Monika Aparecida Coronado

: Recent omics studies (cytogenomics, genomics, and transcriptomics) have provided extensive information on Chagas disease (CD) vectors. Here, we conduct a review of proteomic and metabolomic studies on these insect vectors. We address proteomic studies in triatomines, focusing on the identification and characterization of proteins in their saliva, midgut, and salivary glands, emphasizing their role in blood feeding by providing vasodilatory and anticoagulant substances, along with anti-inflammatory and antiplatelet activities. In addition, the review investigates protein diversity in different triatomine species, highlighting the importance of proteomic analysis in understanding adaptation to hematophagy, genetic evolution, and vector defense mechanisms. Metabolomic studies on CD vectors have revealed crucial information about their biology because metabolites correlate with the presence of Trypanosoma cruzi (T. cruzi), suggesting roles in the parasite–vector interaction. Additionally, some studies have predicted T. cruzi infection and observed altered metabolomes after feeding on infected blood, providing information about vector exposure to the parasite.

Climate change has enhanced the spread of arboviruses such as Chikungunya virus (CHIKV). CHIKV is a re-emerging virus from the family Togaviridae that has spread globally, causing numerous outbreaks. The lack of antiviral therapy against CHIKV makes it a significant threat to public health. Cleavage of the viral polyprotein depends on the catalytic activity of nsP2, which is essential for viral replication. Due to this critical role, the nsP2 protease is a promising target for antiviral drug development. Animal venom-derived peptides have shown great potential against a variety of diseases, including infections, cancer, and neurodegenerative disorders. In this study, we evaluated the inhibitory effects and properties of pantinin-1, a peptide derived from the scorpion Pandinus imperator with broad antimicrobial activity, against CHIKV nsP2 protease. Pantinin-1 effectively inhibited CHIKV nsP2 protease, with a half-maximal inhibitory concentration (IC ₅₀ ) of 6.4 ± 2.04 µM and complete inhibition at 175 µM. Further analysis revealed that pantinin-1 acts as a competitive inhibitor with low micromolar affinity and showed no toxicity up to 20 µM in cell culture. Lastly, using molecular docking with subsequent molecular dynamics, the protein–peptide interaction was analyzed, and the key residues involved in the interaction with the protease were predicted. These findings highlight the potential inhibitory effect of pantinin-1 as a lead candidate targeting nsP2 protease.

Chikungunya virus (CHIKV) is an emerging arbovirus whose replication relies on the multifunctional nonstructural protein 2 (nsP2), particularly its viral protease (nsP2 ^pro ), which is essential for polyprotein processing. In this study, we investigated how interactions with nucleic acids influence nsP2 ^pro activity. Using high-throughput sequencing–fluorescent ligand interaction profiling, we identified specific single-stranded DNA aptamers that enhanced nsP2 ^pro activity. Additionally, both random single-stranded DNA and single-stranded RNA were found to stimulate protease activity, whereas double-stranded DNA showed no such effect. Circular dichroism spectroscopy and secondary structure predictions confirmed that the identified aptamers adopt stable folded conformations. Similarly, structured RNA sequences were also capable of promoting protease activity. The observed stimulatory effect depended on the nucleic acid strand type, length, and buffer conditions, suggesting the involvement of electrostatic interactions. Molecular docking analyses further let us assume that these nucleic acids interact specifically with the nsP2 ^pro methyltransferase domain. Our findings provide novel insights into the regulation of nsP2 ^pro , enhancing our understanding of CHIKV replication mechanisms, and may guide future antiviral development strategies.

Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its pathology. One key feature of AD is the presence of amyloid-β (Aβ) peptides, which form amyloid plaques, and therefore, it is a primary target for treatment studies. Naturally occurring peptides have garnered attention for their potential pharmacological benefits, particularly in the central nervous system. In this study, nine peptide derivatives of Crotamine, a polypeptide from Crotalus durissus terrificus Rattlesnake venom, as well as one d-enantiomer, were evaluated for their ability to modulate Aβ₄₂ aggregation through various assays such as ThT, QIAD, SPR, and sFIDA. All tested peptides were able to decrease Aβ₄₂ aggregation and eliminate Aβ₄₂ aggregates. Additionally, all of the peptides showed an affinity for Aβ₄₂. This study is the first to describe the potential of crotamine derivative peptides against Aβ₄₂ aggregation and to identify a promising d-peptide that could be used as an effective pharmacological tool against AD in the future.

The arbovirus Chikungunya (CHIKV) is transmitted by Aedes mosquitoes in urban environments, and in humans, it triggers debilitating symptoms involving long-term complications, including arthritis and Guillain-Barré syndrome. The development of antiviral therapies is relevant, as no efficacious vaccine or drug has yet been approved for clinical application. As a detailed map of molecules underlying the viral infection can be obtained from the metabolome, we validated the metabolic signatures of Vero E6 cells prior to infection (CC), following CHIKV infection (CV) and also upon the inclusion of the nsP2 protease inhibitor wedelolactone (CWV), a coumestan which inhibits viral replication processes. The metabolome groups evidenced significant changes in the levels of lactate, myo-inositol, phosphocholine, glucose, betaine and a few specific amino acids. This study forms a preliminary basis for identifying metabolites through HR-MAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Ressonance Spectroscopy) and proposing the affected metabolic pathways of cells following viral infection and upon incorporation of putative antiviral molecules.

The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes. The present study describes the possible induction of tau aggregation by the SARS-CoV-2 3CL protease (3CL^pro) possibly relevant in neuropathology. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.

The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes. The present study describes the possible induction of protein aggregation by the SARS-CoV-2 3CL protease (3CL ^pro ) possibly relevant in neuropathology, such as aggregation of tau, alpha-synuclein and TPD-43. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC₅₀ values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection.