Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil’s semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARS-CoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.

Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0^®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.

As leishmanioses são um grupo de doenças negligenciadas causadas por protozoários intracelulares do gênero Leishmania. Suas principais formas clínicas são a tegumentar (LT) e a visceral (LV). Atualmente a terapêutica contra a leishmaniose baseia-se na utilização de cinco fármacos: os antimoniais pentavalentes, a anfotericina B e a sua formulação lipossômica, a miltefosina, a paromomicina e a pentamidina. Estes compostos apresentam limitações que dificultam a adesão do paciente ao tratamento como: a elevada toxicidade e a necessidade de administração prolongada por via parenteral, além da possível seleção de cepas resistentes. Assim, utilizando a revisão narrativa de literatura, buscou-se elucidar um panorama do tratamento atual da leishmaniose, seus mecanismos de ação elucidados, sua toxicidade atribuída, seus efeitos adversos e vias de administração. Para tanto, os dados mais atualizados disponíveis na literatura foram trazidos para facilitar o acesso às informações sobre as opções terapêuticas, além das novas alternativas terapêuticas e perspectivas de vacinas contra esta doença negligenciada.