Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia

Ленева, И. А.; Burtseva, Elena; Yatsyshina, S. B.; Fedyakina, I. Т.; Кириллова, Е. С.; Селькова, Е. П.; Осипова, Е. А.; Maleev, V V

doi:10.1016/j.ijid.2016.01.001

Cited by 39 publications

(56 citation statements)

References 21 publications

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“…These variants possessed a single amino acid substitution in HA2 subunit (K51N, Q42H, Q27N, or K117R), which lead to reduced ability of umifenovir to stabilize the acid‐induced HA conformational changes. The sequence analysis of 108 clinical isolates obtained during 2010 to 2011 influenza season in Russia did not identify substitutions in the HA2 subunit, that can cause umifenovir resistance among influenza A viruses . This finding supports an earlier report on the absence of naturally occurring variants with low susceptibility to umifenovir among human influenza A and B viruses isolated during 2002 to 2005.…”

Section: Introductionsupporting

confidence: 82%

“…Co‐crystal structure of umifenovir with the influenza virus HA glycoprotein indicates that umifenovir binds in a hydrophobic cavity at the interface of the HA protomers in the upper region of the stem . Umifenovir inhibits the replication of a wide range of influenza A, B, and C viruses, including highly pathogenic avian A(H5N1) viruses with 50% effective concentration (EC 50 ) ranging from 7.2 to 23.0 µM . It also maintains antiviral activity against oseltamivir‐ and rimantadine‐resistant influenza viruses.…”

Section: Introductionmentioning

confidence: 99%

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Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study

Leneva

Фалынскова

Махмудова

et al. 2018

Journal of Medical Virology

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Antiviral drugs can play a significant role in the control of influenza. Umifenovir (Arbidol) is licensed and widely used in Russia for the prophylaxis and/or treatment of influenza. We evaluated the susceptibility to umifenovir of reference influenza A and B viruses and influenza A viruses isolated from patients in the ARBITR clinical trial in 2012‐2014 seasons. Using an MDCK cell‐based enzyme‐linked immunosorbent assay (ELISA), we showed that the replication of antigenically dominant human influenza A and B viruses was efficiently inhibited by umifenovir. The wild‐type А/Perth/265/2009 (H1N1)pdm09, A/Fukui/45/2004 (H3N2), and B/Perth/211/2001 viruses and their oseltamivir‐resistant counterparts were susceptible to umifenovir among in vitro laboratory assays. All 18 clinical isolates of influenza A viruses obtained before and during therapy were susceptible to umifenovir with 50% effective concentration (EC 50) ranging from 8.4 ± 1.1 to 17.4 ± 5.4 µM. No molecular markers of umifenovir resistance were identified in influenza viruses isolate d from patients at 3, 5, and 7 days after initiation of therapy. None of the viruses isolated before and during umifenovir therapy displayed reduced susceptibility to neuraminidase (NA) inhibitors. Thus, umifenovir is effective against influenza viruses circulating in 2012‐2014 seasons, and therapy did not lead to the emergence of drug‐resistant variants.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study

Leneva

Фалынскова

Махмудова

et al. 2018

Journal of Medical Virology

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“…Previous in vitro and in vivo studies have shown that Arbidol has broad-spectrum activity against influenza viruses (16)(17)(18)21). Comparison of the Arbidol-binding site in group 2 HAs against the corresponding region in group 1 HA [H1N1 A/Puerto Rico/8/1934 (H1/PR8; PDB ID code 1RU7)] reveals important structural differences between the two groups ( Fig.…”

Section: Discussionmentioning

confidence: 89%

“…Arbidol (umifenovir) is a broad-spectrum antiviral against a number of enveloped and nonenveloped viruses such as influenza, respiratory syncytial (RSV), adenovirus, Coxsackie B5, parainfluenza, Ebola (EBOV), and hepatitis B and C (14)(15)(16)(17)(18)(19)(20). Arbidol demonstrates broad activity against diverse strains and subtypes of influenza A and B viruses and is effective in mice infected with A/California/07/2009 (H1N1), A/Puerto Rico/8/1934 Significance Influenza virus is an important human pathogen.…”

mentioning

confidence: 99%

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Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol

Kadam

Wilson

2016

Proc. Natl. Acad. Sci. U.S.A.

387

359

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The broad-spectrum antiviral drug Arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (HA) fusion machinery. However, the structural basis of the mechanism underlying fusion inhibition by Arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. We determined crystal structures of Arbidol in complex with influenza virus HA from pandemic 1968 H3N2 and recent 2013 H7N9 viruses. Arbidol binds in a hydrophobic cavity in the HA trimer stem at the interface between two protomers. This cavity is distal to the conserved epitope targeted by broadly neutralizing stem antibodies and is ∼16 Å from the fusion peptide. Arbidol primarily makes hydrophobic interactions with the binding site but also induces some conformational rearrangements to form a network of inter-and intraprotomer salt bridges. By functioning as molecular glue, Arbidol stabilizes the prefusion conformation of HA that inhibits the large conformational rearrangements associated with membrane fusion in the low pH of the endosome. This unique binding mode compared with the small-molecule inhibitors of other class I fusion proteins enhances our understanding of how small molecules can function as fusion inhibitors and guides the development of broad-spectrum therapeutics against influenza virus.influenza virus | hemagglutinin | X-ray crystallography | Arbidol | fusion inhibitor

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Heterocyclic compounds as antiviral drugs: Synthesis, structure–activity relationship and traditional applications

Santos

Martins

Bregadiolli

et al. 2021

Journal of Heterocyclic Chem

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A virus outbreak challenges the economic, medical, and public health infrastructure worldwide. More than one virus capable of triggering diseases have been identified per year since 1972, which requires the development of new ways of treatment and prevention, however, such processes are not rapid and easy. With the pandemic scenario experienced since early 2020, several drugs with well-known purposes have gained prominence, due to speculation of their use in the treatment against the new coronavirus. Among the main drugs studied, the vast majority contain a heterocyclic structure. In this review, we presented the traditional and efficient synthesis of 15 drugs that have been studied for the COVID-19 treatment, containing in their structure heterocycles like indole, quinoline, pyrimidone, tetrahydrofuran, pyrrolidine, triazole, pyridazine, pyrazole, pyrrolopyrimidine, azetidine, pyrrolotriazine, pyrazine, tetrahydropyran, benzofuran, spiroketal, and thiazole. Furthermore, we have shown the original applications, as well as their structure-activity relationship and what is their situation as a drug candidate against COVID-19. Thus, the objective was to consolidate the main synthetic and pharmacological aspects involving clinically developed heterocycles that at some point were presented as promising against SARS-CoV-2.

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Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia

Abstract: This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which have continued to circulate in post-pandemic seasons.

Cited by 39 publications

References 21 publications

Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study

Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study

Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol

Heterocyclic compounds as antiviral drugs: Synthesis, structure–activity relationship and traditional applications

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