A Mini-review on Potentials Proteins/Peptides Applied for Serodiagnosis of Human Monkeypox Infection and Future Trends.

Monkeypox is a zoonosis that re-emerged in 2022, generating cases in non-endemic countries for the disease and creating a public health issue. The rapid increase in the number of cases kindles a need for quick, inexpensive diagnostic tests for the epidemiological control of the disease. The high cost of molecular tests can make this control more difficult to access in poorer regions, with immunological tests being a more viable option. In this mini-review, a search was conducted in the main databases for peptide and protein options that could be used in the development of serological diagnostic tests. Nine viable registres were found, and seven were selected (two patents and five studies). The main studies used the B21R peptide sequence as it is a high immunogenic epitope. In addition, studies on the improvement of these sequences were also found to avoid cross-reactions against other viruses of the same family, proposing a rational approach using multiepitope recombinant proteins. These approaches demonstrated high sensitivity and specificity values and are seen as viable options for developing new tests. New effective serological testing options, when combined with awareness, disease surveillance, early diagnosis, and rapid communication, form a set of key strategies used by health systems to control the spread of the monkeypox virus.

Rational-Based Discovery of Novel ß-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria.

Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In this context and considering the emergence and spread of drug-resistant P. falciparum isolates, the search for new antimalarial candidates becomes urgent. ß-carbolines alkaloids are good candidates since a wide range of biological activity for these compounds has been reported. Herein, we designed 20 chemical entities and performed an in silico virtual screening against a pool of P. falciparum molecular targets, the Brazilian Malaria Molecular Targets (BRAMMT). Seven structures showed potential to interact with PfFNR, PfPK7, PfGrx1, and PfATP6, being synthesized and evaluated for in vitro antiplasmodial activity. Among them, compounds 3−6 and 10 inhibited the growth of the W2 strain at µM concentrations, with low cytotoxicity against the human cell line. In silico physicochemical and pharmacokinetic properties were found to be favorable for oral administration. The compound 10 provided the best results against CM, with important values of parasite growth inhibition on the 5th day post-infection for both curative (67.9%) and suppressive (82%) assays. Furthermore, this compound was able to elongate mice survival and protect them against the development of the experimental model of CM (>65%). Compound 10 also induced reduction of the NO level, possibly by interaction with iNOS. Therefore, this alkaloid showed promising activity for the treatment of malaria and was able to prevent the development of experimental cerebral malaria (ECM), probably by reducing NO synthesis.