Catechin for COVID-19

The fast mutation of COVID-19 viruses still confuses us, and the mRNA vaccines do not inhibit the infection and may protect against the heavy disease. The infection mechanism is described with the protein-protein binding stereo structure; therefore, the infection strength of variants has been estimated from the protein-protein (S-RBD binding with ACE-2) interaction energy values calculated using a molecular mechanics program. The binding strength order was Alfa < Lambda < WT < FE.1 < XBB1.5 < EG.5 ≈ BQ.1 ≈ Alpha+E484K ≈ Omicron XBB.1.16 ≈ Epsilon, Iota < EG.5 < Delta plus ≈ Beta, Kappa B.1.621 ≈ KP.3 ≈ Kappa B.1.617.1 ≈ Delta B.1.517.2 < KP.2 < BA.2.86 ≈ JN.1 ≈ HV.1 ≈ BA.1 < BA.2. The mutation from acidic amino acid to basic amino acid strength the binding. The substitute size of amino acids causes the steric hindrance for the binding. The affinity level supports the infection strength. Various proposed infection inhibitors are quantitatively analyzed. TCA acids and natural polyphenols inhibit the binding of S-RBD to ACE-2. The cocktail dose of known medicines may enhance their performance. The inhibiting multiplication may be achieved using glycated compounds that bind glycoproteins and reduce glycoprotein activities.

A unique extreme acute breathing syndrome emerged in China and spread rapidly globally due to a newly diagnosed human coronavirus and declared a pandemic. COVID-19 was formally named by WHO, and the Global Committee on Taxonomy referred to it as extreme Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Currently there is no efficient method to control the extent of SARS-CoV-2 other than social distancing and hygiene activities. This study aims to present a simple medicinal strategy for combating fatal viral diseases like COVID-19 with minimum effort and intervention. Different Ayurveda medicines (Curcuma longa, green tea, andPiper nigrum) inhibit virus entrance and pathogen transmission while also enhancing immunity. Piperine (1-piperoylpiperidine), as well as curcumin, combine to create an intermolecular complex (ππ) that improves curcumin bioavailability by inhibiting glucuronidation of curcumin in the liver. The receptor-binding domains of the S-protein and also the angiotensin-converting enzyme 2 receptor of the recipient organism are directly occupied by curcumin and catechin, respectively, thereby preventing viruses from entering the cell. As a result, the infection will be tolerated by the animal host.

Coronavirus Disease 2019 (COVID-19) is a transmittable disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). The outbreak of the disease has affected the world in a negative manner. The development and on-going vaccination efforts has reduced the mortality rate in people with existing comorbidities and lowered virus transmission rate. However, there are still the needs for prescribed medicines that can be consumed by COVID-19 infected persons. Momordica charantia L. has been used in traditional medicines to treat various diseases including anti-diabetic and cancer. Pharmacological studies on Momordica charantia L. revealed that the plant stored many useful phytoconstituents that might be exploited for producing drug compounds to treat COVID-19. Nowadays, computational-aided drug methods are widely used in drug discovery process as it requires minimal compound design and improve the development pipeline. In this study, molecular docking of five phytochemicals from Momordica charantia L. were carried out against SARS-CoV-2 main protease (Mpro). The results obtained revealed that some of the phytochemicals showed a better dock score compared to the drug molnupiravir. Based on the dock score and the medicinal properties of each compound, it is suggested that these compounds can be further studied for potential drugs against COVID-19.

Objective: This study aims to elucidate the main compounds and mechanisms of action of Empon-empon (EE), a traditional Indonesian herb used for treating COVID-19 and atherosclerosis, utilizing an integrated network pharmacology and molecular docking approach. Methods: Active compounds in EE were obtained through the KNApSAcK, screening active compounds using parameters: oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. Compound-related target genes were collected from GeneCard, ChemBL, and Traditional Chinese Medicine Systems Pharmacology (TCMSP). Disease targets were obtained from the GeneCard database. The protein-protein interaction (PPI) network was built using STRING and visualized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using ShinyGO. Molecular docking analysis using Autodock Vina in PyRx. Results: We identified 18 main compounds in EE. PPI analysis obtained 5 central EE targets involved in treating COVID-19 and atherosclerosis, namely E1A Binding Protein P300 (EP300), Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1), SRC Proto-Oncogene (SRC), Estrogen Receptor 1 (ESR1), and RELA Proto-Oncogene (RELA). GO and KEGG analysis illustrated EE's pharmacological effects through pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling, including Coronavirus disease. Catechin and quercetin exhibited the strongest binding affinity to EP300; licarin B and delphinidin to HSP90AA1; epicatechin and delphinidin to SRC; galangin and ellagic acid to ESR1; and guaiacin and licarin B to RELA. Conclusion: This research provides a strong foundation regarding the main compound and mechanism action of EE in treating atherosclerosis and COVID-19, suggesting potential as a novel therapeutic agent.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

The existing literature supports the anti-inflammatory, antioxidant, and antiviral capacities of the polyphenol extracts derived from Geranium sanguineum L. These extracts exhibit potential in hindering viral replication by inhibiting enzymes like DNA polymerase and reverse transcriptase. The antiviral properties of G. sanguineum L. seem to complement its immunomodulatory effects, contributing to infection resolution. While preclinical studies on G. sanguineum L. suggest its potential effectiveness against COVID-19, there is still a lack of clinical evidence. Therefore, the polyphenols extracted from this herb warrant further investigation as a potential alternative for preventing and treating COVID-19 infections.

Guava (Psidium guajava L.) is a highly nutritious and economically important fruit. Although fruit peel is generally regarded as a waste, researchers believe that the peel of the guava is rich in bioactive constituents, even higher than the fruit's flesh. The present study aimed to estimate phenolic content (total phenolic and total flavonoid) and assess antioxidant properties of guava fruit peel (pink variety, cv Arka kiran) by 2,2-di (4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Ferric Reducing Antioxidant Potential (FRAP) assays at five different ripening stages (stage 1 to 5). The TPC and TFC assays were performed by Folin-Ciocalteu and aluminium chloride (AlCl3) methods, respectively. The molecular docking experiment between the major phenolic of guava peel, Catechin and the spike protein of SARS-CoV-2 was performed by the Dockthor online server. Results showed that the peel had high phenolic (highest TPC and TFC, 7307.3 mg gallic acid equivalent/g dry weight [DW] and 433.9 mg quercetin equivalent/g DW, respectively) and antioxidant values (highest DPPH, ABTS and FRAP values 4784.8, 206.6 and 2451 mg ascorbic acid equivalent/g DW, respectively) throughout all stages, although there was a gradual decline in the activity at the later stages. Furthermore, it was found that catechin had a strong binding affinity (-7.591 kcal mol-1) with the spike protein, in silico when compared with the control drug ceftazidime (-7.250 kcal mol-1). The overall outcome of our experiemnts revealed that guava peel could be explored for future pharmacological applications through in vivo studies, and the ‘green mixed with the yellow’ stage of ripening is optimum for such studies.

Abstract Background Coronavirus disease 2019 (COVID-19) is an infectious disease brought on by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global treat in early 2020. Despite worldwide research proving different medications used to treat COVID-19, the infection still affects the human race; we need to continue researching the virus to protect humanity and reduce the complications that some medications might cause. This study focuses on finding another promising therapeutic compound against SARS-CoV-2. Twenty-four (24) bioactive compounds were selected from the following African plants' Adansonia digitata L, Aframomum melegueta K. Schum, Ageratum conyzoides (L.) L, and Boswellia dalzielii, and Remdesivir was used as the control medication. The PubChem web server acquired the 3D structures of bioactive compounds in the plant and the control medication. The SARS-CoV-2 main protease (Mpro) crystal structure was obtained using the Protein Data Bank (PDB). Using the SwissADME web server, the bioactive compounds' drug-likeness was assessed, and AutoDock was employed for the molecular docking with the Mpro. The Proteins Plus and Protein–Ligand Interaction Profiler web servers were used to analyse the docked complexes. Furthermore, the admetSAR website was utilized to predict the ligands' absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Results Based on the drug-likeness screening, Rutin violated more than one of the Lipinski rules of five, while Remdesivir violated two. Molecular docking analysis results indicated that Catechin, Epicatechin, Vitexin, Quercetin, Kaempferol, Gamma-Sitosterol, and Kaur-16-ene exhibited a stronger binding affinity with Mpro, with binding scores of − 7.1, − 7.1, − 8.0, − 7.3, − 7.2, − 6.8, and − 6.5 kcal/mol, respectively, compared to Remdesivir's binding score of − 6.3 kcal/mol. Consequently, binding scores of bioactive compounds suggest their potential biological activity against the SARS-CoV-2 main protease. Additionally, these bioactive compounds exhibited favourable ADMET properties. Vitexin also has a plasma protein binding below 90%, a promising medication distribution feature. Conclusions This study shows that Catechin, Epicatechin, Vitexin, Quercetin, Kaempferol, Gamma-Sitosterol, and Kaur-16-ene have better binding affinities with Mpro than Remdesivir. Molecular dynamics simulation in vitro and in vivo investigation is required to support this study.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2019) etiological agent, which has a high contagiousness and is to blame for the outbreak of acute viral pneumonia, is the cause of the respiratory disease COVID-19. The use of natural products grew as an alternative treatment for various diseases due to the abundance of organic molecules with pharmacological properties. Many pharmaceutical studies have focused on investigating compounds with therapeutic potential. Therefore, this study aimed to identify potential antiviral compounds from a popular medicinal plant called Moringa oleifera Lam. against the spike, Mpro, ACE2, and RBD targets of SARS-CoV-2. For this, we use molecular docking to identify the molecules with the greatest affinity for the targets through the orientation of the ligand with the receptor in complex. For the best results, ADME-TOX predictions were performed to evaluate the pharmacokinetic properties of the compounds using the online tool pkCSM. The results demonstrate that among the 61 molecules of M. oleifera, 22 molecules showed promising inhibition results, where the compound ellagic acid showed significant molecular affinity (−9.3 kcal.mol−1) in interaction with the spike protein. These results highlight the relevance of investigating natural compounds from M. oleifera as potential antivirals against SARS-CoV-2; however, additional studies are needed to confirm the antiviral activity of the compounds.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

Aim: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins. Materials & methods: Several known antiviral natural compounds were subjected to molecular docking and MD simulation against SARS-CoV-2 Mpro, Helicase and Spike, including Delta and Omicron Spikes. Results: Of the docked ligands, 20 selected for each complex exhibited overall good binding affinities (-7.79 to -5.06 kcal/mol) with acceptable physiochemistry following Lipinski's rule. Finally, two best ligands from each complex upon simulation showed structural stability and compactness. Conclusion: Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A were identified as potential inhibitors of SARS-CoV-2 Mpro, Helicase and Spike, while Orientin and Obetrioside also showed good binding-affinities with Omicron Spike. Catechin and Neridienone A formed stable complexes with Delta Spike.

COVID-19 pandemic caused by the novel SARS-CoV-2 has impacted human livelihood globally. Strenuous efforts have been employed for its control and prevention; however, with recent reports on mutated strains with much higher infectivity, transmissibility, and ability to evade immunity developed from previous SARS-CoV-2 infections, prevention alternatives must be prepared beforehand in case. We have perused over 128 recent works (found on Google Scholar, PubMed, and ScienceDirect as of February 2023) on medicinal plants and their compounds for anti-SARS-CoV-2 activity and eventually reviewed 102 of them. The clinical application and the curative effect were reported high in China and in India. Accordingly, this review highlights the unprecedented opportunities offered by medicinal plants and their compounds, candidates as the therapeutic agent, against COVID-19 by acting as viral protein inhibitors and immunomodulator in (32 clinical trials and hundreds of in silico experiments) conjecture with modern science. Moreover, the associated foreseeable challenges for their viral outbreak management were discussed in comparison to synthetic drugs.

Natural products and plant extracts exhibit many biological activities, including that related to the defense mechanisms against parasites. Many studies have investigated the biological functions of secondary metabolites and reported evidence of antiviral activities. The pandemic emergencies have further increased the interest in finding antiviral agents, and efforts are oriented to investigate possible activities of secondary plant metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection. In this review, we performed a comprehensive analysis of studies through in silico and in vitro investigations, also including in vivo applications and clinical trials, to evaluate the state of knowledge on the antiviral activities of secondary metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection, with a particular focus on natural compounds present in food plants. Although some of the food plant secondary metabolites seem to be useful in the prevention and as a possible therapeutic management against SARS-CoV-2, up to now, no molecules can be used as a potential treatment for COVID-19; however, more research is needed.

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.

Graphical AbstractInhibition of proteolytic and deubiquitinase activity of SARS-CoV-2 PLpro enzyme by phytochemicals.

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 and became a pandemic in a critically short time. Phenolic secondary metabolites attracted much attention from the pharmaceutical industries for their easily accessible natural sources and proven antiviral activity. In our mission, a metabolomics study of the Garcinia cambogia Roxb. fruit rind was performed using LC-HRESIMS to investigate its chemical profile, especially the polar aspects, followed by a detailed phytochemical analysis, which led to the isolation of eight known compounds. Using spectrometric techniques, the isolated compounds were identified as quercetin, amentoflavone, vitexin, rutin, naringin, catechin, p-coumaric, and gallic acids. The antiviral activities of the isolated compounds were investigated using two assays; the 3CL-Mpro enzyme showed that naringin had a potent effect with IC50 16.62 μg/mL, followed by catechin and gallic acid (IC50 26.2, 30.35 μg/mL, respectively), while the direct antiviral inhibition effect of naringin confirmed the potency with an EC50 of 0.0169 μM. To show the molecular interaction, in situ molecular docking was carried out using a COVID-19 protease enzyme. Both biological effects and docking studies showed the hydrophobic interactions with Gln 189 or Glu 166, per the predicated binding pose of the isolated naringin.

Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.

The first cases of COVID-19, which is caused by the SARS-CoV-2, were reported in December 2019. The vertiginous worldwide expansion of SARS-CoV-2 caused the collapse of health systems in several countries due to the high severity of the COVID-19. In addition to the vaccines, the search for active compounds capable of preventing and/or fighting the infection has been the main direction of research. Since the beginning of this pandemic, some evidence has highlighted the importance of a phenolic-rich diet as a strategy to reduce the progression of this disease, including the severity of the symptoms. Some of these compounds (e.g., curcumin, gallic acid or quercetin) already showed capacity to limit the infection of viruses by inhibiting entry into the cell through its binding to protein Spike, regulating the expression of angiotensin-converting enzyme 2, disrupting the replication in cells by inhibition of viral proteases, and/or suppressing and modulating the host’s immune response. Therefore, this review intends to discuss the most recent findings on the potential of phenolics to prevent SARS-CoV-2.