Epigallocatechin Gallate Inhibits the Uridylate-Specific Endoribonuclease Nsp15 and Efficiently Neutralizes the SARS-CoV-2 Strain.
21 May 2021-Journal of Agricultural and Food Chemistry (American Chemical Society (ACS))-Vol. 69, Iss: 21, pp 5948-5954
TL;DR: In this paper, natural compounds, epigallocatechin gallate (EGCG), baicalin, and quercetin, were identified as potential inhibitors against Nsp15 from SARS-CoV-2.
Abstract: SARS-CoV-2, the coronavirus strain that initiated the COVID-19 pandemic, and its subsequent variants present challenges to vaccine development and treatment. As the coronavirus evades the host innate immune response at the initial stage of infection, the disease can have a long nonsymptomatic period. The uridylate-specific endoribonuclease Nsp15 processes the viral genome for replication and cleaves the polyU sequence in the viral RNA to interfere with the host immune system. This study screened natural compounds in vitro to identify inhibitors against Nsp15 from SARS-CoV-2. Three natural compounds, epigallocatechin gallate (EGCG), baicalin, and quercetin, were identified as potential inhibitors. Potent antiviral activity of EGCG was confirmed in plaque reduction neutralization tests with a SARS-CoV-2 strain (PRNT50 = 0.20 μM). Because the compound has been used as a functional food ingredient due to its beneficial health effects, we theorize that this natural compound may help inhibit viral replication while minimizing safety issues.
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TL;DR: A wide range of natural products can be considered promising anti-COVID-19 or anti-lung cancer agents have gained widespread attention, including natural products as monotherapy for the treatment of SARS-CoV-2 (ginkgolic acid, shiraiachrome A, resveratrol, and baicalein) or lung cancer (daurisoline, graveospene A, deguelin, and erianin) as mentioned in this paper.
Abstract: As a public health emergency of international concern, the highly contagious coronavirus disease 2019 (COVID-19) pandemic has been identified as a severe threat to the lives of billions of individuals. Lung cancer, a malignant tumor with the highest mortality rate, has brought significant challenges to both human health and economic development. Natural products may play a pivotal role in treating lung diseases. We reviewed published studies relating to natural products, used alone or in combination with US Food and Drug Administration-approved drugs, active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lung cancer from 1 January 2020 to 31 May 2021. A wide range of natural products can be considered promising anti-COVID-19 or anti-lung cancer agents have gained widespread attention, including natural products as monotherapy for the treatment of SARS-CoV-2 (ginkgolic acid, shiraiachrome A, resveratrol, and baicalein) or lung cancer (daurisoline, graveospene A, deguelin, and erianin) or in combination with FDA-approved anti-SARS-CoV-2 agents (cepharanthine plus nelfinavir, linoleic acid plus remdesivir) and anti-lung cancer agents (curcumin and cisplatin, celastrol and gefitinib). Natural products have demonstrated potential value and with the assistance of nanotechnology, combination drug therapies, and the codrug strategy, this “natural remedy” could serve as a starting point for further drug development in treating these lung diseases.
50 citations
TL;DR: In this paper, the effects of flavonoids on various key SARS-CoV-2 targets were analyzed and an analysis of the structure-activity relationships for the same was presented.
Abstract: The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.
39 citations
TL;DR: In this paper, the authors discuss the immune responses to SARS-CoV-2, how COVID-19 vaccines elicit protective immune responses, gut dysbiosis involvement in inefficacy and adverse effects of COVID19 vaccines and the modulation of the gut microbiota by functional foods to improve COVID -19 vaccine immunisations.
19 citations
TL;DR: In this paper , the authors discuss the current findings in the development of small molecules for COVID-19 treatment, including their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies.
Abstract: Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and M pro , interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.
16 citations
TL;DR: A review of the antiviral activity of plant-derived natural products against RNA viruses, with a focus on compounds targeting specific stages of the viral life cycle, is presented in this paper .
Abstract: Abstract There is a need for new effective antivirals, particularly in response to the development of antiviral drug resistance and emerging RNA viruses such as SARS-CoV-2. Plants are a significant source of structurally diverse bioactive compounds for drug discovery suggesting that plant-derived natural products could be developed as antiviral agents. This article reviews the antiviral activity of plant-derived natural products against RNA viruses, with a focus on compounds targeting specific stages of the viral life cycle. A range of plant extracts and compounds have been identified with antiviral activity, often against multiple virus families suggesting they may be useful as broad-spectrum antiviral agents. The antiviral mechanism of action of many of these phytochemicals is not fully understood and there are limited studies and clinical trials demonstrating their efficacy and toxicity in vivo. Further research is needed to evaluate the therapeutic potential of plant-derived natural products as antiviral agents.
14 citations
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