Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2025
Characterization of genes involved in hemoglobin degradation in Plasmodium vivax isolates from Chennai, India, and species of non-human primate malaria.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shalini Sneh, Mishra Neelima, Verma Sonia, Kale Sonal, Mallick Prashant K, Prajapati Surendra K, Kumar Anil, Srivastava Nalini, Joshi Hema, Eapen Alex, Singh Om P
Аннотация
BACKGROUND: Plasmodium vivax poses a persistent obstacle to global malaria elimination efforts. While no detectable chloroquine (CQ) resistance has been found in patient samples from India, this observation awaits confirmation. The mechanism of action of CQ continues to be debated. Hemoglobin degradation within the parasite's food vacuole (FV) is integral to its survival and serves as a promising target for antimalarial drug development.
METHODS: This study investigates the molecular and structural characteristics of three key FV enzymes-plasmepsin IV (PM_IV), heme detoxification protein (HDP), and falcilysin (FLN)-in P. vivax isolates from India. Genomic DNA from 30 clinical isolates and three chloroquine (CQ)-resistant reference strains was analyzed to identify mutations and assess structural implications through homology modelling.
RESULTS: Several nonsynonymous mutations were detected, including c.493G>A (Val165Ile) in PM_IV, c.1537A>G (Asn513Asp), and c.2027G>A (Gly676Asp) in FLN, and a novel in-frame duplication c.28_33dup (ATCGCC) in HDP. Structural modelling revealed that these mutations did not affect the active binding sites of the enzymes.
CONCLUSIONS: The genes were highly conserved across isolates, underscoring their important (essential) roles in parasite survival and their potential as drug targets. These are the first findings from the Indian subcontinent that provide critical insights into the mechanisms of chloroquine (CQ) action and resistance, paving the way for novel therapeutic strategies against Plasmodium vivax malaria.
METHODS: This study investigates the molecular and structural characteristics of three key FV enzymes-plasmepsin IV (PM_IV), heme detoxification protein (HDP), and falcilysin (FLN)-in P. vivax isolates from India. Genomic DNA from 30 clinical isolates and three chloroquine (CQ)-resistant reference strains was analyzed to identify mutations and assess structural implications through homology modelling.
RESULTS: Several nonsynonymous mutations were detected, including c.493G>A (Val165Ile) in PM_IV, c.1537A>G (Asn513Asp), and c.2027G>A (Gly676Asp) in FLN, and a novel in-frame duplication c.28_33dup (ATCGCC) in HDP. Structural modelling revealed that these mutations did not affect the active binding sites of the enzymes.
CONCLUSIONS: The genes were highly conserved across isolates, underscoring their important (essential) roles in parasite survival and their potential as drug targets. These are the first findings from the Indian subcontinent that provide critical insights into the mechanisms of chloroquine (CQ) action and resistance, paving the way for novel therapeutic strategies against Plasmodium vivax malaria.