The emergence of viral pneumonia caused by a novel coronavirus (CoV), known as the 2019 novel coronavirus (2019-nCoV), resulted in a contagious acute respiratory infectious disease in December 2019 in Wuhan, Hubei Province, China. Its alarmingly quick transmission to many countries across the world and a considerable percentage of morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, 2020. The perceived risk of infection has led many research groups to study COVID-19 from different aspects. In this literature review, the phylogenetics and taxonomy of COVID-19 coronavirus, epidemiology, and respiratory viruses similar to COVID-19 and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID-19 disease. Additionally, since phytochemicals play an essential role in complementary therapies for viral infections, we summarized different bioactive natural products against the mentioned respiratory viruses with a focus on influenza A, SARS-CoV, MERS, and COVID-19.Based on current literature, 130 compounds have antiviral potential, and of these, 94 metabolites demonstrated bioactivity against coronaviruses. Interestingly, these are classified in different groups of natural products, including alkaloids, flavonoids, terpenoids, and others. Most of these compounds comprise flavonoid skeletons. Based on our survey, xanthoangelol E (88), isolated from Angelica keiskei (Miq.) Koidz showed inhibitory activity against SARS-CoV PLpro with the best IC50 value of 1.2 μM. Additionally, hispidulin (3), quercetin (6), rutin (8), saikosaponin D (36), glycyrrhizin (47), and hesperetin (55) had remarkable antiviral potential against different viral infections. Among these compounds, quercetin (6) exhibited antiviral activities against influenza A, SARS-CoV, and COVID-19 and this seems to be a highly promising compound. In addition, our report discusses the obstacles and future perspectives to highlight the importance of developing screening programs to investigate potential natural medicines against COVID-19.
Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers.
Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased. Worldwide collaborative efforts from scientists are underway to determine a therapy to treat COVID-19 infections and reduce mortality rates. Since herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs), this in silico evaluation was performed for identifying potential natural compounds with promising inhibitory activities against COVID-19. Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method for discovering novel drug candidates as potential COVID-19 main protease (Mpro) inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 Mpro. In this study, the Glide docking program was applied for high throughput virtual screening. Also, Extra precision (XP) has been used following the induced-fit docking (IFD) approach. The ADME properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Also, molecular dynamics (MD) simulations were conducted for a virtual complex of the best scoring compound with COVID-19 protease. Results: Nineteen compounds were introduced as new potential inhibitors. Compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamide showed a strong binding affinity (-11.5 kcal/mol) to the COVID-19 Mpro comparing to peramivir (-9.8 kcal/mol) as a positive control. Conclusions: Based on these findings, nineteen compounds were proposed as possible new COVID-19 inhibitors, of which ZINC08765174 had a high affinity to Mpro. Furthermore, the promising ADME properties of the selected compounds emphasize their potential as attractive candidates for the treatments of COVID-19.
Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness that was unknown in the human before. Its alarmingly quick transmission to many countries across the world resulted in a worldwide health emergency. It has caused a notable percentage of morbidity and mortality. Therefore, an imminent need for drugs to combat this disease has been increased. Global collaborative efforts from scientists are underway to find a therapy to treat infections and reduce death cases. Herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs).Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method on the discovery of novel drug candidates as the COVID-19 main protease inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 main protease. In this study, the Glide docking program was applied for high throughput virtual screening. Extra precision (XP) and in a combination of Prime module, induced-fit docking (IFD) approach was also used. Additionally, the ADME properties of all compounds were analyzed, and the final selection was carried out based on the Lipinski rule of five. Results: The nineteen compounds were selected and introduced as new potential inhibitors. The compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamide) showed a strong binding affinity (-11.5 kcal/mol) to the crucial residues of COVID-19 main protease comparing to peramivir (-9.8 kcal/mol) as a positive control.Conclusions: The excellent ADME properties proposed the opportunity of this compound to be a promising candidate for the treatment of COVID-19.
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