Synthetic angiotensin II peptide derivatives confer protection against cerebral and severe non-cerebral malaria in murine models

• Published in: Scientific reports Vol. 14; no. 1; p. 4682
• Main Authors: Silva, Adriana F., Torres, Marcelo D. T., Silva, Leandro S., Alves, Flavio L., Miranda, Antonio, Oliveira, Vani X., de la Fuente-Nunez, Cesar, Pinheiro, Ana Acacia S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-02-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/45/611; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensin II - therapeutic use; Animal models; Animals; Antimalarial agents; Antimalarials - pharmacology; Antimalarials - therapeutic use; Antiprotozoal agents; Blood pressure; Brain injury; Cognitive ability; Disease Models, Animal; Humanities and Social Sciences; Humans; Hydrophobicity; Long-term effects; Malaria; Malaria, Cerebral - drug therapy; Malaria, Cerebral - parasitology; Malaria, Cerebral - prevention & control; Mice; Mice, Inbred C57BL; multidisciplinary; Parasitemia; Parasites; Peptides; Peptides - pharmacology; Peptides - therapeutic use; Plasmodium berghei - physiology; Proteolysis; Science; Science (multidisciplinary); Side effects; Synthetic peptides; Vasoconstriction; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-51267-5

Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against
Plasmodium
spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with
Plasmodium berghei
ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.