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1.
Mar Drugs ; 20(3)2022 Feb 24.
Article in English | MEDLINE | ID: covidwho-1725847

ABSTRACT

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 Mpro with IC50 value of 0.47 µM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 Mpro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related Mpro inhibitors.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Cysteine Proteinase Inhibitors/chemistry , Indole Alkaloids/chemistry , Piperazines/chemistry , SARS-CoV-2/enzymology , Alkaloids/chemistry , Alkaloids/isolation & purification , Antiviral Agents/isolation & purification , Aspergillus fumigatus/chemistry , Cysteine Proteinase Inhibitors/isolation & purification , Indole Alkaloids/isolation & purification , Molecular Docking Simulation , Molecular Dynamics Simulation , Piperazines/isolation & purification
2.
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
3.
Chem Biodivers ; 19(1): e202100668, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1611203

ABSTRACT

Forsyqinlingines C (1) and D (2), two C9 -monoterpenoid alkaloids bearing a rare skeleton, were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute configurations, were fully elucidated by extensive spectroscopic data and ECD experiments. The plausible biogenetic pathway for compounds 1 and 2 was also proposed. In vitro, two C9 -monoterpenoid alkaloids showed anti-inflammatory activity performed by the inhibitory effect on the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), as well as antiviral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV).


Subject(s)
Alkaloids/chemistry , Anti-Inflammatory Agents/chemistry , Antiviral Agents/chemistry , Forsythia/chemistry , Monoterpenes/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Forsythia/metabolism , Fruit/chemistry , Fruit/metabolism , Glucuronidase/metabolism , Influenza A Virus, H1N1 Subtype/drug effects , Magnetic Resonance Spectroscopy , Molecular Conformation , Neutrophils/cytology , Neutrophils/drug effects , Neutrophils/metabolism , Platelet Activating Factor/pharmacology , Rats , Respiratory Syncytial Viruses/drug effects
4.
Molecules ; 26(20)2021 Oct 13.
Article in English | MEDLINE | ID: covidwho-1526851

ABSTRACT

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = -7.78, -7.65, -6.39, -6.28, -8.84 Kcal/mol) for the main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.


Subject(s)
Alkaloids/chemistry , SARS-CoV-2/metabolism , Alkaloids/isolation & purification , Alkaloids/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/virology , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Halogenation , Humans , Isoxazoles/chemistry , Isoxazoles/metabolism , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Structure-Activity Relationship , Tyrosine/analogs & derivatives , Tyrosine/chemistry , Tyrosine/metabolism
5.
Curr Pharm Biotechnol ; 22(4): 444-450, 2021.
Article in English | MEDLINE | ID: covidwho-630363

ABSTRACT

BACKGROUND: The aim of the present review is to provide basic knowledge regarding the treatment of Coronavirus via medicinal plants. Coronavirus (COVID-19, SARS-CoV, and MERS-CoV) as a viral pneumonia causative agent, has infected thousands of people in China and worldwide. Currently, there is no specific medicine or vaccine available that can treat or prevent this virus and this has posed a severe threat to human health; therefore, there is an urgent need to develop a novel drug or anticoronavirus vaccine. However, natural compounds to treat coronaviruses are the most effective alternative and complementary therapies due to their diverse range of biological and therapeutic properties. METHODS: We performed an open-ended, English restricted search of Scopus database, Web of Science, and Pubmed for all available literature from Jan-March, 2020, using terms related to phytochemical compounds, medicinal plants and coronavirus. RESULTS: The view on anti-coronavirus (anti-CoV) activity in the plant-derived phytochemicals and medicinal plants gives a strong base to develop a novel treatment employing these compounds for coronavirus. Various phytochemicals and medicinal plant extracts have been revised and are considered as potential anti-CoV agents for effective control of the virus and future drug development. Herein, we discuss some important plants (Scutellaria baicalensis, Psorothamnus arborescens, Glycyrrhiza radix, Glycyrrhiza uralensis, Lycoris radiate, Phyllanthus emblica, Camellia sinensis, Hyptis atrorubens Poit, Fraxinus sieboldiana, Erigeron breviscapus, Citri Reticulatae Pericarpium, Amaranthus tricolor, Phaseolus vulgaris, Rheum palmatum, Curcuma longa and Myrica cerifera) that have emerged to have broad-spectrum antiviral activity. CONCLUSION: Nigella sativa has potent anti-SARS-CoV activity and it might be a useful source for developing novel antiviral therapies for coronavirus.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/drug effects , Phytochemicals/therapeutic use , Plants, Medicinal , SARS-CoV-2/drug effects , /drug effects , Alkaloids/isolation & purification , Alkaloids/pharmacology , Alkaloids/therapeutic use , Animals , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/immunology , Curcuma , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Nigella sativa , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , SARS-CoV-2/immunology , Scutellaria baicalensis
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