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1.
RSC advances ; 12(30):19505-19511, 2022.
Article in English | EuropePMC | ID: covidwho-1939968

ABSTRACT

In late December 2019, a pandemic coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread all over the globe. One of the promising therapeutic techniques of viral infection is to search for enzyme inhibitors among natural phytochemicals using molecular docking to obtain leads with the least side effects. The COVID-19 virus main protease (Mpro) is considered as an attractive target due to its pivotal role in controlling viral transcription and replication. Metabolic profiling of the crude extract of Livistona decipiens Becc. (Arecaceae) leaves and fruit dereplicated twelve metabolites using LC-HRESIMS. Molecular docking simulation and in silico ADME profiling of these annotated compounds proposed that tricin is a promising lead against COVID-19 virus Mpro. The alcoholic extract was shown to inhibit SARS-CoV-2 through in vitro culture and RT-PCR testing with EC50 = 0.122 and 1.53 μg mL−1 for leaves and fruit extracts, respectively, when compared with that of the FDA-approved anti-COVID-19 remdesivir (0.002 μg mL−1). Preliminary steps were also performed including the 3CL-protease inhibition assay and cytotoxicity study. It is worthwhile to find a cheap, safe, natural source for promising anti-SARS-CoV-2 agents that can be further tested in vivo against the COVID-19 virus Mpro. This study provides scientific basis for demonstrating beneficial effects of L. decipiens application on human health during the corona pandemic. Promising natural inhibitors for COVID-19.

2.
RSC Adv ; 12(30): 19505-19511, 2022 Jun 29.
Article in English | MEDLINE | ID: covidwho-1937458

ABSTRACT

In late December 2019, a pandemic coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread all over the globe. One of the promising therapeutic techniques of viral infection is to search for enzyme inhibitors among natural phytochemicals using molecular docking to obtain leads with the least side effects. The COVID-19 virus main protease (Mpro) is considered as an attractive target due to its pivotal role in controlling viral transcription and replication. Metabolic profiling of the crude extract of Livistona decipiens Becc. (Arecaceae) leaves and fruit dereplicated twelve metabolites using LC-HRESIMS. Molecular docking simulation and in silico ADME profiling of these annotated compounds proposed that tricin is a promising lead against COVID-19 virus Mpro. The alcoholic extract was shown to inhibit SARS-CoV-2 through in vitro culture and RT-PCR testing with EC50 = 0.122 and 1.53 µg mL-1 for leaves and fruit extracts, respectively, when compared with that of the FDA-approved anti-COVID-19 remdesivir (0.002 µg mL-1). Preliminary steps were also performed including the 3CL-protease inhibition assay and cytotoxicity study. It is worthwhile to find a cheap, safe, natural source for promising anti-SARS-CoV-2 agents that can be further tested in vivo against the COVID-19 virus Mpro. This study provides scientific basis for demonstrating beneficial effects of L. decipiens application on human health during the corona pandemic.

3.
RSC advances ; 10(34):19790-19802, 2020.
Article in English | EuropePMC | ID: covidwho-1888172

ABSTRACT

The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (Mpro). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates, viz. acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future. Potential drug candidates derived from natural sources are posed for the development of anti-SARS CoV-2 therapeutics.

4.
RSC advances ; 11(28):16970-16979, 2021.
Article in English | EuropePMC | ID: covidwho-1812573

ABSTRACT

COVID-19 is a global pandemic first identified in China, causing severe acute respiratory syndrome. One of the therapeutic strategies for combating viral infections is the search for viral spike proteins as attachment inhibitors among natural compounds using molecular docking. This review aims at shedding light on the antiviral potential of natural products belonging to the natural-products class of coumarins up to 2020. Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and the best 74 compounds were selected. Using virtual-screening methods, the selected compounds were investigated for potential inhibition of viral main protease (Mpro), viral methyltransferase (nsp16/10 complex), viral recognition binding domain (RBD) of S-protein, and human angiotensin-converting enzyme 2 (ACE2), which is the human receptor for viral S-protein targets, using molecular-docking studies. Promising potential results against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented. Potential of coumarins against Covid-19.

5.
Mar Drugs ; 20(3)2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1715534

ABSTRACT

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.


Subject(s)
Antiviral Agents/pharmacology , Chromones/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , Animals , Antiviral Agents/isolation & purification , Aspergillus niger/chemistry , Chlorocebus aethiops , Chromones/isolation & purification , Coronavirus 3C Proteases/metabolism , Coronavirus Papain-Like Proteases/metabolism , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Molecular Docking Simulation , Protease Inhibitors/isolation & purification , RNA Helicases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
6.
Metabolites ; 11(12)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542668

ABSTRACT

Coronavirus disease 2019 (COVID-19) is the disease caused by the virus SARS-CoV-2 responsible for the ongoing pandemic which has claimed the lives of millions of people. This has prompted the scientific research community to act to find treatments against the SARS-CoV-2 virus that include safe antiviral medicinal compounds. The edible green algae U. lactuca. is known to exhibit diverse biological activities such as anti-influenza virus, anti-Japanese encephalitis virus, immunomodulatory, anticoagulant, antioxidant and antibacterial activities. Herein, four new ceramides in addition to two known ones were isolated from Ulva lactuca. The isolated ceramides, including Cer-1, Cer-2, Cer-3, Cer-4, Cer-5 and Cer-6 showed promising antiviral activity against SARS-CoV-2 when investigated using in silico approaches by preventing its attachment to human cells and/or inhibiting its viral replication. Cer-4 and Cer-5 were the most effective in inhibiting the human angiotensin converting enzyme (hACE)-spike protein complex which is essential for the virus to enter the human host. In addition to this, Cer-4 also showed an inhibition of the SARS-CoV-2 protease (Mpro) that is responsible for its viral replication and transcription. In this study, we also used liquid chromatography coupled to electrospray ionization high-resolution mass spectroscopy (LC-ESI-HRMS) to identify several metabolites of U. lactuca, including metabolites such as fatty acids, their glyceride derivatives, terpenoids, sterols and oxysterols from the organic extract. Some of these metabolites also possessed promising antiviral activity, as previously reported.

7.
RSC Adv ; 11(57): 36042-36059, 2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1537345

ABSTRACT

Cerebrosides are a group of metabolites belonging to the glycosphingolipids class of natural products. So far, 167 cerebrosides, compounds 1-167, have been isolated from diverse marine organisms or microorganisms. The as yet smaller number of compounds that have been studied more in depth proves a potential against challenging diseases, such as cancer, a range of viral and bacterial diseases, as well as inflammation. This review provides a comprehensive summary on this so far under-explored class of compounds, their chemical structures, bioactivities, and their marine sources, with a full coverage to the end of 2020. Today, the global pandemic concern, COVID-19, has claimed millions of death cases around the world, making the development of anti-SARS-CoV-2 drugs urgently needed for such a battle. Accordingly, selected examples from all subclasses of cerebrosides were virtually screened for potential inhibition of SARS-CoV-2 proteins that are crucially involved in the viral-host interaction, viral replication, or in disease progression. The results highlight five cerebrosides that could preferentially bind to the hACE2 protein, with binding scores between -7.1 and -7.6 kcal mol-1 and with the docking poses determined underneath the first α1-helix of the protein. Moreover, the molecular interaction determined by molecular dynamic (MD) simulation revealed that renieroside C1 (60) is more conveniently involved in key hydrophobic interactions with the best stability, least deviation, least ΔG (-6.9 kcal mol-1) and an RMSD value of 3.6 Å. Thus, the structural insights assure better binding affinity and favorable molecular interaction of renieroside C1 (60) towards the hACE2 protein, which plays a crucial role in the biology and pathogenesis of SARS-CoV-2.

8.
Antibiotics (Basel) ; 10(7)2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1302137

ABSTRACT

SARS-CoV-2 (COVID-19), a novel coronavirus causing life-threatening pneumonia, caused a pandemic starting in 2019 and caused unprecedented economic and health crises all over the globe. This requires the rapid discovery of anti-SARS-CoV-2 drug candidates to overcome this life-threatening pandemic. Strawberry (Fragaria ananassa Duch.) and ginger (Zingiber officinale) methanolic extracts were used for silver nanoparticle (AgNPs) synthesis to explore their SARS-CoV-2 inhibitory potential. Moreover, an in silico study was performed to explore the possible chemical compounds that might be responsible for the anti-SARS-CoV-2 potential. The characterization of the green synthesized AgNPs was carried out with transmission electron microscope (TEM), Fourier-transform infrared, spectroscopy ultraviolet-visible spectroscopy, zeta potential, and a dynamic light-scattering technique. The metabolic profiling of strawberry and ginger methanolic extract was assessed using liquid chromatography coupled with high-resolution mass spectrometry. The antiviral potential against SARS-CoV-2 was evaluated using an MTT assay. Moreover, in silico modeling and the molecular dynamic study were conducted via AutoDock Vina to demonstrate the potential of the dereplicated compounds to bind to some of the SARS-CoV-2 proteins. The TEM analysis of strawberry and ginger AgNPs showed spherical nanoparticles with mean sizes of 5.89 nm and 5.77 nm for strawberry and ginger, respectively. The UV-Visible spectrophotometric analysis showed an absorption peak at λmax of 400 nm for strawberry AgNPs and 405 nm for ginger AgNPs. The Zeta potential values of the AgNPs of the methanolic extract of strawberry was -39.4 mV, while for AgNPs of ginger methanolic extract it was -42.6 mV, which indicates a high stability of the biosynthesized nanoparticles. The strawberry methanolic extract and the green synthesized AgNPs of ginger showed the highest antiviral activity against SARS-CoV-2. Dereplication of the secondary metabolites from the crude methanolic extracts of strawberry and ginger resulted in the annotation of different classes of compounds including phenolic, flavonoids, fatty acids, sesquiterpenes, triterpenes, sterols, and others. The docking study was able to predict the different patterns of interaction between the different compounds of strawberry and ginger with seven SARS-CoV-2 protein targets including five viral proteins (Mpro, ADP ribose phosphatase, NSP14, NSP16, PLpro) and two humans (AAK1, Cathepsin L). The molecular docking and dynamics simulation study showed that neohesperidin demonstrated the potential to bind to both human AAK1 protein and SARS-CoV-2 NSP16 protein, which makes this compound of special interest as a potential dual inhibitor. Overall, the present study provides promise for Anti-SARS-CoV-2 green synthesized AgNPs, which could be developed in the future into a new anti-SARS-CoV-2 drug.

9.
Molecules ; 26(12)2021 Jun 21.
Article in English | MEDLINE | ID: covidwho-1282543

ABSTRACT

Since December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and serious health problems worldwide. In this study, we investigated 14 natural compounds isolated from Amphimedon sp. via a molecular docking study, to examine their ability to act as anti-COVID-19 agents. Moreover, the pharmacokinetic properties of the most promising compounds were studied. The docking study showed that virtually screened compounds were effective against the new coronavirus via dual inhibition of SARS-CoV-2 RdRp and the 3CL main protease. In particular, nakinadine B (1), 20-hepacosenoic acid (11) and amphimedoside C (12) were the most promising compounds, as they demonstrated good interactions with the pockets of both enzymes. Based on the analysis of the molecular docking results, compounds 1 and 12 were selected for molecular dynamics simulation studies. Our results showed Amphimedon sp. to be a rich source for anti-COVID-19 metabolites.


Subject(s)
Biological Products/chemistry , Biological Products/pharmacology , Coronavirus 3C Proteases/chemistry , Porifera/chemistry , Porifera/metabolism , RNA-Dependent RNA Polymerase/chemistry , SARS-CoV-2/drug effects , Amino Sugars/chemistry , Amino Sugars/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Binding Sites , Biological Products/isolation & purification , Biological Products/pharmacokinetics , COVID-19/drug therapy , Computational Biology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Humans , Ligands , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Pyridines/chemistry , Pyridines/pharmacology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/enzymology , SARS-CoV-2/metabolism
10.
RSC Adv ; 11(28): 16970-16979, 2021 May 06.
Article in English | MEDLINE | ID: covidwho-1246407

ABSTRACT

COVID-19 is a global pandemic first identified in China, causing severe acute respiratory syndrome. One of the therapeutic strategies for combating viral infections is the search for viral spike proteins as attachment inhibitors among natural compounds using molecular docking. This review aims at shedding light on the antiviral potential of natural products belonging to the natural-products class of coumarins up to 2020. Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and the best 74 compounds were selected. Using virtual-screening methods, the selected compounds were investigated for potential inhibition of viral main protease (Mpro), viral methyltransferase (nsp16/10 complex), viral recognition binding domain (RBD) of S-protein, and human angiotensin-converting enzyme 2 (ACE2), which is the human receptor for viral S-protein targets, using molecular-docking studies. Promising potential results against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.

11.
Nat Prod Res ; : 1-4, 2021 May 23.
Article in English | MEDLINE | ID: covidwho-1240854

ABSTRACT

The ongoing spread of SARS-CoV-2 has created a growing need to develop effective antiviral treatments; therefore, this work was undertaken to delve into the natural metabolites of the Red Sea soft coral Nephthea sp. (family Nephtheidae) as a source of potential anti-COVID-19 agents. Overall, a total of 14 structurally diverse minor constituents were isolated and identified from the petroleum ether fraction of Nephthea sp. The characterised compounds were screened and compared for their inhibitory potential against SARS-CoV-2 main protease (Mpro) using Autodock Vina and MOE software. Interestingly, most compounds were able to bind effectively to the active site of Mpro, of which nephthoside monoacetate (1); an acylated tetraprenyltoluquinol glycoside, exhibited the highest binding capacity in both software with comparable interaction energies to the ligand N3 and moderately acceptable drug-likeness properties, which drew attention to the relevance of marine-derived metabolites from Nephthea sp., particularly compound (1), to develop potential SARS-CoV-2 protease inhibitors.

12.
Antibiotics (Basel) ; 10(5)2021 May 07.
Article in English | MEDLINE | ID: covidwho-1223913

ABSTRACT

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract's antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein-protein and protein-compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

13.
Nat Prod Res ; : 1-5, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1216555

ABSTRACT

One of the promising therapeutic strategies for corona virus 2019 (COVID-19) is tolook for enzyme inhibitors. COVID-19 virus main protease (Mpro) plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target. LC-ESI-HDMS based metabolic profiling of Citrus nobilis Lour. × Citrus deliciosa Ten. (Rutaceae) annotated 21 compounds belonging to diverse classes. Molecular docking studies were carried out to ascertain the inhibitory action of studied dereplicated compounds through the interactions within the active site of SARS-CoV-2 (Mpro). Among which, quercetin-7-O-glucoside-3-O-rutinoside (21) possessed the best binding affinity (-9.47 kcal/mol), followed by luteoline-7-rutinoside (18), quercetin-3-O-rutinoside (19) and apigenin-8-C-glucoside (15) showed less binding affinities ranging at -8.27, -7.97 and -6.94 kcal/mol respectively.

14.
Antibiotics (Basel) ; 10(4)2021 Apr 11.
Article in English | MEDLINE | ID: covidwho-1178064

ABSTRACT

SARS CoV-2 is still considered a global health issue, and its threat keeps growing with the emergence of newly evolved strains. Despite the success in developing some vaccines as a protective measure, finding cost-effective treatments is urgent. Accordingly, we screened a number of phenolic natural compounds for their in vitro anti-SARS CoV-2 activity. We found sinapic acid (SA) selectively inhibited the viral replication in vitro with an half-maximal inhibitory concentration (IC50) value of 2.69 µg/mL with significantly low cytotoxicity (CC50 = 189.3 µg/mL). Subsequently, we virtually screened all currently available molecular targets using a multistep in silico protocol to find out the most probable molecular target that mediates this compound's antiviral activity. As a result, the viral envelope protein (E-protein) was suggested as the most possible hit for SA. Further in-depth molecular dynamic simulation-based investigation revealed the essential structural features of SA antiviral activity and its binding mode with E-protein. The structural and experimental results presented in this study strongly recommend SA as a promising structural motif for anti-SARS CoV-2 agent development.

15.
RSC Adv ; 10(53): 32148-32155, 2020 Aug 26.
Article in English | MEDLINE | ID: covidwho-1177116

ABSTRACT

SARS-CoV-2 is a novel coronavirus that was first identified during the outbreak in Wuhan, China in 2019. It is an acute respiratory illness that can transfer among human beings. Natural products can provide a rich resource for novel antiviral drugs. They can interfere with viral proteins such as viral proteases, polymerases, and entry proteins. Several naturally occurring flavonoids were reported to have antiviral activity against different types of RNA and DNA viruses. A methanolic extract of Manilkara hexandra (Roxb.) Dubard leaves is rich in phenolic compounds, mainly flavonoids. Metabolic profiling of the secondary metabolites of Manilkara hexandra (Roxb.) Dubard leaves methanolic extract (MLME), and bark ethyl acetate (MBEE) extract using LC-HRESIMS resulted in the isolation of 18 compounds belonging to a variety of constituents, among which phenolic compounds, flavones, flavonol glycosides and triterpenes were predominant. Besides, four compounds (I-IV) were isolated and identified as myricetin I, myricitrin II, mearnsitrin III, and mearnsetin-3-O-ß-d-rutinoside IV (compound IV is isolated for the first time from genus Manilkara) and dereplicated in a metabolomic study as compounds 3, 5, 6, and 12, respectively. The molecular docking study showed that rutin, myricitrin, mearnsitrin, and quercetin 3-O-ß-d-glucoside have strong interaction with SARS-CoV-2 protease with high binding energy of -8.2072, -7.1973, -7.5855, and -7.6750, respectively. Interestingly, the results proved that rutin which is a citrus flavonoid glycoside exhibits the strongest inhibition effect to the SARS-CoV-2 protease enzyme. Consequently, it can contribute to developing an effective antiviral drug lead against the SARS-CoV-2 pandemic.

16.
J Biomol Struct Dyn ; : 1-13, 2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1087592

ABSTRACT

The COVID-19 pandemic in Egypt is a part of the worldwide global crisis of coronavirus 2 (SARS-CoV-2). The contagious life-threatening condition causes acute respiratory syndrome. The present study aimed to assess the compounds identified by LC-MS of the methanolic leaves extracts from three conifers trees cultivated in Egypt (Araucaria bidwillii, Araucaria. cunninghamii and Araucaria heterophylla) via docking technique as potential inhibitor of COVID-19 virus on multiple targets; viral main protease (Mpro, 6LU7), non-structural protein-16 which is a methyl transferase (nsp16, 6W4H) and RNA dependent RNA polymerase (nsp12, 7BV2). Among the three targets, nsp16 was the best target recognized by the tested compounds as can be deduced from docking studies. Moreover, the methanolic extract of A. cunninghamii showed the highest radical-scavenging activity using (DPPH test) with 53.7 µg/mL comparable to ascorbic acid with IC50 = 46 µg/mL The anti-inflammatory potential carried using enzyme linked immunoassay showed the highest activity for A. cunninghamii and A. bidwillii followed by A. heterophylla with IC50 = 23.20 ± 1.17 µg/mL, 82.83 ± 3.21 µg/mL and 221.13 ± 6.7 µg/mL, respectively (Celecoxib was used as a standard drug with IC50 = 141.92 ± 4.52 µg/mL). Moreover, a molecular docking study was carried for the LC-MS annotated metabolites to validate their anti-inflammatory inhibitory effect using Celecoxib as a reference compound and showed a high docking score (-7.7 kcal/mol) for Octadecyl (E) P-coumarate and (-7.3 kcal/mol) for secoisolariciresinol rhamnoside.Communicated by Ramaswamy H. Sarma.

17.
J Biomol Struct Dyn ; : 1-11, 2020 Dec 15.
Article in English | MEDLINE | ID: covidwho-1024028

ABSTRACT

The novel strain of human coronavirus, emerged in December 2019, which has been designated as SARS-CoV-2, causes a severe acute respiratory syndrome. Since then, it has arisen as a serious threat to the world public health. Since no approved vaccines or drugs has been found to efficiently stop the virulent spread of the virus, progressive inquiries targeting these viruses are urgently needed, especially those from plant sources. Metabolic profiling using LC-HR-ESI-MS of the butanol extract of Ocimum menthiifolium (Lamiaceae) aerial parts yielded 10 compounds including flavonoids, iridoids and phenolics. As it has been previously reported that some flavonoids can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose to examine 14 flavonoids (detected by metabolomics and other compounds isolated via several chromatographic techniques). We investigated their potential binding interactions with the 4 main SARS-CoV-2 targets: Mpro, nsp16/nsp10 complex, ACE2-PD and RBD-S-protein via molecular docking. Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol. Furthermore, the stability of these complexes was studied using molecular dynamics of 150 ns, which were then compared to their complexes in the other three targets. MM-PBSA calculations suggested the high stability of acaciin-nsp16 complex with binding energy of -110 kJ/mol. This study sheds light on the structure-based design of natural flavonoids as anti-SARS-CoV-2 drugs targeting the nsp16/10 complex.Communicated by Ramaswamy H. Sarma.

18.
Plants (Basel) ; 10(1)2020 Dec 26.
Article in English | MEDLINE | ID: covidwho-1016217

ABSTRACT

The acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) caused severe panic all over the world. The coronavirus (COVID-19) outbreak has already brought massive human suffering and major economic disruption and unfortunately, there is no specific treatment for COVID-19 so far. Herbal medicines and purified natural products can provide a rich resource for novel antiviral drugs. Therefore, in this review, we focused on the sterols and triterpenes as potential candidates derived from natural sources with well-reported in vitro efficacy against numerous types of viruses. Moreover, we compiled from these reviewed compounds a library of 162 sterols and triterpenes that was subjected to a computer-aided virtual screening against the active sites of the recently reported SARS-CoV-2 protein targets. Interestingly, the results suggested some compounds as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics.

19.
Plants ; 10(1):41, 2021.
Article in English | ScienceDirect | ID: covidwho-984379

ABSTRACT

The acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) caused severe panic all over the world. The coronavirus (COVID-19) outbreak has already brought massive human suffering and major economic disruption and unfortunately, there is no specific treatment for COVID-19 so far. Herbal medicines and purified natural products can provide a rich resource for novel antiviral drugs. Therefore, in this review, we focused on the sterols and triterpenes as potential candidates derived from natural sources with well-reported in vitro efficacy against numerous types of viruses. Moreover, we compiled from these reviewed compounds a library of 162 sterols and triterpenes that was subjected to a computer-aided virtual screening against the active sites of the recently reported SARS-CoV-2 protein targets. Interestingly, the results suggested some compounds as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics.

20.
RSC Adv ; 10(70): 43103-43108, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-989975

ABSTRACT

Coronavirus (CoV) is a positive RNA genome virus causing a global panic nowadays. Tecoma is a medicinally-valuable genus in the Bignoniaceae family, with some of its species exhibiting anti-HIV activity. This encouraged us to conduct an in silico exploration of some phytocompounds in Tecoma species cultivated in Egypt, namely Tecoma capensis and its four varieties i.e. yellow, harmony, pink and red, T. grandiflora Loisel., T. radicans L., and one hybrid i.e. Tecoma × smithii W. Watson. LC/MS-based metabolite profiling of the studied Tecoma plants resulted in the dereplication of 12 compounds (1-12) belonging to different phytochemical classes viz. alkaloids, iridoids, flavonoids and fatty acid esters. The in silico inhibitory action of these compounds against SARS-CoV-2 spike protein C-terminal domain in complex with human ACE2 was assessed via molecular docking. Succinic acid decyl-3-oxobut-2-yl ester (10), a fatty acid ester, possessed the best binding affinity (-6.77 kcal mol-1), as compared to hesperidin (13) (-7.10 kcal mol-1).

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