In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2022-9-16), p. e0274266-
Abstract:
Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales , whose replication depends on the enzymatic activity of the viral L protein. Screening for RVFV inhibitors among compounds with divalent cation-coordinating motifs similar to known viral nuclease inhibitors identified 47 novel RVFV inhibitors with selective indexes from 1.1–103 and 50% effective concentrations of 1.2–56 μM in Vero cells, primarily α-Hydroxytropolones and N-Hydroxypyridinediones. Inhibitor activity and selective index was validated in the human cell line A549. To evaluate specificity, select compounds were tested against a second Bunyavirus, La Crosse Virus (LACV), and the flavivirus Zika (ZIKV). These data indicate that the α-Hydroxytropolone and N-Hydroxypyridinedione chemotypes should be investigated in the future to determine their mechanism(s) of action allowing further development as therapeutics for RVFV and LACV, and these chemotypes should be evaluated for activity against related pathogens, including Hantaan virus, severe fever with thrombocytopenia syndrome virus, Crimean-Congo hemorrhagic fever virus.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0274266
DOI:
10.1371/journal.pone.0274266.g001
DOI:
10.1371/journal.pone.0274266.g002
DOI:
10.1371/journal.pone.0274266.g003
DOI:
10.1371/journal.pone.0274266.g004
DOI:
10.1371/journal.pone.0274266.t001
DOI:
10.1371/journal.pone.0274266.t002
DOI:
10.1371/journal.pone.0274266.t003
DOI:
10.1371/journal.pone.0274266.s001
DOI:
10.1371/journal.pone.0274266.s002
DOI:
10.1371/journal.pone.0274266.s003
DOI:
10.1371/journal.pone.0274266.s004
DOI:
10.1371/journal.pone.0274266.s005
DOI:
10.1371/journal.pone.0274266.s006
DOI:
10.1371/journal.pone.0274266.r001
DOI:
10.1371/journal.pone.0274266.r002
DOI:
10.1371/journal.pone.0274266.r003
DOI:
10.1371/journal.pone.0274266.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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