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

IF 2.5 4区 医学 Q2 PARASITOLOGY Memorias do Instituto Oswaldo Cruz Pub Date : 2023-07-10 eCollection Date: 2023-01-01 DOI:10.1590/0074-02760230056
Desiree Dos Santos Nunes, Luiza M Higa, Régis Linhares Oliveira, Lendel Correia da Costa, Larissa Maciel Bomfim, Cássia Cristina Alves Gonçalves, Diana Mariani, Dennis E Hruby, Carolina Moreira Voloch, Terezinha Marta Pereira Pinto Castiñeiras, Amilcar Tanuri, Clarissa R Damaso
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Abstract

Background: 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.

Objectives: Here we investigated the tecovirimat susceptibility of 18 clinical isolates of monkeypox virus (MPXV) obtained from different regions of Brazil.

Methods: 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.

Findings: 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.

Main conclusions: 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.

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十八种临床分离的人猴痘病毒对替考韦瑞的体外敏感性。
背景:2022 年,一场始于欧洲国家的麻风腮疫情通过人际传播蔓延至全球。病例大多较轻,但也有严重临床表现的报告。在这些病例中,特考韦瑞是治疗病情加重患者的首选药物:目的:我们在此研究了从巴西不同地区获得的18株猴痘病毒(MPXV)临床分离株对替考韦利马特的敏感性:方法:在感染了每种 MPXV 分离物的单层细胞中加入不同浓度的特考韦瑞马。72 小时后,对细胞进行固定和染色,以观察斑块、计数和测量。对每种 MPXV 分离物的 F13L 基因直向同源物进行聚合酶链反应(PCR)扩增、测序,并分析预测的蛋白质序列:18个MPXV分离株产生了不同大小的斑块。尽管所有分离株都对药物高度敏感,但有两种分离株显示出不同的反应曲线和 IC50 值。然而,特考韦利马特的靶蛋白 F13(VP37)在所有 MPXV 分离物中都是 100%保守的,因此不能解释敏感性的差异:我们的研究结果支持对不同的 MPXV 分离物进行特考韦瑞敏感性筛查,这是一种重要的工具,可以更好地利用低收入国家有限的特考韦瑞剂量来治疗麻腮风患者。
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
91
审稿时长
3-8 weeks
期刊介绍: Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.
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