scholarly journals An Overview of COVID-19 and the Potential Plant Harboured Secondary Metabolites against SARS-CoV-2: A Review

2021 ◽  
Vol 15 (3) ◽  
pp. 1059-1071
Author(s):  
C.T. Swamy
Keyword(s):  
Secondary Metabolites ◽  
Pulmonary Veins ◽  
Experimental Studies ◽  
Plant Metabolites ◽  
Primary And Secondary Metabolites ◽  
Quinoline Alkaloids ◽  
Main Protease ◽  
Current Scenario ◽  
Novel Coronavirus

The SARS-CoV-2 virus causes COVID-19, a pandemic disease, and it is called the novel coronavirus. It belongs to the Coronaviridae family and has been plagued the world since the end of 2019. Viral infection to the lungs causes fluid filling and breathing difficulties, which leads to pneumonia. Pneumonia progresses to ARDS (Acute Respiratory Distress Syndrome), in which fluid fills the air sac and seeps from the pulmonary veins. In the current scenario, several vaccines have been used to control the pandemic worldwide. Even though vaccines are available and their effectiveness is short, it may be helpful to curb the pandemic, but long-term protection is inevitable when we look for other options. Plants have diversified components such as primary and secondary metabolites. These molecules show several activities such as anti-microbial, anti-cancer, anti-helminthic. In addition, these molecules have good binding ability to the SARS-CoV-2 virus proteins such as RdRp (RNA-dependent RNA polymerase), Mpro (Main Protease), etc. Therefore, these herbal molecules could probably be used to control the COVID-19. However, pre-requisite tests, such as cytotoxicity, in vivo, and human experimental studies, are required before plant molecules can be used as potent drugs. Plant metabolites such as alkaloids, isoquinoline ß-carboline, and quinoline alkaloids such as skimmianine, quinine, cinchonine, and dictamine are present in plants and used in a traditional medicinal system.

scholarly journals Virtual Screening of Potential Inhibitors for SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Carlos Javier Alméciga-Díaz ◽  
Luisa N. Pimentel-Vera ◽  
Angela Caro ◽  
Angela Mosquera ◽  
Camilo Andrés Castellanos Moreno ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Clinical Information ◽  
Virus Genome ◽  
Pharmacological Agents ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors

Coronavirus Disease 2019 (Covid-19) was first described in December 2019 in Wuhan, Hubei Province, China; and produced by a novel coronavirus designed as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 has become a pandemic reaching over 1.3 million confirmed cases and 73,000 deaths. Several efforts have been done to identify pharmacological agents that can be used to treat patients and protect healthcare professionals. The sequencing of the virus genome not only has offered the possibility to develop a vaccine, but also to identified and characterize the virus proteins. Among these proteins, main protease (Mpro) has been identified as a potential therapeutic target, since it is essential for the processing other viral proteins. Crystal structures of SARS-CoV-2 Mpro and inhibitors has been described during the last months. To describe additional compounds that can inhibit SARS-CoV-2 Mpro, in this study we performed a molecular docking-based virtual screening against a library of experimental and approved drugs. Top 10 hits included Pictilisib, Nimorazole, Ergoloid mesylates, Lumacaftor, Cefuroxime, Cepharanhine, and Nilotinib. These compounds were predicted to have higher binding affinity for SARS-CoV-2 Mpro than previously reported inhibitors for this protein, suggesting a higher potential to inhibit virus replication. Since the identified drugs have both pre-clinical and clinical information, we consider that these results may contribute to the identification of treatment alternative for Covid-19. Nevertheless, in vitro and in vivo confirmation should be performed before these compounds could be translated to the clinic.

scholarly journals MicroRNAs and long non-coding RNAs as potential candidates to target specific motifs of SARS-CoV-2

2020 ◽  
Author(s):  
Lucia Natarelli ◽  
Luca Parca ◽  
Fabio Virgili ◽  
Tommaso Mazza ◽  
Christian Weber ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Specific Treatment ◽  
Leader Sequence ◽  
The Novel ◽  
Health Crisis ◽  
Global Pandemic ◽  
Pulmonary Arterial ◽  
Non Coding Rnas ◽  
Novel Coronavirus

Abstract The novel Coronavirus, SARS-CoV-2 disease (COVID-19) was defined as a global pandemic and induced a severe public health crisis in 2020. Covid-19 viral infection targets the human respiratory system and, at present, no specific treatment has been identified even though certain drugs have been studied and considered apparently effective in viral progression by reducing the complications in the lung epithelium. Researchers and clinicians are still struggling to find a vaccine or a specific innovative therapeutic strategy to counter COVID-19 infection.Here we describe our study indicating that SARS-CoV-2 genome contains motif sequences in the 5´UTR leader sequence that can be selectively recognized by specific human non-coding RNAs (ncRNAs), such as micro and long non-coding RNAs (miRNAs and lncRNA). Notably, some of these ncRNAs have been already utilized as oligo-based drugs in pulmonary and virus-associated diseases. We identified three selective motifs at the 5´UTR leader sequence of SARS-CoV-2 that allow viral recognition and binding of a specific group of miRNAs, some of them characterized by “GU” seed alignments. Additionally, one seed motif within miRNAs has been found to be able to bind the 5’UTR leader sequence. Among miRNAs having thermodynamically stable binding site against leader sequence and that are able interacted with Spike transcript some are involved in pulmonary arterial hypertension and anti-viral response, i.e. miR-204, miR-3661, and miR-1343. Moreover, several miRNA candidates have been already validated in vivo and specific oligo sequence are indeed available for their inhibition or overexpression.Four lncRNAs (H19, Hotair, Fendrr, and LINC05) directly interact with spike transcript (mRNA) and viral genome.In conclusion, we suggest that specific miRNAs and lncRNAs can be potential candidates to design oligonucleotide-drugs to treat COVID-19 and that our study can provide candidate hypothesis to be eventually tested in further experimental studies.

scholarly journals Molecular Docking of Olea europaea and Curcuma Longa Compounds as Potential Drug Agents for Targeting Main-Protease of SARS-nCoV2

2020 ◽  
Author(s):  
Rashid Saif ◽  
Muhammad Hassan Raza ◽  
Talha Rehman ◽  
Muhammad Osama Zafar ◽  
Saeeda Zia ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Curcuma Longa ◽  
Experimental Studies ◽  
Md Simulations ◽  
Binding Energies ◽  
Target Protein ◽  
Target Proteins ◽  
Main Protease

<p>One of the main reasons of rapidly growing cases of COVID-19 pandemic is the unavailability of approved therapeutic agents. Therefore, it is urgently required to find out the best drug/vaccine by all means. Aim of the current study is to test the anti-viral drug potential of many of the available olive and turmeric compounds that can be used as potential inhibitors against one of the target proteins of SARS-nCoV2 named Main protease (Mpro/3clpro). Molecular docking of thirty olive and turmeric compounds with target protein was performed using Molecular Operating Environment (MOE) software to determine the best ligand-protein interaction energies. The structural information of the viral target protein M pro/3CL pro and ligands were taken from PDB and PubChem database respectively. Out of the thirty drug agents, 6 ligands do not follow the Lipinski rule of drug likeliness by violating two or more rules while remaining 24 obey the rules and included for the downstream analysis. Ten ligands from olive and four from turmeric gave the best lowest binding energies, which are Neuzhenide, Rutin, Demethyloleoeuropein, Oleuropein, Luteolin-7-rutinoside, Ligstroside, Verbascoside, Luteolin-7-glucoside, Cosmosin, Curcumin, Tetrehydrocurcumin, Luteolin-4'-o-glucoside, Demethoxycurcumin and Bidemethoxycurcumin with docking scores of -10.91, -9.49, -9.48, -9.21, -9.18, -8.72, -8.51, -7.68, -7.67, -7.65, -7.42, -7.25, -7.02 and - 6.77 kcal/mol respectively. Our predictions suggest that these ligands have the potential inhibitory effects of M pro of SARS-nCoV2, so, these herbal plants would be helpful in harnessing COVID-19 infection as home remedy with no serious known side effects. Further, in-silico MD simulations and in-vivo experimental studies are needed to validate the inhibitory properties of these compounds against the current and other target proteins in SARS-nCoV2.<br></p>

scholarly journals Mechanistic Insights into the Inhibition of SARS-CoV-2 Main Protease by Clovamide and Its Derivatives: In Silico Studies

Biophysica ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 377-404
Author(s):  
Naike Ye ◽  
Francesco Caruso ◽  
Miriam Rossi
Keyword(s):  
Density Functional ◽  
Experimental Studies ◽  
Radical Scavenging ◽  
The Body ◽  
Phenolic Fraction ◽  
Main Protease ◽  
In Silico Studies ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Novel Coronavirus

The novel coronavirus SARS-CoV-2 Main Protease (Mpro) is an internally encoded enzyme that hydrolyzes the translated polyproteins at designated sites. The protease directly mediates viral replication processes; hence, a promising target for drug design. Plant-based natural products, especially polyphenols and phenolic compounds, provide the scaffold for many effective antiviral medications, and have recently been shown to be able to inhibit Mpro of SARS-CoV-2. Specifically, polyphenolic compounds found in cacao and chocolate products have been shown by recent experimental studies to have strong inhibitory effects against Mpro activities. This work aims to uncover the inhibition processes of Mpro by a natural phenolic compound found in cacao and chocolate products, clovamide. Clovamide (caffeoyl-DOPA) is a naturally occurring caffeoyl conjugate that is found in the phenolic fraction of Theobroma Cacao L. and a potent radical-scavenging antioxidant as suggested by previous studies of our group. Here, we propose inhibitory mechanisms by which clovamide may act as a Mpro inhibitor as it becomes oxidized by scavenging reactive oxygen species (ROS) in the body, or becomes oxidized as a result of enzymatic browning. We use molecular docking, annealing-based molecular dynamics, and Density Functional Theory (DFT) calculations to study the interactions between clovamide with its derivatives and Mpro catalytic and allosteric sites. Our molecular modelling studies provide mechanistic insights of clovamide inhibition of Mpro, and indicate that clovamide may be a promising candidate as a drug lead molecule for COVID-19 treatments.

scholarly journals Molecular Docking of Olea europaea and Curcuma Longa Compounds as Potential Drug Agents for Targeting Main-Protease of SARS-nCoV2

2020 ◽  
Author(s):  
Rashid Saif ◽  
Muhammad Hassan Raza ◽  
Talha Rehman ◽  
Muhammad Osama Zafar ◽  
Saeeda Zia ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Curcuma Longa ◽  
Experimental Studies ◽  
Md Simulations ◽  
Binding Energies ◽  
Target Protein ◽  
Target Proteins ◽  
Main Protease

<p>One of the main reasons of rapidly growing cases of COVID-19 pandemic is the unavailability of approved therapeutic agents. Therefore, it is urgently required to find out the best drug/vaccine by all means. Aim of the current study is to test the anti-viral drug potential of many of the available olive and turmeric compounds that can be used as potential inhibitors against one of the target proteins of SARS-nCoV2 named Main protease (Mpro/3clpro). Molecular docking of thirty olive and turmeric compounds with target protein was performed using Molecular Operating Environment (MOE) software to determine the best ligand-protein interaction energies. The structural information of the viral target protein M pro/3CL pro and ligands were taken from PDB and PubChem database respectively. Out of the thirty drug agents, 6 ligands do not follow the Lipinski rule of drug likeliness by violating two or more rules while remaining 24 obey the rules and included for the downstream analysis. Ten ligands from olive and four from turmeric gave the best lowest binding energies, which are Neuzhenide, Rutin, Demethyloleoeuropein, Oleuropein, Luteolin-7-rutinoside, Ligstroside, Verbascoside, Luteolin-7-glucoside, Cosmosin, Curcumin, Tetrehydrocurcumin, Luteolin-4'-o-glucoside, Demethoxycurcumin and Bidemethoxycurcumin with docking scores of -10.91, -9.49, -9.48, -9.21, -9.18, -8.72, -8.51, -7.68, -7.67, -7.65, -7.42, -7.25, -7.02 and - 6.77 kcal/mol respectively. Our predictions suggest that these ligands have the potential inhibitory effects of M pro of SARS-nCoV2, so, these herbal plants would be helpful in harnessing COVID-19 infection as home remedy with no serious known side effects. Further, in-silico MD simulations and in-vivo experimental studies are needed to validate the inhibitory properties of these compounds against the current and other target proteins in SARS-nCoV2.<br></p>

scholarly journals Phytochemicals of Rhus spp. as Potential Inhibitors of the SARS-CoV-2 Main Protease: Molecular Docking and Drug-Likeness Study

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yousery E. Sherif ◽  
Sami A. Gabr ◽  
Nasser M. Hosny ◽  
Ahmad H. Alghadir ◽  
Rayan Alansari
Keyword(s):  
Molecular Docking ◽  
Specific Treatment ◽  
Polyphenolic Compounds ◽  
Protease Enzyme ◽  
Main Protease ◽  
Synthetic Accessibility ◽  
Novel Coronavirus ◽  
Potential Inhibitors

Background. The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. Aim. In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). Methods. 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. Results. The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. Conclusion. Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.

scholarly journals Molecular docking and dynamic simulation of Olea europaea and Curcuma Longa compounds as potential drug agents for targeting Main-Protease of SARS-nCoV2

2021 ◽  
Author(s):  
Rashid Saif ◽  
Muhammad Hassan Raza ◽  
Talha Rehman ◽  
Muhammad Osama Zafar ◽  
Saeeda Zia ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Curcuma Longa ◽  
Experimental Studies ◽  
Dynamics Simulation ◽  
Target Proteins ◽  
Main Protease ◽  
The Stability ◽  
Downstream Analysis ◽  
Potential Inhibitors

<p></p><p>One of the main reasons of rapidly growing cases of COVID-19 pandemic is the unavailability of approved therapeutic agents. Therefore, it is urgently required to find out the best drug by all means. Aim of the current study is to test the anti-viral drug potential of many of the available olive and turmeric compounds that can be used as potential inhibitors against one of the target proteins of SARS-nCoV2 named Main protease (Mpro/3CLpro). Molecular docking of thirty olive and turmeric compounds with target protein was performed using Molecular Operating Environment (MOE) software, out of these 19 ligands were selected for redocking using PyRx to validate MOE results and to determine the best ligand-protein interaction energies. Molecular dynamics simulation was performed on best 7 docked complexes by NAMD/VMD to determine the stability of the ligand-protein complex. Out of the thirty drug agents, 6 ligands do not follow the Lipinski rule of drug likeliness by violating two or more rules while remaining 24 obey the rules and included for the downstream analysis. We found that Demethyloleoeuropein, Oleuropein, Rutin, Neuzhenide, Luteolin-7-rutinoside, Curcumin and Tetrehydrocurcumin gave best docking score and form much stable complexes during simulation. Our predictions suggest that these ligands have the potential inhibitory effects on Mpro of SARS-nCoV2, so, these herbal plants would be helpful in harnessing COVID-19 infection as home remedy with no serious known side effects. Further, in-vivo experimental studies are needed to validate the inhibitory properties of these compounds against the current and other target proteins in SARS-nCoV2.<b></b></p><br><p></p>

scholarly journals Plant Metabolites Drive Different Responses in Caterpillars of Two Closely Related Helicoverpa Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Longlong Sun ◽  
Wenhua Hou ◽  
Jiajia Zhang ◽  
Yuli Dang ◽  
Qiuyun Yang ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Host Plants ◽  
Plant Secondary Metabolites ◽  
Diet Breadth ◽  
Insect Species ◽  
Plant Metabolites ◽  
Adaptation Mechanism ◽  
Primary And Secondary Metabolites ◽  
The Difference ◽  
Generalist Insect

The host acceptances of insects can be determined largely by detecting plant metabolites using insect taste. In the present study, we investigated the gustatory sensitivity and feeding behaviors of two closely related caterpillars, the generalist Helicoverpa armigera (Hübner) and the specialist H. assulta (Guenée), to different plant metabolites by using the single sensillum recording technique and the dual-choice assay, aiming to explore the contribution of plant metabolites to the difference of diet breadth between the two species. The results depicted that the feeding patterns of caterpillars for both plant primary and secondary metabolites were significantly different between the two Helicoverpa species. Fructose, glucose, and proline stimulated feedings of the specialist H. assulta, while glucose and proline had no significant effect on the generalist H. armigera. Gossypol and tomatine, the secondary metabolites of host plants of the generalist H. armigera, elicited appetitive feedings of this insect species but drove aversive feedings of H. assulta. Nicotine and capsaicin elicited appetitive feedings of H. assulta, but drove aversive feedings of H. armigera. For the response of gustatory receptor neurons (GRNs) in the maxillary styloconic sensilla of caterpillars, each of the investigated primary metabolites induced similar responding patterns between the two Helicoverpa species. However, four secondary metabolites elicited different responding patterns of GRNs in the two species, which is consistent with the difference of feeding preferences to these compounds. In summary, our results of caterpillars’ performance to the plant metabolites could reflect the difference of diet breadth between the two Helicoverpa species. To our knowledge, this is the first report showing that plant secondary metabolites could drive appetitive feedings in a generalist insect species, which gives new insights of underscoring the adaptation mechanism of herbivores to host plants.

Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

2020 ◽  
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne ◽  
Uddhavesh Sonavane ◽  
Asheet Kumar Nath ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Drug Binding ◽  
Ensemble Docking ◽  
Drug Molecules ◽  
Drug Binding Site ◽  
Main Protease ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Markov State Modeling ◽  
Viral Polyprotein

<p>The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CL<sup>pro</sup> (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This <i>in-silico</i> ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.</p>

Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

2020 ◽  
Author(s):  
Micael Davi Lima de Oliveira ◽  
Kelson Mota Teixeira de Oliveira
Keyword(s):  
World Health Organisation ◽  
World Health ◽  
Lung Cells ◽  
The Novel ◽  
High Modulation ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Viral Receptors ◽  
Theoretical Results

According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.

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