Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection.
Ontology highlight
ABSTRACT:
SUBMITTER: Cheng FJ
PROVIDER: S-EPMC8401008 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.
| S-EPMC7354438 | biostudies-literature
Project description:ACE2 is a major receptor for cellular entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2 binding, strategies to flexibly and sufficiently reduce ACE2 levels for the prevention of SARS-CoV-2 infection have not been explored. Here, we reveal vitamin C (VitC) administration as a potent strategy to prevent SARS-CoV-2 infection. VitC reduces ACE2 protein levels in a dose-dependent manner, while even a partial reduction in ACE2 levels can greatly inhibit SARS-CoV-2 infection. Further studies reveal that USP50 is a crucial regulator of ACE2 levels. VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination of ACE2 at Lys788 and subsequent degradation of ACE2 without affecting its transcriptional expression. Importantly, VitC administration reduces host ACE2 levels and greatly blocks SARS-CoV-2 infection in mice. This study reveals that ACE2 protein levels are down-regulated by an essential nutrient, VitC, thereby enhancing protection against infection of SARS-CoV-2 and its variants.
| S-SCDT-10_15252-EMBR_202256374 | biostudies-other
Project description:Leucoefdin an important constituent of various fruits such as banana, raspberry, etc. was explored to target MPro protease of SARS Co-V 2. Ligand was found to bind at active site of MPro with large negative binding energies in molecular docking and simulation study. The docking results showed that Leucoefdin interacted with the MPro by forming hydrogen bonds, at Leu 141, His163, His 164, and Glu 166. Other non-bonded interactions were seen at Met49, Pro52, Tyr54, Phe140, Leu141, Cys145 and Met165. Results of Leucoefdin was in coherence with the recently reported MPro protease-inhibitor complex. It even displayed better binding energies (kcal/mol) in HTVS (-6.28), SP (-7.28), XP (-9.29) and MMGBSA (-44.71) as compared to the reference ligand [HTVS (-4.87), SP (-6.79), XP (-5.75) and MMGBSA (-47.76)]. Leucoefdin-MPro complex on molecular dynamic simulation showed initial fluctuations in RMSD plot for a certain period and attained equilibrium which remained stable during entire simulation for 150 ns. RMSF of protein showed less secondary structure fluctuations and a greater number of H-bond formation with Leucoefdin during 150 ns simulation. Post simulation MMGBSA analysis showed binding energy of -45.98 Kcal/mol. These findings indicated the potential of Leucoefdin as lead compound in R&D for drug discovery and development against SARS CoV-2.Communicated by Ramaswamy H. Sarma.
| S-EPMC7309301 | biostudies-literature
Project description:Propolis, a resinous material produced by honey bees from plant exudates, has long been used in traditional herbal medicine and is widely consumed as a health aid and immune system booster. The COVID-19 pandemic has renewed interest in propolis products worldwide; fortunately, various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds. SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. This mechanism involves PAK1 overexpression, which is a kinase that mediates coronavirus-induced lung inflammation, fibrosis, and immune system suppression. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. In pre-clinical studies, propolis promoted immunoregulation of pro-inflammatory cytokines, including reduction in IL-6, IL-1 beta and TNF-?. This immunoregulation involves monocytes and macrophages, as well as Jak2/STAT3, NF-kB, and inflammasome pathways, reducing the risk of cytokine storm syndrome, a major mortality factor in advanced COVID-19 disease. Propolis has also shown promise as an aid in the treatment of various of the comorbidities that are particularly dangerous in COVID-19 patients, including respiratory diseases, hypertension, diabetes, and cancer. Standardized propolis products with consistent bioactive properties are now available. Given the current emergency caused by the COVID-19 pandemic and limited therapeutic options, propolis is presented as a promising and relevant therapeutic option that is safe, easy to administrate orally and is readily available as a natural supplement and functional food.
| S-EPMC7430291 | biostudies-literature
Project description:Because of the uninterrupted spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious disease (COVID-19) with substantial illness and mortality rates, there is an urgent requirement of suitable antiviral agent/therapy to control this pandemic, but not yet established. The primary cause of SARS-CoV-2 infection is the crosstalk between the SARS-CoV-2 and host surface receptor protein, human angiotensin-converting enzyme 2 (hACE2), prior to cellular entry. Hence, blocking at the initial stage of virus entry could be a promising strategy/therapy to combat the SARS-CoV-2 infection. Many drugs as SARS-CoV-2 blocker have been proposed. Among them, peptide-based antivirals are one. This Viewpoint discusses the potential antiviral role and feasibility of two classes of peptides for prevention of SARS-CoV-2 infection, where (1) a designed peptide (replication of virus binding domain of hACE2), and (2) antimicrobial peptides (AMPs; natural and first line host defense peptide), both may reduce virus load into the host cell by blocking cellular surface receptors and/or disruption of virus cell membrane at the stage of virus entry. These finding may provide a novel antiviral therapy against COVID-19, which might control the current global health crisis.
| S-EPMC7393772 | biostudies-literature
Project description:The pandemic burden caused by the SARS-CoV-2 coronavirus constitutes a global public health emergency. Increasing understanding about predisposing factors to infection and severity is now a priority. Genetic, metabolic, and environmental factors can play a crucial role in the course and clinical outcome of COVID-19. We aimed to investigate the putative relationship between genetic factors associated to obesity, metabolism and lifestyle, and the presence and severity of SARS-CoV-2 infection. A total of 249 volunteers (178 women and 71 men, with mean and ± SD age of 49 ± 11 years) characterized for dietary, lifestyle habits and anthropometry, were studied for presence and severity of COVID-19 infection, and genotyped for 26 genetic variants related to obesity, lipid profile, inflammation, and biorhythm patterns. A statistically significant association was found concerning a protective effect of APOE rs7412 against SARS-CoV-2 infection (p = 0.039; OR 0.216; CI 0.084, 0.557) after correction for multiple comparisons. This protective effect was also ascribed to the APOɛ2 allele (p = 0.001; OR 0.207; CI 0.0796, 0.538). The genetic variant rs7412 resulting in ApoE2, genetic determinant of lipid and lipoprotein levels, could play a significant role protecting against SARS-CoV-2 infection.
| S-EPMC9065660 | biostudies-literature
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other
Project description:BackgroundThe present pandemic situation due to coronavirus has led to the search for newer prevention, diagnostic, and treatment methods. The onset of the corona infection in a human results in acute respiratory illness followed by death if not diagnosed and treated with suitable antiretroviral drugs. With the unavailability of the targeted drug treatment, several repurposed drugs are being used for treatment. However, the side-effects of the drugs urges us to move to a search for newer synthetic- or phytochemical-based drugs. The present study investigates the use of various phytochemicals virtually screened from various plant sources in Western Ghats, India, and subsequently molecular docking studies were performed to identify the efficacy of the drug in retroviral infection particularly coronavirus infection.ResultsOut of 57 phytochemicals screened initially based on the structural and physicochemical properties, 39 were effectively used for the docking analysis. Finally, 5 lead compounds with highest hydrophobic interaction and number of H-bonds were screened. Results from the interaction analysis suggest Piperolactam A to be pocketed well with good hydrophobic interaction with the residues in the binding region R1. ADME and toxicity profiling also reveals Piperolactam A with higher LogS values indicating higher permeation and hydrophilicity. Toxicity profiling suggests that the 5 screened compounds to be relatively safe.ConclusionThe in silico methods used in this study suggests that the compound Piperolactam A to be the most effective inhibitor of S-protein from binding to the GRP78 receptor. By blocking the binding of the S-protein to the CS-GRP78 cell surface receptor, they can inhibit the binding of the virus to the host.Supplementary informationThe online version contains supplementary material available at 10.1186/s43088-021-00095-x.
| S-EPMC7841026 | biostudies-literature
Project description:The outbreak of novel coronavirus strain (Covid-19) with a high pandemic threat has predict grave public health and economic concerns. This virus, originating from the Wuhan region in China has spread worldwide affecting millions with no registered persuasive targeted therapy. In this paper, we analyze the three important proteins encoded by the virus, envelope protein 5 × 29, RNA binding nucleocapsid protein 1SSK, and spike glycoprotein 6ACD, for an effective virion accumulation, and remdesivir was the first drug approved by the FDA and EMA for the treatment of COVID-19 cases that require hospitalization, there is still much controversy about its efficacy and also an alternative for novel phytochemicals, deoxynojirimycin, trigoneoside IB, and octanoic acid. The in-silico evaluations were conducted using the PyRx virtual screening tools which lead to the target based on high binding affinity. Trigoneoside IB, derived from Trigonella foenum-graecum (Fenugreek), showed the highest binding affinity and stable interaction with the amino acid residues present in active sites of Covid-19 proteins. Meanwhile, the other two compounds derived from Morus alba (Mulberry) and Morinda citrifolia (Noni), as well as the anti-HIV remdesivir drug exhibited good binding affinity and favorable ADME properties. Thereby offering scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against the Covid-19 proteins.
| S-EPMC8110638 | biostudies-literature
Project description:The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019, and its global dissemination became the coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) on 11 March 2020. In patients undergoing immunotherapy, the effect and path of viral infection remain uncertain. In addition, viral-infected mice and humans show T-cell exhaustion, which is identified after infection with SARS-CoV-2. Notably, they regain their T-cell competence and effectively prevent viral infection when treated with anti-PD-1 antibodies. Four clinical trials are officially open to evaluate anti-PD-1 antibody administration's effectiveness for cancer and non-cancer individuals influenced by COVID-19 based on these findings. The findings may demonstrate the hypothesis that a winning strategy to combat SARS-CoV-2 infection could be the restoration of exhausted T-cells. In this review, we outline the potential protective function of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 therapy.
| S-EPMC8315943 | biostudies-literature