In vitro susceptibility of eighteen clinical isolates of human monkeypox virus to tecovirimat

In 2022, an outbreak of mpox that started in European countries spread worldwide through human-to-human transmission. Cases have been mostly mild, but severe clinical presentations have been reported. In these cases, tecovirimat has been the drug of choice to treat patients with aggravated disease....

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Published in:Memórias do Instituto Oswaldo Cruz 2023-01, Vol.118, p.e230056-e230056
Main Authors: Nunes, Desiree Dos Santos, Higa, Luiza M, Oliveira, Régis Linhares, da Costa, Lendel Correia, Bomfim, Larissa Maciel, Gonçalves, Cássia Cristina Alves, Mariani, Diana, Hruby, Dennis E, Voloch, Carolina Moreira, Castiñeiras, Terezinha Marta Pereira Pinto, Tanuri, Amilcar, Damaso, Clarissa R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Benzamides
Humans
Monkeypox virus - genetics
Mpox (monkeypox)
PARASITOLOGY
TROPICAL MEDICINE
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Summary:In 2022, an outbreak of mpox that started in European countries spread worldwide through human-to-human transmission. Cases have been mostly mild, but severe clinical presentations have been reported. In these cases, tecovirimat has been the drug of choice to treat patients with aggravated disease. Here we investigated the tecovirimat susceptibility of 18 clinical isolates of monkeypox virus (MPXV) obtained from different regions of Brazil. Different concentrations of tecovirimat were added to cell monolayers infected with each MPXV isolate. After 72 hours, cells were fixed and stained for plaque visualization, counting, and measurement. The ortholog of F13L gene from each MPXV isolate was polymerase chain reaction (PCR)-amplified, sequenced, and the predicted protein sequences were analyzed. The eighteen MPXV isolates generated plaques of different sizes. Although all isolates were highly sensitive to the drug, two showed different response curves and IC50 values. However, the target protein of tecovirimat, F13 (VP37), was 100% conserved in all MPXV isolates and therefore does not explain the difference in sensitivity. Our results support screening different MPXV isolates for tecovirimat susceptibility as an important tool to better use of the restricted number of tecovirimat doses available in low-income countries to treat patients with mpox.
ISSN:0074-0276
1678-8060
1678-8060
DOI:10.1590/0074-02760230056