RT Journal Article SR Electronic T1 Cyclic constrained immunoreactive peptides from crucial P. falciparum proteins: potential implications in malaria diagnostics JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.11.463910 DO 10.1101/2021.10.11.463910 A1 Kapil Vashisht A1 Sukrit Srivastava A1 Vandana A1 Ram Das A1 Supriya Sharma A1 Nitin Bhardwaj A1 Anupkumar R Anvikar A1 Tong-Soo Kim A1 Byoung-Kuk Na A1 Ho-Joon Shin A1 Kailash C Pandey YR 2021 UL http://biorxiv.org/content/early/2021/10/11/2021.10.11.463910.abstract AB Malaria is still a global challenge with significant morbidity and mortality, especially in the African, South-East Asian and Latin American region. Malaria diagnosis is a crucial pillar in the control and elimination efforts, often accomplished by administration of mass-scale Rapid diagnostic tests (RDTs). The inherent limitations of RDTs-failure of detection in low transmission settings, and deletion of one of the target proteins-Histidine rich protein (HRP) are evident from multiple reports; thus necessitating the need to explore novel diagnostic tools/targets. The present study used peptide microarray to screen potential epitopes from 13 antigenic proteins (CSP, EXP1, LSA1, TRAP, AARP, AMA1, GLURP, MSP1, MSP2, MSP3, MSP4, P48/45, HAP2) of P. falciparum. Three cyclic constrained immunoreactive peptides-C6 (EXP1), A8 (MSP2), B7 (GLURP) were identified from 5,458 cyclic constrained peptides (in duplicate) against P. falciparum infected sera. Peptides (C6, A8, B7-cyclic constrained) and (G11, DSQ, NQN-corresponding linear peptides) were fairly immunoreactive towards P. falciparum-infected sera in dot-blot assay. Using indirect ELISA, cyclic constrained peptides (C6 & B7) were found to be specific to P. falciparum infected sera and further, observed to be significantly reactive towards antibodies from field-collected P. falciparum infected sera. Notably, the structural location of the epitopes defines the reactivity, observed by the preferential recognition of cyclic constrained peptides vs linear peptides and corroborated by the homology modeling analysis of selected proteins. In conclusion, the study identified three cyclic constrained immunoreactive peptides (C6, B7 & A8) from P. falciparum secretory/surface proteins and two of them (C6 & B7) were validated for their diagnostic potential with field-collected P. falciparum infected sera samples.Competing Interest StatementThe authors have declared no competing interest.