[Assessment of the antiviral activity of 2HCl*H-His-Rim compound compared to the anti-influenza drug Arbidol for influenza caused by A/duck/Novosibirsk/56/05 (H5N1) (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae).]
Adamantane
/ analogs & derivatives
Animals
Antiviral Agents
/ pharmacology
Chlorocebus aethiops
Drug Resistance, Viral
/ drug effects
Ducks
Humans
Indoles
/ pharmacology
Influenza A Virus, H5N1 Subtype
Influenza in Birds
/ drug therapy
Influenza, Human
/ drug therapy
Microbial Sensitivity Tests
Vero Cells
Viral Load
/ drug effects
Virus Replication
/ drug effects
Influenza A virus
adamantan
antiviral activity
arbidol
drug resistance
Journal
Voprosy virusologii
ISSN: 2411-2097
Titre abrégé: Vopr Virusol
Pays: Russia (Federation)
ID NLM: 0417337
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
12
2019
accepted:
24
12
2019
entrez:
14
3
2020
pubmed:
1
1
2019
medline:
13
4
2021
Statut:
ppublish
Résumé
The emergence of influenza virus strains with drug resistance to antiviral drugs requires finding new compounds, potential direct-acting inhibitors. Аdamantane compounds drugs used since the 1960s have lost their activity the resulting due to resistance. Only neuraminidase inhibitors such as zanamivir and oseltamivir have been approved by WHO for influenza treatment. The Russian pharmaceutical drug Arbidol (Umifenovirum) is actively used in Russia. This drug is used to treat influenza in Russia, China and most post-Soviet republics. This work presents a new derivative of aminoadamantane - dichlorohydrate L-histidyl-1-adamantayl ethylamine (2HCl*H-His-Rim), which showed a high level of inhibition of strains of influenza virus A in vitro. Comparison of antiviral properties of the new synthetic low-molecular inhibitor of influenza A virus replication and Arbidol drug pharmacy. The compound 2HCl*H-His-Rim was obtained by classical peptide synthesis methods. It was identified by methods of mass spectrometry, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Its antiviral properties have been studied in vitro for monolayer of cells Vero-E6 infected with a high-virulent strain of A/duck/Novosibirsk/56/06 (H5N1) influenza virus at various injection schemes of the investigated compounds. The antiviral activity of the 2HCl*H-His-Rim compound against the highly pathogenic strain of the influenza A/H5N1 virus was slightly higher than for the known pharmacy drug arbidol. The difference in antiviral activity of these two compounds is explained by different mechanisms of action on the viral particle. The 2HCl*H-His-Rim compound can be recommended as a candidate for preclinical and clinical trials in order to obtain an etiotropic antiviral drug based on it, due to its high efficacy and economic and synthetic availability. The synthetic compound 2HCl*H-His-Rim acts on influenza A virus variants resistant to Rimantadine and Amantadine.
Identifiants
pubmed: 32168440
doi: 10.36233/0507-4088-2019-64-6-268-273
doi:
Substances chimiques
Antiviral Agents
0
Indoles
0
umifenovir
93M09WW4RU
Adamantane
PJY633525U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
rus
Sous-ensembles de citation
IM
Pagination
268-273Déclaration de conflit d'intérêts
The authors declare no conflict of interest.