Dietary polyphenols mitigate SARS-CoV-2 main protease (Mpro)-Molecular dynamics, molecular mechanics, and density functional theory investigations.

The recent evolution of the SARS-like Coronavirus has ravaged the world. The deadly virus has claimed over millions of lives across the world and hence highlights the need to develop effective therapeutic drugs to contain the disease posed by this parasite. In this study, the inhibitory potential of fifty (50) dietary polyphenols against Coronavirus (SARS-CoV-2) main protease (Mpro) was conducted using the Autodock Vina Molecular docking tool. In the virtual screening process, the binding affinity of Remdesivir (-7.7 kcal/mol) currently used to treat COVID-19 patients was set as the cut-off value to screen out less probable inhibitors. Ellagic acid, Kievitone, and Punicalin were the only promising ligands with binding affinities (-8.9 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol respectively) lower than the set cut-off value. Furthermore, we validated Ellagic acid and Kievitone efficacy by subjecting them to molecular dynamics simulation and further stability was assessed at the molecular mechanics and quantum levels. The overall analysis indicates both compounds demonstrate higher stability and inhibitory potential to bind to the crucial His41 and Cys145 catalytic dyad of Mpro than the standard drug. However, further analysis of punicalin after evaluating its docking score was not conducted as the ligand pharmacokinetics properties suggests it could pose serious adverse effect to the health of participants in clinical trials. Hence, we employed a more safe approach by filtering out the compound during this study. Conclusively, while Ellagic acid and kievitone polyphenolic compounds have been demonstrated to be promising under this in silico research, further studies are needed to substantiate their clinical relevance.

A secondary approach with conventional medicines and supplements to recuperate current COVID-19 status.

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.

In silico investigation of saponins and tannins as potential inhibitors of SARS-CoV-2 main protease (Mpro).

It is no longer news that a novel strain of coronavirus named SARS-CoV-2 is ravaging the health sector worldwide, several attempts have been made to curtail this pandemic via repurposing of old drugs but at the present, available drugs are not adequately effective. Over the years, plant phytochemicals are increasingly becoming alternative sources of antimicrobial agents with novel mechanisms of action and limited side effects compared to synthetic drugs. Isolated saponins and tannins were evaluated for antiviral activity against SARS-CoV-2 (Mpro) via Molecular Docking and it was observed that a handsome number of the phytochemicals had binding affinities much better than Remdesivir, Dexamethasone, and N3 inhibitor which were used as the standards in this study. Further investigation of drug-likeness, ADMET profile, PASS profile, oral bioavailability, bioactivity, binding mode, and molecular interactions of these phytochemicals revealed that binding affinity alone is not enough to justify the potency of a molecule in the drug discovery process, as only 4 among the screened compounds passed all the analyses and are identified as potential inhibitors of SARS-CoV-2 (Mpro). This preliminary study thereby recommends Ellagic acid (- 8.4 kcal/mol), Arjunic Acid (- 8.1 kcal/mol), Theasapogenol B (- 8.1 kcal/mol), and Euscaphic Acid (- 8.0 kcal/mol) as potential inhibitors of SARS-CoV-2 (Mpro) with better pharmacokinetics and bioavailability compared to Remdesivir which is currently used compassionately.