Different Inhibitory Potencies of Oseltamivir Carboxylate, Zanamivir, and Several Tannins on Bacterial and Viral Neuraminidases as Assessed in a Cell-Free Fluorescence-Based Enzyme Inhibition Assay

Abstract

Neuraminidase is a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA)-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1) and bacterial Vibrio cholerae neuraminidase (VCNA). Compared to the positive controls, all tested polyphenols displayed a weak inhibition of the viral enzyme but similar or even higher potency on the bacterial neuraminidase. Structure–activity relationship analyses revealed the presence of galloyl groups and the hydroxylation pattern of the flavan skeleton to be crucial for inhibitory activity. The combination of zanamivir and EPs® 7630 (root extract of Pelargonium sidoides) showed synergistic inhibitory effects on the bacterial neuraminidase. Co-crystal structures of VCNA with oseltamivir carboxylate and zanamivir provided insight into bacterial versus viral enzyme-inhibitor interactions. The current data clearly indicate that inhibitor potency strongly depends on the biological origin of the enzyme and that results are not readily transferable. The therapeutic relevance of our findings is briefly discussed.

Beyond the Biological Effect of a Chemically Characterized Poplar Propolis: Antibacterial and Antiviral Activity and Comparison with Flurbiprofen in Cytokines Release by LPS-Stimulated Human Mononuclear Cells

“…PP showed an interesting low value of IC 50 , 35.29 µg/mL, similar to other effective herbal extracts such as Salix spp. or Nelia meyeri Schwantes, recently tested by Quosdorf et al [16]. IC 50 value of PP is also consistent with a concentration higher than the non-cytotoxic one.…”

Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters

“…In 2017, Quosdorf et al [48] analyzed the relationship between structure and anti-activity for flavan-3-ols including EGCG ( 1 ) by 2′-(4-methylumbelliferyl)-α- d - N -acetylneuraminic acid (MUNANA)-based activity assay. Compared to oseltamivir carboxylate and zanamivir, anti-NA activities were weak with all flavan-3-ols.…”

“…Regarding these biological properties, EGCG ( 1 ) has been reported to possess a broad spectrum of antiviral activities against DNA viruses such as herpes simplex virus (HSV; Herpesviridae ) [5,6,7,8,9,10,11], adenovirus ( Adenoviridae ) [10,12], human papilloma virus (HPV; Papovaviridae ) [13], and hepatitis B virus (HBV; Hepadnaviridae ) [14], and against (+)-RNA viruses such as hepatitis C virus (HCV; Flaviviridae ) [10,15,16,17,18,19], Zika virus (ZIKV; Flaviviridae ) [20,21,22,23], dengue virus (DENV; Flaviviridae ) [23,24], West Nile viruses (WNV; Flaviviridae ) [23], Chikungunya virus (CHIKV; Togaviridae ) [25], and Porcine Reproductive and Respiratory virus (PRRS; Atteriviridae ) [26], and (−)-RNA viruses such as human immunodeficiency virus (HIV; Retroviridae ) [27,28,29,30,31,32,33,34,35,36], Ebola virus (EBOV; Filoviridae ) [37] and influenza virus ( Orthomyxoviridae ) [2,10,38,39,40,41,42,43,44,45,46,47,48]. …”

Semi‐Synthetic Sialic Acid Probes for Challenging the Substrate Promiscuity of Enzymes in the Sialoconjugation Pathway

“…The pentadienyl analog 13 and saturated 14 show a branched structure motif, which is similar in size and polarity to that present in the well-known antiviral drug Oseltamivir (17) used for influenza treatment. [20] Corresponding derivatives or even conjugates of 13/14 themselves promise to have sialidase inhibitory activity as suggested by their significant structural similarity.…”

“…Sialidase inhibitors such as Oseltamivir, Zanamivir or natural products (e. g., siastatin B) were shown to be successful antiviral drugs and/or potential antibacterial agents. [20] However, the substrate and inhibitor specificity profiles of sialidases was less well studied, despite their use as important analytical tools, and hence depends on the synthetic availability of Sia analogs and their glycoconjugates.…”