Speciophylline for COVID-19

The COVID-19 pandemic stimulated the widespread use of traditional medicinal plants in Brazil, particularly in regions with limited access to healthcare and approved therapies. In this context, medicinal plants became accessible alternatives for symptom management and disease prevention, highlighting the value of traditional health systems as sources of biologically relevant species for further investigation. This study documented medicinal plants used to prevent and treat COVID-19 in São Luís, Maranhão, Brazil, and evaluated the inhibitory activity of Uncaria tomentosa (Willd. Ex Schult)extracts, the most frequently cited species, against the SARS-CoV-2 RBD:ACE2 interaction. An ethnopharmacological survey was initially conducted with 400 participants between November 2022 and March 2023 where a total of 38 medicinal ethnospecies were reported, with an overall prevalence of medicinal plant use of 22.75%. Considering that aqueous preparations were the predominant form of use reported by participants, both aqueous and ethanolic extracts were prepared from the stem bark and leaves of U. tomentosa and evaluated in an in vitro Spike (RBD) inhibition assay. The highest inhibitory activity was observed for stem bark extracts of U. tomentosa, which achieved 98.09% inhibition for the ethanolic extract and 73.40% for the aqueous extract. Preparations obtained from the leaves showed lower activity, with inhibition values of 41.12% and 19.74%, respectively. Chemical profiling was performed by LC-MS/MS combined with molecular networking. Chemical analysis enabled the annotation of oxindole alkaloids and flavonoids previously reported in the literature as exhibiting relevant biological activities in models of viral infections. These findings highlight the ethnopharmacological relevance of U. tomentosa, support its potential as a source of bioactive metabolites, and reinforce the value of ethnopharmacological approaches in identifying promising species for further biological investigation.

<ns3:p>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.</ns3:p>

Abstract Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization raised concerns about the Omicron variant, which emerged in South Africa during a surge in COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against Omicron, leading to clinical trials for combating infection by the mutated virus. The absence of suitable pharmaceuticals has led scientists and clinicians to search for alternative and supplementary therapies, including dietary patterns, to reduce the effect of mutated strains. Main body This review analyzed Coronavirus aetiology, epidemiology, and natural products for combating Omicron. Although the literature search did not include keywords related to in silico or computational research, in silico investigations were emphasized in this study. Molecular docking was implemented to compare the interaction between natural products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking results suggest that DGCG may bind to the ACE2 receptor three times more effectively than standard chloroquine. Conclusion The emergence of the Omicron variant has highlighted the need for alternative therapies to reduce the impact of mutated strains. The current review suggests that natural products such as DGCG may be effective in binding to the ACE2 receptor and combating the Omicron variant, however, further research is required to validate the results of this study and explore the potential of natural products to mitigate COVID-19. Graphical abstract

Over 750 million cases of COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), have been reported since the onset of the global outbreak. The need for effective treatments has spurred intensive research for therapeutic agents based on pharmaceutical repositioning or natural products. In light of prior studies asserting the bioactivity of natural compounds of the autochthonous Peruvian flora, the present study focuses on the identification SARS-CoV-2 Mpro main protease dimer inhibitors. To this end, a target-based virtual screening was performed over a representative set of Peruvian flora-derived natural compounds. The best poses obtained from the ensemble molecular docking process were selected. These structures were subjected to extensive molecular dynamics steps for the computation of binding free energies along the trajectory and evaluation of the stability of the complexes. The compounds exhibiting the best free energy behaviors were selected for in vitro testing, confirming the inhibitory activity of Hyperoside against Mpro, with a Ki value lower than 20 µM, presumably through allosteric modulation.