An Isomer of Galidesivir That Potently Inhibits Influenza Viruses and Members of the Order

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Apr 20

PMID 37077387

Authors

Kevin J Sparrow

Rinu Shrestha

James M Wood

Keith Clinch

Brett L Hurst

Hong Wang

Brian B Gowen

Justin G Julander

E Bart Tarbet

Alice M McSweeney

Vernon K Ward

Gary B Evans

Lawrence D Harris

Affiliations

Soon will be listed here.

Abstract

We report for the first time the antiviral activities of two (antiviral imino--nucleosides) and , structurally related to galidesivir (Immucillin A, BCX4430). An containing the 4-aminopyrrolo[2,1-][1,2,4-triazine] nucleobase found in remdesivir exhibited submicromolar inhibition of multiple strains of influenza A and B viruses, as well as members of the order. We also report the first syntheses of ProTide prodrugs of monophosphates, which unexpectedly displayed poorer viral inhibition than their parent nucleosides . An efficient synthesis of the 4-aminopyrrolo[2,1-][1,2,4-triazine]-containing was developed to enable preliminary studies, wherein it displayed significant toxicity in BALB/c mice and limited protection against influenza. Further modification of this anti-influenza will therefore be required to improve its therapeutic value.

Citing Articles

Galidesivir Triphosphate Promotes Stalling of Dengue-2 Virus Polymerase Immediately Prior to Incorporation.

Deshpande S, Huo W, Shrestha R, Sparrow K, Wood J, Evans G ACS Infect Dis. 2023; 9(8):1658-1673.

PMID: 37488090 PMC: 10739630. DOI: 10.1021/acsinfecdis.3c00311.

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