Oseltamivir analogs with potent anti-influenza virus activity

Sumit Kumar; Steven Goicoechea; Sonu Kumar; Catherine M Pearce; Ravi Durvasula; Prakasha Kempaiah; Brijesh Rathi; Poonam

doi:10.1016/j.drudis.2020.06.004

Oseltamivir analogs with potent anti-influenza virus activity

Drug Discov Today. 2020 Aug;25(8):1389-1402. doi: 10.1016/j.drudis.2020.06.004. Epub 2020 Jun 15.

Authors

Sumit Kumar¹, Steven Goicoechea², Sonu Kumar³, Catherine M Pearce⁴, Ravi Durvasula⁵, Prakasha Kempaiah⁵, Brijesh Rathi⁶, Poonam⁷

Affiliations

¹ Department of Chemistry, Miranda House University Enclave, University of Delhi, Delhi, 110007, India.
² Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi, 110007, India; Loyola University Stritch School of Medicine, 2160 South First Avenue, Chicago, IL, USA.
³ Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi, 110007, India.
⁴ Loyola University Stritch School of Medicine, 2160 South First Avenue, Chicago, IL, USA.
⁵ Loyola University Stritch School of Medicine, 2160 South First Avenue, Chicago, IL, USA; Department of Medicine, Loyola University Medical Center, 2160 South First Avenue, Chicago, IL, USA.
⁶ Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi, 110007, India. Electronic address: [email protected].
⁷ Department of Chemistry, Miranda House University Enclave, University of Delhi, Delhi, 110007, India. Electronic address: [email protected].

PMID: 32554062
DOI: 10.1016/j.drudis.2020.06.004

Abstract

Influenza A and B viruses cause seasonal worldwide influenza epidemics each winter, and are a major public health concern and cause of morbidity and mortality. A substantial reduction in influenza-related deaths can be attributed to both vaccination and administration of oseltamivir (OS), which is approved for oral administration and inhibits viral neuraminidase (NA), a transmembrane protein. OS carboxylate (OSC), the active form of OS, is formed by the action of endogenous esterase, which targets NA and is shown to significantly reduce influenza-related deaths. However, the development of resistance in various viral variants, including H3N2 and H5N1, has raised concern about the effectiveness of OS. This comprehensive review covers a range of OS analogs shown to be effective against influenza virus, comparing different types of substituent group that contribute to the activity and bioavailability of these compounds.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antiviral Agents / therapeutic use*
Humans
Life Cycle Stages
Neuraminidase / antagonists & inhibitors
Orthomyxoviridae / growth & development
Orthomyxoviridae Infections / drug therapy*
Oseltamivir / analogs & derivatives*
Oseltamivir / therapeutic use*

Substances

Antiviral Agents
Oseltamivir
Neuraminidase