Antivirals Targeting the Neuraminidase.

@article{Gubareva2020AntiviralsTT,
  title={Antivirals Targeting the Neuraminidase.},
  author={Larisa V Gubareva and Teena Mohan},
  journal={Cold Spring Harbor perspectives in medicine},
  year={2020}
}
  • L. GubarevaT. Mohan
  • Published 9 March 2020
  • Biology, Chemistry
  • Cold Spring Harbor perspectives in medicine
The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired… 

Figures from this paper

Sialidase Inhibitors with Different Mechanisms

This Perspective describes sialidase inhibitors with different mechanisms and their activities and future potential, which include transition-state analogue inhibitors, mechanism-based inhibitors, suicide substrate inhibitors, product analogue inhibitor, and natural product inhibitors.

A Novel Synthetic Dual Agonistic Liposomal TLR4/7 Adjuvant Promotes Broad Immune Responses in an Influenza Vaccine With Minimal Reactogenicity

A novel combination liposomal adjuvant contributes to a more broadly protective vaccine while demonstrating an attractive safety profile.

Broad-Spectrum Activity of Small Molecules Acting against Influenza a Virus: Biological and Computational Studies

A new drug-like compounds with antiviral activity toward two A/H1N1 Influenza virus strains, which were demonstrated to interfere with the processes mediated by hemagglutinin (HA), are identified and their ability to act against the A/ H3N2 viral strain has been evaluated in hemag glutination inhibition (HI) assays.

In Vitro and In Vivo Antiviral Studies of New Heteroannulated 1,2,3-Triazole Glycosides Targeting the Neuraminidase of Influenza A Viruses

In vitro and in vivo the antiviral activity of new 1,2,3-triazole glycosides incorporating benzimidazole, benzooxazoles, or benzotriazole cores synthesized by using a click approach was tested and showed that varying the glycosyl moiety in the synthesized glycoside enhanced antiviralActivity.

Facial Synthesis and Bioevaluation of Well-Defined OEGylated Betulinic Acid-Cyclodextrin Conjugates for Inhibition of Influenza Infection

The structure-activity relationships of multivalent BA-cyclodextrin conjugates were discussed, highlighting thatMultivalent BA derivatives may be potential antiviral agents against influenza infection.

Intermolecular Mechanism and Dynamic Investigation of Avian Influenza H7N9 Virus’ Susceptibility to E119V-Substituted Peramivir–Neuraminidase Complex

This study investigates the mechanism and dynamism on the susceptibility of the E119V mutation on the peramivir–neuraminidase complex relative to the wildtype complex at the intermolecular level and unveils the residues responsible for the complex conformations.

Evolution of Influenza Viruses—Drug Resistance, Treatment Options, and Prospects

The aim of the review was to describe the consequences of the variability of influenza viruses, mutations, and recombination, which allow viruses to overcome species barriers, causing epidemics and pandemics.

Baloxavir Treatment Delays Influenza B Virus Transmission in Ferrets and Results in Limited Generation of Drug-Resistant Variants

The findings confirm the antiviral potency of baloxavir against IBVs, while supporting optimization of the dosing regimen to maximize clinical benefit.

References

SHOWING 1-10 OF 214 REFERENCES

Mechanism-Based Covalent Neuraminidase Inhibitors with Broad-Spectrum Influenza Antiviral Activity

A new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme are reported, with efficacies comparable to that of the neuraminIDase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro.

Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

These anti-influenza drugs have been used as templates for the development of new neuraminidase inhibitors through structure-activity relationship studies and the synthetic routes to these commercial drugs are reviewed.

Universal anti-neuraminidase antibody inhibiting all influenza A subtypes.

A novel approach to antiviral therapy for influenza.

  • P. Colman
  • Biology, Chemistry
    The Journal of antimicrobial chemotherapy
  • 1999
Zanamivir (4-guanidino-Neu5Ac2en) is one of the most potent of the sialic acid analogues described to date and is expected to minimize the viability of drug-resistant virus that might arise through mutations in the enzyme active site.

Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses

Tests indicate that CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants, and the binding stability of R-125489 to various subtypes of influenza virus was assessed and compared with that of other NA inhibitors.

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

It is confirmed that NA-specific antibodies can protect against A(H7N9) infection and suggests that in vitro properties can be used to rank antibodies with therapeutic potential.

Influenza neuraminidase operates via a nucleophilic mechanism and can be targeted by covalent inhibitors.

It is shown that 2α,3ax-difluoro-N-acetylneuraminic acid forms a covalent bond with influenza neuraminidase Tyr406 and the compound was found to possess potent anti-influenza activity against both influenza A and B viruses.

Three new powerful oseltamivir derivatives for inhibiting the neuraminidase of influenza virus.

Identification of neuraminidase inhibitors against dual H274Y/I222R mutant strains

Three new inhibitors situated at the sialic-binding site with inhibitory effects for normal neuraminidase, but lowered effects for mutant strains are identified, suggesting that the new inhibitors can be used as a starting point to combat drug-resistant strains.
...