activate various chemical bonds (C–N, C–F or CO) depending on the substrate used.