The novel coronavirus SARS-CoV-2 has been affecting the world, causing severe pneumonia and acute respiratory syndrome, leading people to death. Therefore, the search for anti-SARS-CoV-2 compounds is pivotal for public health. Natural products may present sources of bioactive compounds; among them, flavonoids are known in literature for their antiviral activity. Siparuna species are used in Brazilian folk medicine for the treatment of colds and flu. This work describes the isolation of 3,3′,4′-tri-O-methyl-quercetin, 3,7,3′,4′-tetra-O-methyl-quercetin (retusin), and 3,7-di-O-methyl-kaempferol (kumatakenin) from the dichloromethane extract of leaves of Siparuna cristata (Poepp. & Endl.) A.DC., Siparunaceae, using high-speed countercurrent chromatography in addition to the investigation of their inhibitory effect against SARS-CoV-2 viral replication. Retusin and kumatakenin inhibited SARS-CoV-2 replication in Vero E6 and Calu-3 cells, with a selective index greater than lopinavir/ritonavir and chloroquine, used as control. Flavonoids and their derivatives may stand for target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.

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The SARS-CoV-2 virus infection led to millions of deaths during the COVID-19 pandemic. Hundreds of workers from several other Brazilian cities, as well as from other countries, arrive daily in Macaé to work in the oil supply chain, making this city a putative hotspot for the introduction of new viral lineages. In this study, we performed a genomic survey of SARS-CoV-2 samples from Macaé during the first outbreak of COVID-19, combined with clinical data and a molecular integrative analysis. First, phylogenomic analyses showed a high occurrence of viral introduction events and the establishment of local transmissions in Macaé, including the ingression and spread of the B.1.1.28 lineage in the municipality from June to August 2020. Second, SARS-CoV-2 mutations were identified in patients with distinct levels of COVID-19 severity. Third, molecular interactions of the mutated spike protein from three B.1.1.33 local samples and human ACE2 showed higher interactions than that of the wild-type spike protein from the ancestral virus. Altogether, these results elucidate the SARS-CoV-2 genomic profile in a strategic Brazilian city and further explore the functional aspects of SARS-CoV-2 with a characterization of emerging viral mutations associated with clinical data and the potential targets for drug development against SARS-CoV-2.

At the end of 2019 a new coronavirus surfaced in China, SARS-CoV-2, responsible for the ongoing pandemic. There is a need for novel and stable therapies to help patients of COVID-19. Drug repositioning is a strategy to quickly find medicines already used to treatment to another pathology. In this work, we used the PLpro as molecular target for it being responsible for cleaving other viral proteins and interfering with the immune system. In the Brazilian Pharmacopeia is described many different Active Pharmaceutical Ingredients (API) used in Brazil and the world. Using the in silico techniques of virtual screening, the top 44 API pass through Toxicity prediction, where 36 API prove to not be mutagenic. Using molecular weight, distance to the protein, and literature information 19 API go through prediction of chemical interactions, we determine the top 6 APIs with the best chance of interacting with the PLpro. With this result, we determine new possible API that will be tested in vitro to determine its ability to inhibit SARS-CoV-2’s PLpro, and could be readily made available to the infected populous.

At the end of 2019 a new coronavirus surfaced in China, SARS-CoV-2, responsible for the ongoing pandemic. There is a need for novel and stable therapies to help patients of COVID-19. Drug repositioning is a strategy to quickly find medicines already used to treatment to another pathology. In this work, we used the PLpro as molecular target for it being responsible for cleaving other viral proteins and interfering with the immune system. In the Brazilian Pharmacopeia is described many different Active Pharmaceutical Ingredients (API) used in Brazil and the world. Using the in silico techniques of virtual screening, the top 44 API pass through Toxicity prediction, where 36 API prove to not be mutagenic. Using molecular weight, distance to the protein, and literature information 19 API go through prediction of chemical interactions, we determine the top 6 APIs with the best chance of interacting with the PLpro. With this result, we determine new possible API that will be tested in vitro to determine its ability to inhibit SARS-CoV-2’s PLpro, and could be readily made available to the infected populous.