Molecular surveillance of Kelch-13 gene in Plasmodium falciparum field isolates from Mayurbhanj District, Odisha, India, and in silico artemisinin-Kelch-13 protein interaction study.
Parasitol Res
; 122(3): 717-727, 2023 Mar.
Article
em En
| MEDLINE
| ID: mdl-36729138
ABSTRACT
The global malaria control and elimination program faces major threats due to the emergence and transmission of the anti-malarial drug-resistant strain of Plasmodium falciparum. Monitoring of artemisinin (ART) resistance marker Kelch-13 in the malaria-endemic region is essential in mitigating the disease's morbidity and mortality. The current study aimed to generate baseline information for further surveillance in the future. The current research was designed and conducted from July 2019 to June 2021 to monitor Pfkelch13 mutation at the molecular level in the eastern region of India. We also conducted an in silico study to understand the drug-protein interactions between ART and the protein crystal of PfKelch13 (KELCH) with PDB id4ZGC. The kelch-13 gene was amplified by nested polymerase chain reaction (PCR) and sequenced through the Sanger sequencing method. Reference 3D7 clone (PF3D7_1343700) was used to align and probe all the sequences. The sequence analysis showed the absence of validated or associated mutation in the Kelch-13 propeller domain. The absence of natural selection in drug resistance was confirmed by the Tajima test. Further, in silico interaction studies between the drug ART and the Kelch propeller domain of P. falciparum were evaluated by structure predictions, molecular docking, molecular dynamics (MD) simulations, and estimations of binding free energies for the KELCH-ART complex. The results were compared with the apoprotein (KELCH-APO). The study confirmed the favorable binding of ART with the Kelch-13 propeller domain.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Malária Falciparum
/
Artemisininas
/
Antimaláricos
Tipo de estudo:
Screening_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Parasitol Res
Assunto da revista:
PARASITOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Índia