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Background Although the COVID-19 pandemic has diminished in intensity, the virus continues to circulate globally. The SARS-CoV-2 main protease (Mpro) is a key enzyme in the life cycle of the virus, making it important for the development of treatments against future variants of the virus. In this work, Peruvian natural compounds were evaluated against different mutations of the SARS-CoV-2 Mpro. Methods In silico techniques such as virtual screening, all-atom molecular dynamics simulations, and energy estimation analysis were applied. Results Of the tested compounds by virtual screening, rutin was identified as the best binding agent against the different proposed Mpro mutations. In addition, computational simulations and energy estimation analysis demonstrated the high structural and energetic stability between the Mpro-rutin systems. Conclusions Overall, our study identified rutin as the most promising compound with a strong affinity for various Mpro mutations, potentially playing a key role in the development of new treatments for emerging viral variants.

Background The coronavirus disease (COVID-19) pandemic continues to be a public health problem worldwide. Several therapeutic targets of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, whereas the main protease (Mpro) is necessary for virus replication. Since SARS- CoV-2 Mpro mutation rates are inherently high, searching for new inhibitors remains challenging. Herein, this work aimed to evaluate 84 natural compounds from Peruvian sources against different mutations on the Mpro target. Methods We applied virtual screening, all-atom molecular dynamics simulations, and binding free energy estimation by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA). Results The virtual screening results helped us identify rutin as the top compound against different Mpro mutations. Likewise, the computational simulations demonstrated the high structural stability of the Mpro-rutin system. Conclusions his research evaluated the antiviral capacity of Peruvian sources against SARS-CoV-2 Mpro and its mutations, which could be important in preventing and treating SARS-CoV-2 infection.

Abstract Since the number of drugs based on natural products (NPs) represents a large source of novel pharmacological entities, NPs have acquired significance in drug discovery. Peru is considered a megadiverse country with many endemic species of plants, terrestrial, and marine animals, and microorganisms. NPs databases have a major impact on drug discovery development. For this reason, several countries such as Mexico, Brazil, India, and China have initiatives to assemble and maintain NPs databases that are representative of their diversity and ethnopharmacological usage. We describe the assembly, curation, and chemoinformatic evaluation of the content and coverage in chemical space, as well as the physicochemical attributes and chemical diversity of the initial version of the Peruvian Natural Products Database (PeruNPDB), which contains 280 natural products. Access to PeruNPDB is available for free ( https://perunpdb.com.pe/ ). The PeruNPDB’s collection is intended to be used in a variety of tasks, such as virtual screening campaigns against various disease targets or biological endpoints. This emphasizes the significance of biodiversity protection both directly and indirectly on human health.

Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future.