Leishmaniasis is a chronic disease caused by protozoa of the distinct Leishmania genus transmitted by sandflies of the genus Phlebotomus (old world) and Lutzomyia (new world). Among the molecular factors that contribute to the virulence and pathogenesis of Leishmania are metalloproteases, e.g., glycoprotein 63 (gp63), also known as leishmanolysin or major surface protease (MSP). This protease is a zinc-dependent metalloprotease that is found on the surface of the parasite, abundant in Leishmania promastigote and amastigote. This study describes the prediction of three-dimensional (3D) structures of leishmanolysin (UniProt ID A0A088RJX7) of Leishmania panamensis employing a homology modeling approach. The 3D structure prediction was performed using the SWISS-MODEL web server. The tools PROCHECK, Molprobyty, and Verify3D were used to check the quality of the model, indicating that they are reliable. Best docking configurations were identified applying AutoDock Vina in PyRx 0.8 to obtain a potential antileishmanial activity. Biflavonoids such as lanaroflavone, podocarpusflavone A, amentoflavone, and podocarpusflavone B showed good scores among these molecules. Lanaroflavone appears to be the most suitable compound from binding affinity calculations.
Background The novel SARS-CoV-2, responsible for the COVID-19 pandemic, is the third zoonotic coronavirus since the beginning of the 21 first century, and it has taken more than 6 million human lives because of the lack of immunity causing global economic losses. Consequently, developing a vaccine against the virus represents the fastest way to finish the threat and regain some "normality." Objective Here, we provide information about the main features of the most important vaccine platforms, some of them already approved, to clear common doubts fostered by widespread misinformation and to reassure the public of the safety of the vaccination process and the different alternatives presented. Methods Articles published in open access databases until January 2022 were identified using the search terms "SARS-CoV-2," "COVID-19," "Coronavirus," "COVID-19 Vaccines," "Pandemic," COVID-19, and LMICs or their combinations. Discussion Traditional first-generation vaccine platforms, such as whole virus vaccines (live attenuated and inactivated virus vaccines), as well as second-generation vaccines, like protein-based vaccines (subunit and viral vector vaccines), and third-generation vaccines, such as nanoparticle and genetic vaccines (mRNA vaccines), are described. Conclusions SARS-CoV-2 sequence information obtained in a record time provided the basis for the fast development of a COVID-19 vaccine. The adaptability characteristic of the new generation of vaccines is changing our capability to react to emerging threats to future pandemics. Nevertheless, the slow and unfair distribution of vaccines to low- and middle-income countries and the spread of misinformation are a menace to global health since the unvaccinated will increase the chances for resurgences and the surge of new variants that can escape the current vaccines.
Essential oils (EOs) are widely used as biopesticides and to control bacterial infections. This study describes the ability of six EOs isolated from plants cultivated in Colombia to perform as repellents against Ulomoides dermestoides and as quorum sensing (QS) inhibitors. EOs from Aloysia triphylla, Cymbopogon nardus, Lippia origanoides, Hyptis suaveolens, Swinglea glutinosa and Eucalyptus globulus were repellents classified as Class IV, IV, IV, III, II, and II, respectively, whereas the commercial repellent IR3535 only reached Class II after 2 h exposure. All EOs presented small, but significant inhibitory properties against the QS system in Escherichia coli (pJBA132) at 25 µg/mL after 4 h exposure. These data suggest evaluated EOs from Colombia are sustainable, promising new sources of natural repellents and could be important as anti-quorum sensing molecules.
The genus Malachra L. belongs to the family Malvaceae. It includes herbs or subshrubs of nine accepted species with approximately thirty synonyms, and it has been widely used in community folk medicine to treat health problems including inflammation, nasal obstruction, leishmaniasis, malaria, childbirth, kidney disorders, fever, respiratory tract diseases, among others. From the genus Malachra L., flavonoids, steroids, triterpenes, anthocyanins, leucoanthocyanins, saponins, carbohydrates, phenols, glycosides, and alkaloids have been isolated and identified. Some pharmacological reports have indicated that the genus has antidiarrheal, antiepileptic, antiulcerogenic, antioxidant, anticonvulsant, antiviral, anticancer, antibacterial, anthelmintic, and hepatoprotective properties. However, there have been limited studies of bioactive molecules with pharmacological and biological activities associated with Malachra alceifolia Jacq., Malachra capitata (L.) L., Malachra fasciata Jacq., Malachra radiata (L.) L., Malachra ruderalis Gürke., Malachra rudis Benth., Malachra helodes Mart., Malachra urens Poit. ex Ledeb. & Alderstam., and Malachra officinalis Klotzsch. In this review, we consider the conservation of these species to save the ancestral knowledge of their traditional use in populations, and their pharmacological potential for future studies in search of alternatives for solutions to diseases in humans and animals and tools for the design and search of potential bioactive compounds against infectious and non-infectious agents.
Malachra alceifolia Jacq. (family Malvaceae), known as “malva,” is a medicinal plant used as a traditional therapy in many regions of America, Africa and Asia. Traditionally, this plant is used in the form of extracts, powder and paste by populations for treating fever, stomachache, inflammation, and parasites. However, the ethnopharmacological validation of M. alceifolia has been scarcely researched. This study showed that the chloroform fraction (MA-IC) and subfraction (MA-24F) of the leaves of M. alceifolia exhibited a potential antileishmanial activity against axenic amastigotes of Leishmania mexicana pifanoi (MHOM/VE/60/Ltrod) and had high and moderate cytotoxic effects on the viability and morphology of macrophages RAW 264.7. This study reports, for the first time, possible terpenoid metabolites and derivatives present in M. alceifolia with activity against some biosynthetic pathways in L. mexicana amastigotes. The compounds from the subfractions MA-24F were highly active and were analyzed by gas chromatography-mass spectrometry (GC-MS) and by a molecular docking study in L. mexicana target protein. This study demonstrates the potential modes of interaction and the theoretical affinity energy of the metabolites episwertenol, α-amyrin and methyl commate A, which are present in the active fraction MA-24F, at allosteric sites of the pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase, aldolase, phosphoglucose isomerase, transketolase, arginase and cysteine peptidases A, target proteins in some vital biosynthetic pathways were responsible for the survival of L. mexicana. Some phytoconstituents of M. alceifolia can be used for the search for potential new drugs and molecular targets for treating leishmaniases and infectious diseases. Furthermore, contributions to research and the validation and conservation of traditional knowledge of medicinal plants are needed globally.
Leishmanolisyn (gp63) is a 63 kDa surface metalloprotease belonging to the M8 family (subclan MA (M), metzincines) that is found in both promastigote and amastigote of leishmania ssp. It constitutes one of the virulence factors in the pathogenesis of Leishmania spp., being crucial in its entry into the macrophage and in complement activation. Therefore, gp63 may be a therapeutic alternative for potential new drugs needed to combat this disease. Among the many functional groups of naturally occurring compounds, the biflavonoids amentoflavone (A), lanaraflavone (L), podocarpusflavone A (PA), and podocarpusflovone B (PB) are promising candidate ligands for the treatment of all forms of leishmaniasis. In this study we carried out the validated molecular dynamics simulation with GROMACS, using mean square deviation (RMSD), mean square fluctuation (RMSF), the radius of gyration (Rg), and intermolecular hydrogen bonds (H-bonds) between the gp63 protein of L. major (1LML) in complex with the four biflavonoids. In addition, the free binding energies were estimated using the MM-PBSA method, to determine their stability in the active site of the protein. The computational analysis revealed that the interaction of lanaroflavone (ΔGBing = -156.75 ± 31.91 Kcal/mol for L. major) remained stable in this enzyme, revealing their remarkable potential as a possible antileishmanial agent to combat the Leishmania parasite. On the other hand, amentoflavone, podocarpusflavone A, and B also showed a good affinity for both metalloproteases according to the ΔGbind values obtained.
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