Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 405
Filter
1.
Virology ; 570: 18-28, 2022 May.
Article in English | MEDLINE | ID: covidwho-1839384

ABSTRACT

The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.


Subject(s)
Biological Products , COVID-19 , Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases , Humans , Molecular Docking Simulation , Pandemics , Peptide Hydrolases , Protease Inhibitors/pharmacology , SARS-CoV-2
2.
Microb Pathog ; 165: 105497, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1814971

ABSTRACT

The study focuses on identifying and screening natural products (NPs) based on their structural similarities with chemical drugs followed by their possible use in first-line treatment to COVID-19 infection. In the present study, the in-house natural product libraries, consisting of 26,311 structures, were screened against potential targets of SARS-CoV-2 based on their structural similarities with the prescribed chemical drugs. The comparison was based on molecular properties, 2 and 3-dimensional structural similarities, activity cliffs, and core fragments of NPs with chemical drugs. The screened NPs were evaluated for their therapeutic effects based on their predicted in-silico pharmacokinetic and pharmacodynamics properties, binding interactions with the appropriate targets, and structural stability of the bound complex using molecular dynamics simulations. The study yielded NPs with significant structural similarities to synthetic drugs currently used to treat COVID-19 infections. The study proposes the probable biological action of the selected NPs as Anti-retroviral protease inhibitors, RNA-dependent RNA polymerase inhibitors, and viral entry inhibitors.


Subject(s)
Biological Products , COVID-19 , Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2
3.
Daru ; 30(1): 191-210, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1813906

ABSTRACT

OBJECTIVES: The recent emergence of the COVID-19 pandemic (caused by SARS-CoV-2) and the experience of its unprecedented alarming toll on humanity have shone a fresh spotlight on the weakness of global preparedness for pandemics, significant health inequalities, and the fragility of healthcare systems in certain regions of the world. It is imperative to identify effective drug treatments for COVID-19. Therefore, the objective of this review is to present a unique and contextualised collection of antiviral natural plants or remedies from the West African sub-region as existing or potential treatments for viral infections, including COVID-19, with emphasis on their mechanisms of action. EVIDENCE ACQUISITION: Evidence was synthesised from the literature using appropriate keywords as search terms within scientific databases such as Scopus, PubMed, Web of Science and Google Scholar. RESULTS: While some vaccines and small-molecule drugs are now available to combat COVID-19, access to these therapeutic entities in many countries is still quite limited. In addition, significant aspects of the symptomatology, pathophysiology and long-term prognosis of the infection yet remain unknown. The existing therapeutic armamentarium, therefore, requires significant expansion. There is evidence that natural products with antiviral effects have been used in successfully managing COVID-19 symptoms and could be developed as anti-COVID-19 agents which act through host- and virus-based molecular targets. CONCLUSION: Natural products could be successfully exploited for treating viral infections/diseases, including COVID-19. Strengthening natural products research capacity in developing countries is, therefore, a key strategy for reducing health inequalities, improving global health, and enhancing preparedness for future pandemics.


Subject(s)
Biological Products , COVID-19 , Plants, Medicinal , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Pandemics , SARS-CoV-2
4.
MMW Fortschr Med ; 164(8): 28-29, 2022 04.
Article in German | MEDLINE | ID: covidwho-1800280
5.
Antimicrob Agents Chemother ; 66(2): e0158121, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1799247

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against human CoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and Middle East respiratory syndrome coronavirus (MERS-CoV), and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane, as demonstrated by cryoelectron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2-contaminated surfaces.


Subject(s)
Biological Products , COVID-19 , Middle East Respiratory Syndrome Coronavirus , Antiviral Agents/pharmacology , Biological Products/pharmacology , Cryoelectron Microscopy , Humans , SARS-CoV-2
6.
Curr Drug Targets ; 23(4): 420-436, 2022.
Article in English | MEDLINE | ID: covidwho-1799012

ABSTRACT

Chrysin (a flavonoid) has shown various promising pharmacological activities viz. anticancer, anti-diabetic, immune-modulation, antidepressant, and anti-asthmatic. Additionally, it exhibited potential protective effects against various toxins on different organs like the liver, brain, kidney, and heart. A multitude of studies have been conducted to explore the possible targets for its possible mechanism of action. However, its therapeutic applications have been limited due to its poor oral bioavailability. The major reason for its poor bioavailability is its extensive first-pass metabolism. A critical review of the pharmacological properties of chrysin and its associated molecular targets has not been discussed as yet comprehensively. Therefore, the emphasis of the present work is to provide an in-depth understanding of molecular targets accountable for the pharmacological actions of chrysin. Moreover, a schematic diagram was made for the first time to represent the comprehensive pharmacokinetic properties of chrysin, which helps to understand the biopharmaceutical aspect for its successful delivery. An in-depth understanding of the biopharmaceutical properties of chrysin will help in adopting a suitable formulation approach to overcome poor oral bioavailability. Additionally, it facilitates to study the possible pharmacokinetic interactions of chrysin with other drugs. Hence, we found that chrysin is a miraculous natural agent with myriad therapeutic properties, and its benefit can be exploited with an in-depth understanding of molecular targets, pharmacological actions, and biopharmaceutical attributes.


Subject(s)
Biological Products , Flavonoids , Biological Availability , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Pharmaceutical Preparations
7.
Molecules ; 27(9)2022 Apr 19.
Article in English | MEDLINE | ID: covidwho-1792595

ABSTRACT

The marine environment presents a favorable avenue for potential therapeutic agents as a reservoir of new bioactive natural products. Due to their numerous potential pharmacological effects, marine-derived natural products-particularly marine peptides-have gained considerable attention. These peptides have shown a broad spectrum of biological functions, such as antimicrobial, antiviral, cytotoxic, immunomodulatory, and analgesic effects. The emergence of new virus strains and viral resistance leads to continuing efforts to develop more effective antiviral drugs. Interestingly, antimicrobial peptides (AMPs) that possess antiviral properties and are alternatively regarded as antiviral peptides (AVPs) demonstrate vast potential as alternative peptide-based drug candidates available for viral infection treatments. Hence, AVPs obtained from various marine organisms have been evaluated. This brief review features recent updates of marine-derived AVPs from 2011 to 2021. Moreover, the biosynthesis of this class of compounds and their possible mechanisms of action are also discussed. Selected peptides from various marine organisms possessing antiviral activities against important human viruses-such as human immunodeficiency viruses, herpes simplex viruses, influenza viruses, hepatitis C virus, and coronaviruses-are highlighted herein.


Subject(s)
Biological Products , Virus Diseases , Viruses , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Humans , Peptides/pharmacology , Peptides/therapeutic use , Virus Diseases/drug therapy
8.
Bioorg Med Chem Lett ; 66: 128732, 2022 06 15.
Article in English | MEDLINE | ID: covidwho-1783213

ABSTRACT

In the past two years, the COVID-19 pandemic has caused over 5 million deaths and 250 million infections worldwide. Despite successful vaccination efforts and emergency approval of small molecule therapies, a diverse range of antivirals is still needed to combat the inevitable resistance that will arise from new SARS-CoV-2 variants. The main protease of SARS-CoV-2 (Mpro) is an attractive drug target due to the clinical success of protease inhibitors against other viruses, such as HIV and HCV. However, in order to combat resistance, various chemical scaffolds need to be identified that have the potential to be developed into potent inhibitors. To this end, we screened a high-content protease inhibitor library against Mproin vitro, in order to identify structurally diverse compounds that could be further developed into antiviral leads. Our high-content screening efforts retrieved 27 hits each with > 50% inhibition in our Mpro FRET assay. Of these, four of the top inhibitor compounds were chosen for follow-up due to their potency and drugability (Lipinski's rules of five criteria): anacardic acid, aloesin, aloeresin D, and TCID. Further analysis via dose response curves revealed IC50 values of 6.8 µM, 38.9 µM, 125.3 µM, and 138.0 µM for each compound, respectively. Molecular docking studies demonstrated that the four inhibitors bound at the catalytic active site of Mpro with varying binding energies (-7.5 to -5.6 kcal/mol). Furthermore, Mpro FRET assay kinetic studies demonstrated that Mpro catalysis is better represented by a sigmoidal Hill model than the standard Michaelis-Menten hyperbola, indicating substantial cooperativity of the active enzyme dimer. This result suggests that the dimerization interface could be an attractive target for allosteric inhibitors. In conclusion, we identified two closely-related natural product compounds from the Aloe plant (aloesin and aloeresin D) that may serve as novel scaffolds for Mpro inhibitor design and additionally confirmed the strongly cooperative kinetics of Mpro proteolysis. These results further advance our knowledge of structure-function relationships in Mpro and offer new molecular scaffolds for inhibitor design.


Subject(s)
Aloe , Biological Products , COVID-19 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biological Products/pharmacology , Coronavirus 3C Proteases , Humans , Kinetics , Molecular Docking Simulation , Pandemics , Prospective Studies , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , SARS-CoV-2
9.
Molecules ; 27(7)2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1785834

ABSTRACT

Saffron is a valued herb, obtained from the stigmas of the C. sativus Linn (Iridaceae), with therapeutic effects. It has been described in pharmacopoeias to be variously acting, including as an anti-depressant, anti-carcinogen, and stimulant agent. The therapeutic effects of saffron are harbored in its bioactive molecules, notably crocins, the subject of this paper. Crocins have been demonstrated to act as a monoamine oxidase type A and B inhibitor. Furthermore, saffron petal extracts have experimentally been shown to impact contractile response in electrical field stimulation. Other research suggests that saffron also inhibits the reuptake of monoamines, exhibits N-methyl-d-aspartate antagonism, and improves brain-derived neurotrophic factor signaling. A host of experimental studies found saffron/crocin to be similarly effective as fluoxetine and imipramine in the treatment of depression disorders. Saffron and crocins propose a natural solution to combat depressive disorders. However, some hurdles, such as stability and delivery, need to be overcome.


Subject(s)
Biological Products , Crocus , Carotenoids/pharmacology , Coloring Agents , Plant Extracts/pharmacology
11.
Mar Drugs ; 20(3)2022 Mar 20.
Article in English | MEDLINE | ID: covidwho-1760762

ABSTRACT

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of -8.8, -8.6, -9.8, -11.4, -8.0, -11.4, and -9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential.


Subject(s)
Antifungal Agents , Biological Products , COVID-19/drug therapy , Mucormycosis/drug therapy , Porifera/chemistry , SARS-CoV-2 , Animals , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacokinetics , Antifungal Agents/toxicity , Biological Products/chemistry , Biological Products/isolation & purification , Biological Products/pharmacokinetics , Biological Products/toxicity , COVID-19/complications , Coinfection , Fungal Proteins/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Mucormycosis/etiology , Toxicity Tests, Acute
12.
Phytomedicine ; 100: 154080, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1757739

ABSTRACT

BACKGROUND: Names of natural products (NP) are usually given depending on the species of origin, be it a plant, a marine organism or a microbial species. In some cases, names have been given with reference to people, animals, music, foods or places. Many NP refer to countries, cities or specific places such as mountains, deserts, seas and oceans. PURPOSE: On the basis of NP names, a world tour has been imagined referring to more than one hundred NP with names evocative of over 50 countries and regions. RESULTS: The world tour goes from UK (britannin) to Italy (vaticanol) in Europe, from Uganda (ugandoside) to Senegal (senegalene, senegalenines) in Africa, from Brazil (brasilin) to Chile (santiaguine) in South America, from Utah (utahin) to Florida (floridanolide) in the US. It includes Central America (mexicanin, panamine) and the Caribbean islands (jamaicin, bahamaolides). It also crosses Alaska (alaskene) and Canada (quebecol, canadaline). The tour continues throughout Asia, from Thailand (thailandine) to China (Chinaldine) and Pakistan (pakistanamine), to finally reaches Oceania with Australia (australigenin) and Vanuatu (vanuatine), among other countries. This virtual journey, without bordure or wall, brings us to the highest mountains (himalayamine), the deepest oceans (pacificins) and the largest deserts (desertomycin). CONCLUSION: In the current period of COVID-19 pandemia, with restricted opportunities for international travels, this NP name-based virtual journey offers a world tour to learn more from nature and to inspire scientists to contribute to the field of NP discovery and drug design. There are also limitations associated with the use of trivial names for NP. NP names can be further exploited for teaching and learning.


Subject(s)
Biological Products , COVID-19 , Animals , Brazil , COVID-19/epidemiology , Europe , Humans , Thailand
13.
Sci Rep ; 11(1): 22796, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1758351

ABSTRACT

The current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.


Subject(s)
Antiviral Agents/analysis , Drug Evaluation, Preclinical/methods , SARS-CoV-2/drug effects , Biological Products/analysis , Biological Products/pharmacology , COVID-19/drug therapy , COVID-19/metabolism , Computational Biology/methods , Coronavirus 3C Proteases/drug effects , Coronavirus 3C Proteases/metabolism , Drug Discovery/methods , Flavonols/metabolism , Flavonols/pharmacology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
14.
J Biol Chem ; 297(6): 101362, 2021 12.
Article in English | MEDLINE | ID: covidwho-1751075

ABSTRACT

The Nsp9 replicase is a conserved coronaviral protein that acts as an essential accessory component of the multi-subunit viral replication/transcription complex. Nsp9 is the predominant substrate for the essential nucleotidylation activity of Nsp12. Compounds specifically interfering with this viral activity would facilitate its study. Using a native mass-spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin, capable of binding to purified SARS-CoV-2 Nsp9 with micromolar affinities. By determining the crystal structure of the Nsp9-oridonin complex, we showed that oridonin binds through a conserved site near Nsp9's C-terminal GxxxG-helix. In enzymatic assays, oridonin's binding to Nsp9 reduces its potential to act as substrate for Nsp12's Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain. We also showed using in vitro cellular assays oridonin, while cytotoxic at higher doses has broad antiviral activity, reducing viral titer following infection with either SARS-CoV-2 or, to a lesser extent, MERS-CoV. Accordingly, these preliminary findings suggest that the oridonin molecular scaffold may have the potential to be developed into an antiviral compound to inhibit the function of Nsp9 during coronaviral replication.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Diterpenes, Kaurane/pharmacology , RNA-Binding Proteins/metabolism , SARS-CoV-2/drug effects , Viral Nonstructural Proteins/metabolism , Virus Replication/drug effects , Animals , Antiviral Agents/chemistry , Binding Sites/drug effects , Biological Products/chemistry , Biological Products/pharmacology , COVID-19/metabolism , COVID-19/virology , Chlorocebus aethiops , Diterpenes, Kaurane/chemistry , Humans , Molecular Docking Simulation , RNA-Binding Proteins/chemistry , SARS-CoV-2/chemistry , SARS-CoV-2/physiology , Vero Cells , Viral Nonstructural Proteins/chemistry
15.
J Nat Prod ; 85(3): 657-665, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1740392

ABSTRACT

Since early 2020, disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, causing millions of infections and deaths worldwide. Despite rapid deployment of effective vaccines, it is apparent that the global community lacks multipronged interventions to combat viral infection and disease. A major limitation is the paucity of antiviral drug options representing diverse molecular scaffolds and mechanisms of action. Here we report the antiviral activities of three distinct marine natural products─homofascaplysin A (1), (+)-aureol (2), and bromophycolide A (3)─evidenced by their ability to inhibit SARS-CoV-2 replication at concentrations that are nontoxic toward human airway epithelial cells. These compounds stand as promising candidates for further exploration toward the discovery of novel drug leads against SARS-CoV-2.


Subject(s)
Biological Products , COVID-19 , Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Epithelial Cells , Humans , SARS-CoV-2
16.
Molecules ; 27(5)2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1732132

ABSTRACT

The COVID-19 pandemic has led to the search for new molecules with antiviral activity against SARS-CoV-2. The entry of the virus into the cell is one of the main targets for inhibiting SARS-CoV-2 infection. Natural products are an important source of new therapeutic alternatives against diseases. Pseudotyped viruses allow the study of SARS-CoV-2 viral entry inhibitors, and due to their simplicity, they allow the screening of a large number of antiviral candidates in Biosafety Level 2 facilities. We used pseudotyped HIV-1 with the D614G SARS-CoV-2 spike glycoprotein to test its ability to infect ACE2-expressing HEK 293T cells in the presence of diverse natural products, including 21 plant extracts, 7 essential oils, and 13 compounds from plants and fungi. The 50% cytotoxic concentration (CC50) was evaluated using the resazurin method. From these analyses, we determined the inhibitory activity of the extract of Stachytarpheta cayennensis, which had a half-maximal inhibitory concentration (IC50) of 91.65 µg/mL, a CC50 of 693.5 µg/mL, and a selectivity index (SI) of 7.57, indicating its potential use as an inhibitor of SARS-CoV-2 entry. Moreover, our work indicates the usefulness of the pseudotyped-virus system in the screening of SARS-CoV-2 entry inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/chemistry , Virus Internalization/drug effects , Actinobacteria/chemistry , Actinobacteria/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Biological Products/metabolism , Biological Products/pharmacology , Biological Products/therapeutic use , COVID-19/drug therapy , COVID-19/virology , HEK293 Cells , High-Throughput Screening Assays/methods , Humans , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Plant Extracts/chemistry , Plant Extracts/metabolism , Plant Extracts/pharmacology , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism
17.
Molecules ; 27(5)2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1732131

ABSTRACT

The angiotensin-converting enzyme II (ACE2) is a multifunctional protein in both health and disease conditions, which serves as a counterregulatory component of RAS function in a cardioprotective role. ACE2 modulation may also have relevance to ovarian cancer, diabetes, acute lung injury, fibrotic diseases, etc. Furthermore, since the outbreak of the coronavirus disease in 2019 (COVID-19), ACE2 has been recognized as the host receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The receptor binding domain of the SARS-CoV-2 S-protein has a strong interaction with ACE2, so ACE2 may be a potent drug target to prevent the virus from invading host cells for anti-COVID-19 drug discovery. In this study, structure- and property-based virtual screening methods were combined to filter natural product databases from ChemDiv, TargetMol, and InterBioScreen to find potential ACE2 inhibitors. The binding affinity between protein and ligands was predicted using both Glide SP and XP scoring functions and the MM-GBSA method. ADME properties were also calculated to evaluate chemical drug-likeness. Then, molecular dynamics (MD) simulations were performed to further explore the binding modes between the highest-potential compounds and ACE2. Results showed that the compounds 154-23-4 and STOCK1N-07141 possess potential ACE2 inhibition activities and deserve further study.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Biological Products/chemistry , Protease Inhibitors/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , Biological Products/metabolism , Biological Products/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Databases, Chemical , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/metabolism , Protease Inhibitors/therapeutic use , Protein Binding , SARS-CoV-2/isolation & purification , Structure-Activity Relationship , Thermodynamics
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(2): 216-222, 2022 Feb 15.
Article in English, Chinese | MEDLINE | ID: covidwho-1716083

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a type of hyperinflammatory symptoms similar to Kawasaki disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is commonly observed in children aged 8-10 years. Primary therapeutic medications for MIS-C are intravenous immunoglobulins and glucocorticoids. It has been reported that biologics, such as IL-1 receptor antagonist anakinra, IL-6 receptor antagonist tocilizumab, and TNF-α receptor antagonist infliximab, can be used as an option for critically ill patients. This article elaborates on the mechanism of action of the above biologics and discusses the efficacy and safety biologics in the treatment of MIS-C after SARS-CoV-2 infection, in order to provide methods for the treatment of MIS-C with severe symptoms.


Subject(s)
Biological Products , COVID-19 , COVID-19/complications , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
19.
Molecules ; 27(4)2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1715567

ABSTRACT

Alkaloids are nitrogen-containing compounds, biosynthesized by both marine and terrestrial organisms, often with strong biological properties [...].


Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Drug Discovery , Alkaloids/isolation & purification , Aquatic Organisms/chemistry , Biological Products , Drug Discovery/methods , Plant Extracts
20.
Dermatol Ther ; 35(5): e15408, 2022 May.
Article in English | MEDLINE | ID: covidwho-1714163

ABSTRACT

It is unclear whether biological antipsoriatic therapies affect seroconversion after messenger ribonucleic acid (mRNA)-based antisevere acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) vaccinations. To assess antibody formation and the incidence of side effects after anti-SARS-CoV-2 mRNA vaccinations in psoriatic patients receiving different biologicals compared to healthy controls. 102 moderate-to-severe psoriatic patients (56.2 [±13.5] years) and 55 age-matched healthy (56.4 ± 13.6 years) volunteers were included in our study. Ten to 21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccine, antibody levels specific to the SARS-CoV-2 spike (S) protein receptor binding domain were monitored. The incidence of postvaccination side effects was recorded and compared to real-life data in the literature. Of the 102 patients, 57 (55.88%) received tumor necrosis factor (TNF), 28 (27.45%) received interleukin (IL)-12/23, 16 (15.68%) received IL-17, and 1 (0.99%) received IL-23 inhibitors. No significant differences in the median serum level of anti-SARS-CoV-2S antibody were observed between the study population and the control group (median IQR range: 1681.0 U/mL (600.0-4844.0) versus 1984.0 U/mL (1000.0-3136.0; p = 0.82). The most frequent side effects of the mRNA vaccines within 7 days after the administration of both dosages were arm pain on the side of injection (23.53% and 23.53%), fatigue (9.80% and 13.72%), headache (4.9% and 5.88%), and chills or shivering (4.9% and 8.82%). Detectable antibodies against SARS-CoV-2S protein appear 10-21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccines in moderate-to-severe psoriatic patients receiving biologicals, similar to those of healthy controls.


Subject(s)
Biological Products , COVID-19 , Adult , Aged , Biological Products/adverse effects , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Middle Aged , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Seroconversion , Vaccination/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL