Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 72
Filter
1.
Curr Pharm Des ; 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1963212

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID­19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is associated with a high level of mortality. OBJECTIVE: This updated review aims to present the most important traditional medicinal plants and some of their secondary metabolites that have previously and more recently been shown to affect viruses and may represent a beneficial contributory step against SARS-CoV-2 as the cause of COVID-19. Moreover, the mechanism aspects of these secondary metabolites were discussed, which may help find more reliable drugs against SARS-CoV-2. METHODS: Articles were searched in scientific websites including Google Scholar, Scopus, Web of Science, PubMed, and IranMedex using the search terms herbal medicine and traditional medicine with coronavirus, SARS-CoV-2, or COVID-19. Human, animal, and in vitro studies were identified in the search. RESULTS: Medicinal plants and their secondary metabolites may possess a potential role in combating this disease, and researchers suggest that some of these plants and their constituent compounds have inhibitory activity on coronaviruses. Numerous medicinal plants, their extracts, and secondary metabolites have been investigated over a period of time for antiviral activity. Among them, kaempferol, silybin, myricitrin, licoleafol, and curcumin are promising agents with potential activity against SARS-CoV-2. Natural compounds can form strong bonds with the active sites of SARS-CoV-2 protease. Structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro are inhibited by these phytochemicals. CONCLUSION: Prospective treatments targeted at the life cycle stages of the virus may eventuate from research endeavors, and it must not be discounted that therapy originally derived from plant secondary metabolite sources may potentially have a part to play.

2.
Molecules ; 27(13)2022 Jun 26.
Article in English | MEDLINE | ID: covidwho-1934173

ABSTRACT

The purpose of this study was to find the biological propensities of the vegetable plant Pleurospermum candollei by investigating its phytochemical profile and biological activities. Phytochemical analysis was done by spectroscopic methods to investigate the amount of total polyphenols, and biological evaluation was done by the different antioxidant, enzyme inhibitory (tyrosinase, α-amylase, and α-glucosidase), thrombolytic, and antibacterial activities. The highest amount of total phenolic and flavonoid contents was observed in methanolic extract (240.69 ± 2.94 mg GAE/g and 167.59 ± 3.47 mg QE/g); the fractions showed comparatively less quantity (57.02 ± 1.31 to 144.02 ± 2.11 mg GAE/g, and 48.21 ± 0.75 to 96.58 ± 2.30 mg QE/g). The effect of these bioactive contents was also related to biological activities. GCMS analysis led to the identification of bioactive compounds with different biological effects from methanolic extract (antioxidant; 55.07%, antimicrobial; 56.41%), while the identified compounds from the n-hexane fraction with antioxidant properties constituted 67.86%, and those with antimicrobial effects constituted 82.95%; however, the synergetic effect of polyphenols may also have contributed to the highest value of biological activities of methanolic extract. Molecular docking was also performed to understand the relationship of identified secondary metabolites with enzyme-inhibitory activities. The thrombolytic activity was also significant (40.18 ± 1.80 to 57.15 ± 1.10 % clot lysis) in comparison with streptokinase (78.5 ± 1.53 to 82.34 ± 1.25% clot lysis). Methanolic extract also showed good activity against Gram-positive strains of bacteria, and the highest activity was observed against Bacillus subtilis. The findings of this study will improve our knowledge of phytochemistry, and biological activities of P. candollei, which seems to be a ray of hope to design formulations of natural products for the improvement of health and prevention of chronic diseases; however, further research may address the development of novel drugs for use in pharmaceuticals.


Subject(s)
Anti-Infective Agents , Apiaceae , Biological Products , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Biological Products/pharmacology , Methanol/chemistry , Molecular Docking Simulation , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyphenols/pharmacology
3.
Food Science and Human Wellness ; 11(5):1134-1142, 2022.
Article in English | Web of Science | ID: covidwho-1926460

ABSTRACT

Coronavirus pandemic infection is the most important health issue worldwide. Coronavirus disease 2019 is a contagious disease characterized by severe acute respiratory syndrome coronavirus 2. To date, excluding the possibility of vaccination, against SARS-CoV-2 infection it is possible to act only with supportive care and non-virus-specific treatments in order to improve the patient's symptoms. Pharmaceutical industry is investigating effects of medicinal plants, phytochemical extracts and aromatic herbs to find out natural substances which may act as antiviral drugs. Several studies have revealed how these substances may interfere with the viral life cycle, viral entry, replication, assembly or discharge, as well as virus-specific host targets or stimulating the host immune system, reducing oxidative stress and inflammatory response. A natural compound can be used as a prophylaxis by people professionally exposed to the risk of contagion and/or positive patients not in intensive care. The aim of this paper is to perform a narrative review of current literature in order to summarize the most studied natural compounds and their modes of action. (c) 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

4.
Ann Med Surg (Lond) ; 80: 104062, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1914134

ABSTRACT

Despite the fact that various therapeutic compounds are being investigated, there is still a scarcity of effective and reliable therapeutic regimens to treat COVID-19. Ever since the COVID-19 pandemic, a diversity of traditional herbal treatments has been investigated to cure infected people, either alone or in conjunction with mainstream pharmaceuticals, with encouraging outcomes. In this article, we look at the latest research on the usage of natural products to alleviate the severity of COVID-19. To determine the activity of the natural products, act against SARS-CoV-2 to various targets like Mpro, ACE-II, papain-like, chymotrypsin-like proteases, and some antiviral targets. The processes underlying this preventative or therapeutic action are also examined. We used PubMed, Scopus, Google Scholar, and the WHO site to perform our review. The anti-SARS-CoV-2 impacts of various herbal extracts and purified compounds may be mediated via direct prevention of viral replication or entrance. Interestingly, certain items might avert SARS-CoV-2 from infecting human cells by blocking the ACE-2 protein or the serine protease TMPRRS2. Natural products have also been stated to suppress proteins intricate in the virus life cycle, like papain-like and chymotrypsin-like proteases. To conclude, natural products can be used alone or in combination as remedies or treatments for COVID-19. In addition, their compositions may provide insight into the development of effective and reliable antiviral drugs.

5.
Molecules ; 27(11)2022 Jun 04.
Article in English | MEDLINE | ID: covidwho-1892926

ABSTRACT

Withania aristata (Aiton) Pauquy, a medicinal plant endemic to North African Sahara, is widely employed in traditional herbal pharmacotherapy. In the present study, the chemical composition, antioxidant, antibacterial, and antifungal potencies of extract from the roots of Withania aristata (Aiton) Pauquy (RWA) against drug-resistant microbes were investigated. Briefly, RWA was obtained by maceration with hydro-ethanol and its compounds were identified by use of high-performance liquid chromatography (HPLC). The antioxidant activity of RWA was determined by use of ferric-reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and total antioxidant capacity (TAC). The evaluation of the antimicrobial potential of RWA was performed against drug-resistant pathogenic microbial strains of clinical importance by use of the disc diffusion agar and microdilution assays. Seven compounds were identified in RWA according to HPLC analysis, including cichoric acid, caffeic acid, apigenin, epicatechin, luteolin, quercetin, and p-catechic acid. RWA had excellent antioxidant potency with calculated values of 14.0 ± 0.8 µg/mL (DPPH), 0.37 ± 0.08 mg/mL (FRAP), 760 ± 10 mg AAE/g (TAC), and 81.4% (ß-carotene). RWA demonstrated good antibacterial potential against both Gram-negative and Gram-positive bacteria, with inhibition zone diameters ranging from 15.24 ± 1.31 to 19.51 ± 0.74 mm, while all antibiotics used as drug references were infective, except for Oxacillin against S. aureus. Results of the minimum inhibitory concentration (MIC) assay against bacteria showed that RWA had MIC values ranging from 2.13 to 4.83 mg/mL compared to drug references, which had values ranging from 0.031 ± 0.003 to 0.064 ± 0.009 mg/mL. Similarly, respectable antifungal potency was recorded against the fungal strains with inhibition zone diameters ranging from 25.65 ± 1.14 to 29.00 ± 1.51 mm compared to Fluconazole, used as a drug reference, which had values ranging from 31.69 ± 1.92 to 37.74 ± 1.34 mg/mL. Results of MIC assays against fungi showed that RWA had MIC values ranging from 2.84 ± 0.61 to 5.71 ± 0.54 mg/mL compared to drug references, which had values ranging from 2.52 ± 0.03 to 3.21 ± 0.04 mg/mL. According to these outcomes, RWA is considered a promising source of chemical compounds with potent biological properties that can be beneficial as natural antioxidants and formulate a valuable weapon in the fight against a broad spectrum of pathogenic microbes.


Subject(s)
Anti-Infective Agents , Withania , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Antifungal Agents/pharmacology , Antioxidants/chemistry , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Staphylococcus aureus , Withania/chemistry
6.
Front Biosci (Landmark Ed) ; 27(5): 152, 2022 05 11.
Article in English | MEDLINE | ID: covidwho-1876485

ABSTRACT

BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. METHODS: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. RESULTS: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. CONCLUSIONS: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.


Subject(s)
COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19 Vaccines , Humans , SARS-CoV-2
7.
Saudi Pharm J ; 30(7): 979-1002, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1867429

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a more severe strain of coronavirus (CoV) that was first emerged in China in 2019. Available antiviral drugs could be repurposed and natural compounds with antiviral activity could be safer and cheaper source of medicine for SARS-CoV-2. 78 natural antiviral compounds database was identified from literature and virtual screening technique was applied to identify potential 3-chymotrypsin-like protease (3CLpro) inhibitors. Molecular docking studies were conducted to analyze the main protease (3CLpro) and inhibitors interactions with key residues of active site of target protein (PDB ID: 6LU7), active site constitute the part of active domain I and II of 3CLpro. 10 compounds with highest dock score were subjected to calculate ADMET parameters to figure out drug-likeness. Molecular dynamic (MD) simulation of the selected lead was performed by Amber simulation package to understand the conformational changes in docked complex. MD simulations analysis (RMSD, RMSF, Rg, BF, HBs, and SASA plots) of lead bounded with 3CLpro, hence revealed the important structural turns and twists during MD simulations from 0 to 100 ns. MM-PBSA/GBSA methods has also been applied for the estimation binding free energy (BFE) of the selected lead-complex. The present study has identified lead compound "Forsythoside A" an active extract of Forsythia suspense as SARS-CoV-2 3CLpro inhibitor that can block the viral replication and translation. Structural analysis of target protein and lead compound performed in this study could contribute to the development of potential drug against SARS-CoV-2 infection.

8.
Computational and Structural Biotechnology Journal ; 20:1306-1344, 2022.
Article in English | Web of Science | ID: covidwho-1850919

ABSTRACT

The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a long pandemic, with numerous cases and victims worldwide and enormous consequences on social and economic life. Although vaccinations have proceeded and provide a valuable shield against the virus, the approved drugs are limited and it is crucial that further ways to combat infection are developed, that can also act against potential mutations. The main protease (Mpro) of the virus is an appealing target for the development of inhibitors, due to its importance in the viral life cycle and its high conservation among different coronaviruses. Several compounds have shown inhibitory potential against Mpro, both in silico and in vitro, with few of them also having entered clinical trials. These candidates include: known drugs that have been repurposed, molecules specifically designed based on the natural substrate of the protease or on structural moieties that have shown high binding affinity to the protease active site, as well as naturally derived compounds, either isolated or in plant extracts. The aim of this work is to collectively present the results of research regarding Mpro inhibitors to date, focusing on the function of the compounds founded by in silico simulations and further explored by in vitro and in vivo assays. Creating an extended portfolio of promising compounds that may block viral replication by inhibiting Mpro and by understanding involved structure-activity relationships, could provide a basis for the development of effective solutions against SARS-CoV-2 and future related outbreaks. (c) 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

9.
J Biomol Struct Dyn ; : 1-16, 2022 May 09.
Article in English | MEDLINE | ID: covidwho-1830493

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. This virus has a high mismatch repair proofreading ability due to its unique exonuclease activity, making it knotty to treat. The nucleocapsid protein can serve as a potential antiviral drug target, as this protein is responsible for multiple captious functions during the viral life cycle. Herein, we have investigated the potential to repurpose active antiviral compounds of plant origins for treating the SARS-CoV-2 infection. In the present study, we followed the molecular docking methodology to screen druggable natural plants' active compounds against the nucleocapsid protein of SARS-CoV-2. The virtual screening of all 68 compounds revealed that the top seven active compounds, such as withanolide D, hypericin, silymarin, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein, exhibit good binding affinity with druggable ADME properties, toxicity, and Pass prediction. The stability of the docked complexes was studied by conducting molecular simulations of 100 ns. MM-GBSA calculated the binding free energy uncovered that withanolide D, hypericin, and silymarin result in highly stable binding conformations in three different sites of the nucleocapsid protein. However, further investigation is needed in order to validate the candidacy of these inhibitors for clinical trials. HighlightsNatural plants' active compounds may aid in the inhibition of SARS-CoV-2 replication and COVID-19 therapeutics.Hypericin, silymarin, withanolide D, oxyacanthine, withaferin A, Acetyl aleuritolic acid, and rhein are effective against SARS-CoV-2 N protein.Studied natural plants' active compounds could be useful against COVID-19 and its associated organs comorbidities.ADMET properties of selected compounds favor these compounds as druggable candidates.Communicated by Ramaswamy H. Sarma.

10.
2nd International Conference on Advanced Research in Computing, ICARC 2022 ; : 320-325, 2022.
Article in English | Scopus | ID: covidwho-1831765

ABSTRACT

The SARS-COV-2 become a global pandemic causing significant mortality and morbidity all around the world. Until now there are no effective drugs or vaccines available against SARS-CoV-2. In this regard, medicinal plants captured enormous attention, as natural products are safe and easily available bioactive compounds in which maintain the disease homeostasis. Amongst, natural compounds of Coriandrum sativum L (coriander) have proved to be effective in viral infection, as they possess antiviral and anti-inflammatory activities. However, molecular regulation of such bioactivities remains elusive. We performed molecular docking analyses using AutoDock Vina to investigate the potential inhibitory activities of the seven natural compounds of coriander (limonene, geraniol, gamma-terpinene, geranyl acetate, caffeic acid, ferulic acid, gallic acid) against the essential proteins of SARS-CoV-2 (main protease (Mpro), nonstructural protein-13 (NSP-13), Papaine like protease (PLpro) and RNA dependent RNA polymerase(RdRp)) together with two main inflammatory proteins ( cyclooxygenase-2 (COX-2) and interleukin-6 (IL- 6)). The empirical and knowledge-based algorithm of AutoDock Vina was utilized to calculate free binding energies of ligands and BIOVIA discovery studio 2020 tool was used to visualize docking results. Our results reveal that gallic acid has a strong binding affinity to Mpro (-5.8 kcal/mol) and NSP13 (-7.0 kcal/mol) forming five and three conventional hydrogen bonds respectively. Further, caffeic acid demonstrates a higher binding affinity to PLpro (-7.4 kcal/mol) and RdRp (-6.7 kcal/mol) while securing four and three conventional hydrogen bonds respectively. Interestingly, both COX-2 (-6.9 kcal/mol) and IL-6 (-6.3 kcal/mol) also show a higher binding affinity to gallic acids. In addition, gallic acid stabilizes three conventional hydrogen bonds with COX-2 whereas it forms four conventional hydrogen bonds with IL-6. Further, drug-likeness properties of gallic acid and caffeic acid were determined using the SWISSADME server. Our results show that both gallic acid and caffeic do not violate Lipinski rules suggesting these compounds as new antiviral and anti-inflammatory drug candidates for SARS-CoV-2. © 2022 IEEE.

11.
Latin American Journal of Pharmacy ; 41(3):701-718, 2022.
Article in English | Web of Science | ID: covidwho-1749250

ABSTRACT

Coronavirus disease (COVID-19) is caused by SA RS-CoV-2 and represents the causative agent of a potentially lethal disease. COVID-19 has been described as a significant global public health pandemic by the World Health Organization due to its high mortality rate, rapid spread, and the lack of drugs. Active antiviral drugs are desperately needed to combat the potential return of severe acute respiratory syndrome (SARS). In this study, we selected 39 natural compounds present in plants, algae, and sponges with antiviral activity. Molecular docking was used to screen the compounds' activity on SARS- CoV-2 RNA-dependent-RNA polymerase, receptor-binding domain (RBD), and the human ACE2 receptor. Compounds with binding energy less than -6.5 kcal/mol enter pre-clinical testing using insilco ADME/Tox (absorption, distribution, metabolism, excretion, and toxicity). We found eight potential SA RS-CoV-2 inhibitors: (glycyrrhizin, rutin, baicalin, 1, 6-di-O- galloyl-beta-D-glucose, pyropheophorbide A, pheophorbide A, beta-Sitosterol, and vitexin). These outcomes indicate that these compounds could be potential candidates to be utilized for the design and production of the anti-SARS-CoV-2 drug.

12.
Current Chemical Biology ; 15(3):205-214, 2021.
Article in English | Scopus | ID: covidwho-1745204

ABSTRACT

The virus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) causes COVID 19 (Corona Virus Disease 19), a global pandemic with multi-organ failure, resulting in high morbidity and mortality. Some individuals are more vulnerable than others and have deleterious consequences following COVID-19. It has been postulated that Heme oxygenase-1 (HO-1) reduction and free heme may contribute to many of the inflammatory phenomena observed in COVID-19 patients. Therefore, HO-1 inducers could prove to be potential therapeutic or preventive agents for COVID 19. Many of the natural compounds present in fruits and vegetables, such as polyphenols, were able to induce HO-1. The aim of this review is to focus on the main foods containing bioactive compounds able to induce HO-1 for an informed choice of foods to use to counteract damage from SARS-CoV-2 infection. © 2021 Bentham Science Publishers.

13.
Comput Struct Biotechnol J ; 20: 1306-1344, 2022.
Article in English | MEDLINE | ID: covidwho-1739656

ABSTRACT

The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a long pandemic, with numerous cases and victims worldwide and enormous consequences on social and economic life. Although vaccinations have proceeded and provide a valuable shield against the virus, the approved drugs are limited and it is crucial that further ways to combat infection are developed, that can also act against potential mutations. The main protease (Mpro) of the virus is an appealing target for the development of inhibitors, due to its importance in the viral life cycle and its high conservation among different coronaviruses. Several compounds have shown inhibitory potential against Mpro, both in silico and in vitro, with few of them also having entered clinical trials. These candidates include: known drugs that have been repurposed, molecules specifically designed based on the natural substrate of the protease or on structural moieties that have shown high binding affinity to the protease active site, as well as naturally derived compounds, either isolated or in plant extracts. The aim of this work is to collectively present the results of research regarding Mpro inhibitors to date, focusing on the function of the compounds founded by in silico simulations and further explored by in vitro and in vivo assays. Creating an extended portfolio of promising compounds that may block viral replication by inhibiting Mpro and by understanding involved structure-activity relationships, could provide a basis for the development of effective solutions against SARS-CoV-2 and future related outbreaks.

14.
Turk J Pharm Sci ; 19(1): 93-100, 2022 02 28.
Article in English | MEDLINE | ID: covidwho-1715952

ABSTRACT

Objectives: Unavailability of potential drugs/vaccines in the outbreak of the pandemic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) have devastated the human population globally. Several druggable targets have been analyzed against different viral proteins such as the spike protein. The study aims to explore the potential of natural compounds as an effective drug against a novel nsp10-nsp16 complex of SARS-CoV-2 using in silico approaches. Materials and Methods: In silico screening (Docking analysis) was performed for 10 shortlisted natural compounds viz. allicin, ajoene, carvacrol, coumarin, curcumin, menthol, eugenol, theaflavin, ursolic acid, and catechin against a novel target of SARS-CoV-2, that has been anticipated to provide valuable lead molecules and potentially druggable compounds for the treatment of SARS-CoV-2. Results: Theaflavin and catechin, the natural components of black tea and green tea, out of 10 shortlisted compounds have shown excellent performance in our docking studies with the minimum binding energy of -11.8 kcal/mol and -9.2 kcal/mol respectively, against a novel nsp10-nsp16 complex of SARS-CoV-2 that indicates their potential for inhibitory molecular interactions against the virus to assist rapid drug designing from natural products. Conclusion: Either consumption of black tea and green tea or repurposing them as drug candidates may help individuals to fight against SARS-CoV-2, subject to their in vivo and in vitro further experimental validations.

15.
J Food Biochem ; 46(5): e14085, 2022 05.
Article in English | MEDLINE | ID: covidwho-1673175

ABSTRACT

SARS-CoV-2 wreaks havoc around the world, triggering the COVID-19 pandemic. It has been confirmed that the endoribonuclease NSP15 is crucial to the viral replication, and thus identified as a potential drug target against COVID-19. The NSP15 protein was used as the target to conduct high-throughput virtual screening on 30,926 natural products from the NPASS database to identify potential NSP15 inhibitors. And 100 ns molecular dynamics simulations were performed on the NSP15 and NSP15-NPC198199 system. In all, 10 natural products with high docking scores with NSP15 protein were obtained, among which compound NPC198199 scored the highest. The analysis of the binding mode between NPC198199 and NSP15 found that NPC198199 would form H-bond interactions with multiple key residues at the catalytic site. Subsequently, a series of post-dynamics simulation analyses (including RMSD, RMSF, PCA, DCCM, RIN, binding free energy, and H-bond occupancy) were performed to further explore inhibitory mechanism of compound NPC198199 on NSP15 protein at the molecular level. The research strongly indicates that the 10 natural compounds screened can be used as potential inhibitors of NSP15, and provides valuable information for the subsequent drug discovery of anti-SARS-CoV-2. PRACTICAL APPLICATIONS: Natural products play an important role in the treatment of many difficult diseases. In this study, high-throughput virtual screening technology was used to screen the natural product database to obtain potential inhibitors against endoribonuclease NSP15. The binding mechanism between natural products and NSP15 was investigated at the molecular level by molecular dynamics technology so that it is expected to become candidate drugs for the treatment of SARS-CoV-2. We hope that our research can provide new clue to combat COVID-19 and overcome the epidemic situation as soon as possible.


Subject(s)
Antiviral Agents , Biological Products , Endoribonucleases , SARS-CoV-2 , Viral Nonstructural Proteins , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Endoribonucleases/antagonists & inhibitors , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2/drug effects , Viral Nonstructural Proteins/antagonists & inhibitors
16.
J Microbiol ; 60(3): 347-354, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1652455

ABSTRACT

Coronavirus disease (COVID-19) can cause critical conditions that require efficient therapeutics. Several medicines are derived from plants, and researchers are seeking natural compounds to ameliorate the symptoms of COVID-19. Viral enzymes are popular targets of antiviral medicines; the genome of coronaviruses encodes several enzymes, including RNA-dependent RNA polymerase and viral proteases. Various screening systems have been developed to identify potential inhibitors. In this review, we describe the natural compounds that have been shown to exert inhibitory effects on coronavirus enzymes. Although computer-aided molecular structural studies have predicted several antiviral compound candidates, the current review focuses on experimentally proven natural compounds.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 , Enzyme Inhibitors , Phytochemicals/pharmacology , COVID-19/drug therapy , Enzyme Inhibitors/pharmacology , Humans , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology
17.
Bulletin of the University of Karaganda-Chemistry ; - (103):37-46, 2021.
Article in English | Web of Science | ID: covidwho-1614534

ABSTRACT

COVID-19 cases increase at a high rate and become dangerous in recent months. As a consequence, some healthcare and research organizations are attempting to find an effective cure for the COVID-19 outbreak. Many natural products have been reported to have powerful activity against COVID-19 in recent research studies. The primary aim of this article is to establish natural bioactive compounds with suitable antiviral properties. Lui et al. have reported in their study that SARS-Cov-2 main protease is present in a crystalline structure known as a novel therapeutic drug target. It is important to inhibit SARS-Cov-2 main protease to stop the replication of viral proteins. In this study natural compounds were screened using molecular modeling techniques to investigate probable bioactive compounds that block SARS-Cov-2. From these studies many natural compounds were found to have the potential to interact with viral proteins and show inhibitory activity against COVID-19 main protease (Mpro) and these natural compounds were also compared to known antiviral drugs such as Saquinavir and Remdesivir. Besides that, additional research is needed before these potential leads can be developed into natural therapeutic agents against COVID-19 to fight the epidemic.

18.
All Life ; 14(1):1100-1128, 2021.
Article in English | Web of Science | ID: covidwho-1585212

ABSTRACT

The novel beta-coronavirus, SARS-CoV-2, responsible for the coronavirus disease 2019 (COVID-19) emerged in China in December 2019. Due to its high transmission and infection rate, it has spread around the world and has transformed into a ravaging global pandemic with enormously unprecedented impacts globally on human, social, and economic health. Just like SARS-CoV and MERS-CoV, there is no specific antiviral drug for its treatment. The only available therapeutics are supportive and symptom-based. Thus, scientists are harnessing various strategies to expedite drug development. One such approach is drug repurposing through computational screening of phytocompounds, which leverages proteins that are essential for the entry, replication, pathogenesis, assembly, and release of SARS-CoV-2. Here, we review the available literature on molecular docking of phytoligands against SARS-CoV-2 integral proteins, in a bid to update our current knowledge and identify the most promising molecules. The overwhelming majority of the promising lead compounds are either phenolics or terpenoids. Furthermore, of the elucidated SARS-CoV-2 targets, the main protease (3CL(pro)) appears as one of the most attractive druggable targets. Notably, compounds such as rutin, quercetin, luteolin, neoandrographolide, curcumin, and others with evident anti-inflammatory benefits, in addition to their predicted anti-SARS-CoV-2 properties, deserve further studies to validate their activity.

19.
Comput Struct Biotechnol J ; 19: 6431-6455, 2021.
Article in English | MEDLINE | ID: covidwho-1587985

ABSTRACT

The rational search for allosteric modulators and the allosteric mechanisms of these modulators in the presence of mutations is a relatively unexplored field. Here, we established novel in silico approaches and applied them to SARS-CoV-2 main protease (Mpro) as a case study. First, we identified six potential allosteric modulators. Then, we focused on understanding the allosteric effects of these modulators on each of its protomers. We introduced a new combinatorial approach and dynamic residue network (DRN) analysis algorithms to examine patterns of change and conservation of critical nodes, according to five independent criteria of network centrality. We observed highly conserved network hubs for each averaged DRN metric on the basis of their existence in both protomers in the absence and presence of all ligands (persistent hubs). We also detected ligand specific signal changes. Using eigencentrality (EC) persistent hubs and ligand introduced hubs we identified a residue communication path connecting the allosteric binding site to the catalytic site. Finally, we examined the effects of the mutations on the behavior of the protein in the presence of selected potential allosteric modulators and investigated the ligand stability. One crucial outcome was to show that EC centrality hubs form an allosteric communication path between the allosteric ligand binding site to the active site going through the interface residues of domains I and II; and this path was either weakened or lost in the presence of some of the mutations. Overall, the results revealed crucial aspects that need to be considered in rational computational drug discovery.

20.
Pharmaceuticals (Basel) ; 14(12)2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1580535

ABSTRACT

The lack of medication to treat COVID-19 is still an obstacle that needs to be addressed by all possible scientific approaches. It is essential to design newer drugs with varied approaches. A receptor-binding domain (RBD) is a key part of SARS-CoV-2 virus, located on its surface, that allows it to dock to ACE2 receptors present on human cells, which is followed by admission of virus into cells, and thus infection is triggered. Specific receptor-binding domains on the spike protein play a pivotal role in binding to the receptor. In this regard, the in silico method plays an important role, as it is more rapid and cost effective than the trial and error methods using experimental studies. A combination of virtual screening, molecular docking, molecular simulations and machine learning techniques are applied on a library of natural compounds to identify ligands that show significant binding affinity at the hydrophobic pocket of the RBD. A list of ligands with high binding affinity was obtained using molecular docking and molecular dynamics (MD) simulations for protein-ligand complexes. Machine learning (ML) classification schemes have been applied to obtain features of ligands and important descriptors, which help in identification of better binding ligands. A plethora of descriptors were used for training the self-organizing map algorithm. The model brings out descriptors important for protein-ligand interactions.

SELECTION OF CITATIONS
SEARCH DETAIL