An Isomer of Galidesivir That Potently Inhibits Influenza Viruses and Members of the Bunyavirales Order
Year: 2023
Type: article
Abstract: We report for the first time the antiviral activities of two iminovirs (antiviral imino- C -nucleosides) 1 and 2, structurally related to galidesivir (Immucillin A, BCX4430). An iminovir containing the 4-aminopyrrolo[2,1- f ][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 Bunyavirales order. We also report the first syntheses of ProTide prodrugs of iminovir monophosphates, which unexpectedly displayed poorer viral inhibition than their parent nucleosides in vitro . An efficient synthesis of the 4-aminopyrrolo[2,1- f ][1,2,4-triazine]-containing iminovir 2 was developed to enable preliminary in vivo studies, wherein it displayed significant toxicity in BALB/c mice and limited protection against influenza. Further modification of this anti-influenza iminovir will therefore be required to improve its therapeutic value.
Source: ACS Medicinal Chemistry Letters
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Utah State University, University of Otago, Foundation for Research, Science and Technology, University of Auckland, Victoria University of Wellington, Victoria University, Ministry of Business, Innovation and Employment, Maurice Wilkins Centre for Molecular Biodiscovery, National Institutes of Health, Ferrier Research Institute, Victoria University of Wellington, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W4361270142