COVID-19 Main Protease Research Articles

Curcumins and its derivatives as potential inhibitors of New Coronavirus (COVID-19) main protease: an in silico strategy

Coronavirus (COVID-19) disease outbreak caused a worldwide pandemic with a powerful lethal potential and still, there is no specific treatment to it. Natural bioactive molecules like curcumins were investigated in this work aiming to block the active site of COVID-19 Main protease (Mpro), since they present several biological activities, being more suitable in terms of fewer side effects, once this disease overloads the immune system of patients. Hereby, curcumin and several derivatives were screened for their ability to react with Mpro receptors (PDB: 6LU7). N3, Azithromycin (AZT), and Baracitinib (BRT) were evaluated as positive controls and in combined therapeutics possibilities with curcumins. N3, AZT, and BRT bound to different protein receptors, and also it was observed that N3 bound in the same site as hexahydrocurcumin and curcumin glucuronide bound at the AZT’s site and bisdemethoxycurcumin, curcumin, curcumin sulfate, cyclocurcumin, demethoxycurcumin, dihydrocurcumin and hexahydrocurcuminol bound at BRT’s site. All molecules analyzed have high force interaction fields. Once the viral activity is mainly intracellular, these compounds also were evaluated for their hydropathic abilities. All molecules were classified and considered capable of membrane cell invading. These results suggest that the therapeutic approach of the curcumin derivatives associated with AZT and the antiviral inhibitor N3 is promissory for future evaluation of their synergism in in vitro and in vivo tests to define their additional viability in the treatment of COVID-19.

Synthesis of pyrazolo[5',1':2,3]imidazo[1,5-c]quinazolin-6(5H)-ones and molecular docking study of their affinity against the COVID-19 main protease.

A novel series of fused pyrazolo[5′,1′:2,3]imidazo[1,5-c]quinazolin-6(5H)-ones were synthesized and their affinity against the COVID-19 main protease was investigated using molecular docking study and compared to that of some used standard clinical drugs. These compounds were obtained in good to excellent yields from 63 to 91% in the presence of 30 mol% catalyst in ethanol at reflux for 2 h through an efficient one-pot three-component reaction including an intramolecular rearrangement and a cyclization through intramolecular nucleophilic reaction. The results of in silico studies showed that electronegativity, resonance effects, hydrophobic interaction, halogen and hydrogen bonding had significant effects on the performance of these compounds as an inhibitor ligand. Also, these results indicated the proper affinity of these compounds against the COVID-19 main protease with excellent binding energies (especially 4r = −8.77, 4q = −8.73 and 4m = −8.63) in comparison to remdesivir, chloroquine, hydroxychloroquine, molnupiravir and nirmatrelvir drugs.

Therapeutic capability of five active compounds in typical African medicinal plants against main proteases of SARS-CoV-2 by computational approach

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a pandemic cause of Corona Virus Disease (COVID-19), that has claimed numerous human lives across the globe. Main protease being the active protein of SARS-CoV-2 requires urgent mitigating effect against the spread of the virus. The therapeutic roles of the active compounds present in ten typical African medicinal plants were investigated in this study. Five active compounds Curcuma longa (Curcumin and Bisdethoxy curcumin), Garcinia kola (kolaviron), Zingiber officinale (Gingerol) and Vernonia amygdalina (Artemisinin) were selected and docked against Main protease through receptor grid generation, protein ligand docking, receptor ligand complex pharmacophore and binding free energy. The results obtained revealed Curcumin had the highest binding score of −8.628 kcal/mol while artermisinin presented the least with −4.123 kcal/mol. The outcome of the pharmacokinetic prediction in this study revealed high transport capacity across the gastrointestinal tract and high blood brain barrier permeability for curcumin, bisdemethoxy curcumin, gingerol and artemisinin. The exemption is gingerol with low LD50 value (250 mg/kg), the LD50 of all active compounds ranged from 2000 to 4228 mg/kg. Adsorption, distribution, metabolism, excretion and toxicity (ADMET) properties exhibited by all compounds portrayed them as non-hepatotoxic, non-cytotoxic, non-mutagenic and non-carcinogenic. The active compounds exhibited drug-likeness features against Main protease of Covid-19.

Efficiency of curcuminoids against COVID-19 proteins and human ACE-2 receptor: A molecular docking study

COVID-19 is a deadly disease which has become a global issue in the recent years. At present, the whole world is trying to combat the disease and scientific communities are putting rigorous efforts in developing 100 per cent effective treatment. Though some synthetic drugs are efficient in controlling the COVID-19, they possess numerous side effects on human body. In these consequences, there is a global need to search for the natural agents that can act against COVID-19 as a precautionary measure which can improve our immunity and also to control the COVID-19 at various stages of infection. Curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are naturally derived plant compounds from turmeric rhizomes and are having the ability to fight against COVID-19. Earlier studies have focused on docking of curcuminoids against spike protein and main protease of COVID-19. In the present study, docking of curcuminoids against four COVID-19 proteins and one human receptor has been studied. The efficiency of curcuminoids was compared with that of synthetic drugs. Results clearly showed the potentiality of curcuminoids against COVID-19 and can be used as an alternative to the existing synthetic drugs after sufficient clinical trials.

Microwave-assisted synthesis of (6-((1-(4-aminophenyl)-1H-1,2,3-triazol-4-yl)methoxy)substituted benzofuran-2-yl)(phenyl)methanones, evaluation of in vitro anticancer, antimicrobial activities and molecular docking on COVID-19

A series of 4-Aminophenyl-1H 1,2,3-traizole based benzofuran analogs were synthesized with high yields straightforwardly via microwave irradiation methods than conventional methods. The structures of synthesized compounds were confirmed based on IR, 1H, 13C NMR, and HR mass spectral analysis. All the synthesized compounds were subjected to evaluation of their in vitro anticancer activity with MCF-7, PC-3, and HeLa cell lines by MTT assay, and compounds 7m, 7j, 7e, 7g, 7b, 7h, and 7c have shown good results compared to standard Doxorubicin. Further, in vitro antimicrobial activity of synthesized compounds examined by Agar Disc Diffusion method by taking gram-positive, gram-negative bacterial, and fungal strains and turned out with encouraging results compared to standard Ciprofloxacin and Fluconazole respectively. Furthermore, molecular docking studies were carried out to find out H-bonding interactions, hydrophobic interaction with docking scores of synthesized compounds. We have carried out molecular docking on COVID-19 study with COVID-19 main protease enzyme and got outstanding binding interactions.

Exploration of plant-derived natural polyphenols toward COVID-19 main protease inhibitors: DFT, molecular docking approach, and molecular dynamics simulations.

Recent outbreaks of coronavirus have brought serious challenges to public health around the world, and it is essential to find effective treatments. In this study, the 3C-like proteinase (3CLpro) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been considered as an important drug target because of its role in viral replication. We initially optimized 251 compounds at the PM7 level of theory for docking with 3CLpro, and then we selected the top 12 compounds for further optimization with the B3LYP-D3/6-311G** method and obtained the top four compounds by further molecular docking. Quantum chemistry calculations were performed to predict molecular properties, such as the electrostatic potential and some CDFT descriptors. We also performed molecular dynamics simulations and free energy calculations to determine the relative stability of the selected four potential compounds. We have identified key residues controlling the 3CLpro/ligand binding from per-residue based decomposition of the binding free energy. Convincingly, the comprehensive results support the conclusion that the compounds have the potential to become a candidate for anti-coronavirus treatment.

Pulmonary Phospholipid Components as Promising Natural Inhibitors against COVID-19 Mpro; Molecular Docking Analysis Based Study

The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome SARS-CoV-2 has become a global crisis. Phospholipids are structural components of mammalian cell membranes that suppress viral attachment to the plasma membrane and subsequent replication in lung cells. Using the molecular docking approach, the inhibitory activity of phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, lysobisphosphatidic acid and sphingomyelin against SARS CoV-2 by targeting main protease (Mpro, PDB code: 6LU7) has been investigated. All phospholipids established excellent binding to Mpro active bocket by forming several H-bonds with the catalytic amino acids Cys145 and His4, as well as various amino acids involved in the bocket. Furthermore, a potent binding affinity is increased from -7.01 to -9.16 kcal/mol compared to compound N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl- L (where L = valyl-N-1-(1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2- enyl)-L-leucinamide), a peptide linker, inhibitor for Covid-19 main protease. Co-crystalline ligand of enzyme 6LU7 of -9.99 kcal/mol. The sphingomyelin has the same binding affinity to main protease when compared to compound N3. These findings implied that the selected compounds have the potential to be developed as novel SARS-CoV-2 inhibitors. Therefore, improved, well-designed, potent and structurally and pharmacokinetically effective drugs are urgently needed. Further investigations should focus on validating and finalizing effective drugs for COVID-19 beyond preliminary in silico and in vivo screening.

Naphthoquinones from Onosma: Molecular Mechanisms of Action in the Treatment and Prevention of COVID-19

Absrtact COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in December 2019 in Wuhan, China. There is currently no effective treatment or immunization for the virus, and it is spreading rapidly with a high mortality rate. As a crucial CoV enzyme involved in initiating both viral replication and transcription, the COVID-19 main protease (Mpro) is an appealing target for researchers. Novel therapeutics are urgently required to treat the early stages of COVID-19 caused by SARS-CoV-2. Therefore, to find potential COVID-19 Mpro inhibitors, naphthoquinones from the Onosma genus were screened to find out their possible effects on the Mpro enzyme. In this study, we employed a range of computational approaches, including molecular docking and MM-GBSA, to uncover potential inhibitors of SARS-CoV-2 Mpro from existing natural product databases. According to our findings, the molecules deoxyshikonin, 3-hydroxy-isovalerylshikonin, propionylshikonin, and acetylshikonin have high binding affinities for the Mpro enzyme. In addition, it was observed that the other shikonin compounds have anti-Mpro enzyme activity. Docking simulations and molecular mechanics suggest that shikonin derivatives might be effective anti-SARS-CoV-2 compounds.

A Dispersion Corrected DFT Investigation of the Inclusion Complexation of Dexamethasone with β-Cyclodextrin and Molecular Docking Study of Its Potential Activity against COVID-19.

The encapsulation mode of dexamethasone (Dex) into the cavity of β-cyclodextrin (β-CD), as well as its potential as an inhibitor of the COVID-19 main protease, were investigated using density functional theory with the recent dispersion corrections D4 and molecular docking calculations. Independent gradient model and natural bond orbital approaches allowed for the characterization of the host–guest interactions in the studied systems. Structural and energetic computation results revealed that hydrogen bonds and van der Waals interactions played significant roles in the stabilization of the formed Dex@β-CD complex. The complexation energy significantly decreased from −179.50 kJ/mol in the gas phase to −74.14 kJ/mol in the aqueous phase. A molecular docking study was performed to investigate the inhibitory activity of dexamethasone against the COVID-19 target protein (PDB ID: 6LU7). The dexamethasone showed potential therapeutic activity as a SARS CoV-2 main protease inhibitor due to its strong binding to the active sites of the protein target, with predicted free energy of binding values of −29.97 and −32.19 kJ/mol as calculated from AutoDock4 and AutoDock Vina, respectively. This study was intended to explore the potential use of the Dex@β-CD complex in drug delivery to enhance dexamethasone dissolution, thus improving its bioavailability and reducing its side effects.

Synthesis and Identification of Novel Potential Thiadiazole Based Molecules Containing 1,2,3-triazole Moiety Against COVID-19 Main Protease Through Structure-Guided Virtual Screening Approach

In the present study, 1-(5-Methyl-1-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-1H-1,2,3-triazol-4-yl) ethan-1-one 2 was used as predecessor molecule for synthesis of methyl 2-(1-(5-methyl-1-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-1H-1,2,3-triazol-4-yl) ethylidene) hydrazine-1-carbodithioate 3. The latter compound was utilized to synthesize two new 1,3,4-thiadiazole-1,2,3-triazole hybrids 6 and 7 via its reaction with the appropriate hydrazonoyl halide derivatives 4 and 5. All the newly prepared derivatives' chemical composition was inferred from microanalytical and spectral data (FT-IR, Mass spectrometry, 1H-NMR, and 13C-NMR). Coronavirus disease (COVID-19) is an infectious disease that can cause respiratory tract infections of humans and vertebrate animals. Herein, we reported a structure-aided in silico virtual screening to identify their antiviral activity against Coronavirus through inhibition of main coronavirus protease, which plays an essential role in propagating the disease. The newly synthesized compounds showed good docking scores to COVID-19 main protease.

Molybdenum Carbonyl Complexes with Benzimidazole Derivatives Against SARS-CoV-2 by Molecular Docking and DFT/TDDFT Methods

Benzimidazole derivative molecules attract attention of scientists due to their bioactivities. The dramatic changes in recorded activities according to the type and position of the substituents motivate synthesis and analysis of new molecules. Commercial benzimidazole-based molecules have been used in therapeutic procedures. It is known that the activities of metal complexes with benzimidazole derivative ligands have different activities when compared to the benzimidazole main structure. Nowadays, one of the most important health problems is COVID-19, which caused the pandemic that we are still experiencing. Although vaccine studies are important to overcome acute problems, regarding the possible post-vaccination adverse effects, the need for new drugs against the virus is obvious. Considering the urgency and the limited facilities during the pandemic, preliminary in silico studies of candidate molecules are essential. In this study, {[bis-(N-benzylbenzimidazole)] tetracarbonylmolybdenum}, {[bis-(N-4-chlorobenzylbenzimidazole)] tetracarbonylmolybdenum} and {[bis-(N-4-methoxybenzylbenzimidazole)] tetracarbonylmolybdenum} were synthesized and characterized. The optimization and the structural analysis of these molecules were performed by DFT/TDDFT methods. The molecules were docked into SARS coronavirus main peptidase (PDB ID: 2gtb), COVID-19 main protease in complex with Z219104216 (PDB ID: 5r82), COVID-19 main protease in complex with an inhibitor N3 (PDB ID: 6lu7) and Papain-like protease of SARS-CoV-2 (PDB ID: 6w9c) crystal structures for evaluation of their anti-viral activity.

Some Novel [6-(Isoxazol-5-ylmethoxy)-3-methylbenzofuran-2-yl]phenylmethanone Derivatives, Their Antimicrobial Activity, and Molecular Docking Studies on COVID-19

A novel series of benzofuran-isoxazole hybrid heterocyclic unit has been synthesized and their structures characterized by 1H and 13C NMR, and mass spectral data. The synthesized products have been evaluated for their in vitro antibacterial and antifungal activity using Gentamycin sulphate and Nystatin as standard drugs, respectively. Four synthesized products have been determined as highly active against all tested bacterial and fungal strains. Structure–antimicrobial activity relationship has been supported by docking studies of the active compounds against glucosamine-6-phosphate synthase and aspartic proteinase. According to the docking studies, all derivatives exhibit good theoretical affinity with Autodock 4.2 software score in the range of –9.37 and –11.63 kcal/mol against the main protease of COVID-19.

Seven Compounds from Turmeric Essential Oil Inhibit Three Key Proteins Involved in SARS-CoV-2 Cell Entry and Replication in silico

Introduction: Turmeric rhizome (Cucurma longa L.) has showed great potential as a traditional drug in folk medicine of several countries. In light of the prominent use of turmeric rhizome in treating both respiratory and viral diseases, we aimed to dock major compounds from the essential oil of turmeric against three key proteins involved in COVID-19 cell entry and replication. Methods: The essential oil of turmeric rhizome was obtained using a hydrodistillation technique, and the chemical characterization of the oil was investigated using GC-MS/GC-FID. Then, main compounds were docked with the key proteins of COVID-19. Results: A total of 26 components were identified in the essential oil extracted from the rhizomes via GC-MS/GC-FID. Seven dominant compounds (turmerone (31.4%), ar-turmerone (16.1%), turmerol (14.6%), terpinolene (11.0%), [Formula: see text]-zingiberene (5.2%), [Formula: see text]-sesquiphellandrene (4.8%), and [Formula: see text]-caryophyllene (3.5%)) were docked against COVID-19 main protease, papain-like protease (PLpro), spike protein and 3C-like protease (3CLpro), and the best inhibitor was picked according to the calculated binding affinity and non-bonding interactions with the protein active site. [Formula: see text]-sesquiphellandrene and [Formula: see text]-zingiberene showed highest besides the same binding affinity towards COVID-19 virus ([Formula: see text] and [Formula: see text][Formula: see text]kcal/mol, respectively). [Formula: see text]-zingiberene was found to bind at the active site of the COVID-19 protein and interacted with different non-bonding interactions, while turmerol showed the highest affinity ([Formula: see text][Formula: see text]kcal/mol) against CLpro enzyme by binding with Met165, Leu141, Met49, Ser144, Cys145, and Glu166 residues. Conclusion: The essential oil of turmeric harbors a blend of potentially bioactive compounds that may be considered as a good target against COVID-19 virus and warrants further experimental studies.

One-pot synthesis, Spectral, X-ray crystal structure, Hirshfeld surface and computational study on potential inhibitory action of novel 1-benzyl-2-(4-methoxynaphthalen-1-yl)-4,5-diphenyl-1H-imidazole derivatives against COVID-19 main protease (Mpro: 6WCF/6Y84)

A novel compound of 1-benzyl-2-(4-methoxynaphthalen-1-yl)-4,5-diphenyl-1H-imidazole (BMNDPI) are conveniently synthesized and characterized by spectral analysis FT-IR, 1H NMR, 13C NMR, Mass spectral and density functional theory (DFT/B3LYP/6–31 G (d, p) computations. The compound BMNDPI was also confirmed by single crystal XRD. The calculated geometric parameters are consistent with XRD data. To explore the intermolecular interactions, the generated Hirshfeld surface has been investigated along with 2D-fingerprint plots. The NBO results reflect the charge transfer is mainly by the orbital overlap between n (LPN54/LPO56) and σ * C1-N55/C43-C48 bond orbital which results intra-molecular charge transfer (ICT) causing stabilization of the system. Stability and charge transfer within the compound was explained by frontier molecular orbital calculations. Atomic charges on the various atoms of BMNDPI obtained by Mulliken population analysis. Potential reactive sites of the BMNDPI compound have been identified by MEP which is mapped to the electron density surfaces. The reported molecule is used as a potential NLO material since it has a high μβ0 value. The molecular docking mechanism between BMNDPI ligand and COVID-19/6WCF and COVID-19/6Y84 receptors were studied to investigate the binding modes of these compounds at the active sites. Molecular docking outcomes have shown that the BMNDPI molecule can be considered as a potential agent against COVID-19/6WCF-6Y84 receptors.

Design of new bis-triazolyl structure for identification of inhibitory activity on COVID-19 main protease by molecular docking approach

In the rapidly growing COVID-19 pandemic, designing of new drugs and evaluating their inhibitory action against main targets of corona virus could be an effective strategy to accelerate the drug discovery process and their efficacy towards corona virus disease. Herein, we design new bis-triazolyl probe for an investigation of inhibitory activity towards COVID-19 main protease by Molecular docking approach. The formulated compound has been thoroughly characterized by elemental analysis, NMR (1H and 13C) and complete structure elucidation was achieved via X-ray crystallography. Docking study reveals that newly synthesized compound confers good inhibitory response to COVID-19 main protease as supported by calculated docking score and binding energy. Strong hydrogen bonding and hydrophobic interactions of the newly synthesized compound with several important amino acids of the main protease also helps to explain the potency of the compound to inhibit the main protease. We hope that the present study would help the researcher in the field of Medicinal chemistry and to develop potential drug against the novel corona virus.

A Combined Molecular Docking and Density Functional Theory Nuclear Magnetic Resonance Study of Trans-Dehydrocrotonin Interacting with COVID-19 Main Protease and Severe Acute Respiratory Syndrome Coronavirus 2 3C-Like Protease

For the development of drugs that treat SARS-CoV-2, the fastest way is to find potential molecules from drugs already on the market. Unfortunately, there is currently no specific drug or treatment for COVID-19. Among all structural proteins in SARS-CoV, the spike protein is the main antigenic component responsible for inducing host immune responses, neutralizing antibodies, and/or protecting immunity against virus infection. Molecular docking is a technique used to predict whether a molecule will bind to another. It is usually a protein to another or a protein to a binding compound. Natural products are potential binders in several studies involving coronavirus. The structure of the ligand plays a fundamental role in its biological properties. The nuclear magnetic resonance technique is one of the most powerful tools for the structural determination of ligands from the origin of natural products. Nowadays, molecular modeling is an important accessory tool to experimentally got nuclear magnetic resonance data. In the present work, molecular docking studies aimed is to investigate the limiting affinities of trans-dehydrocrotonin molecule and to identify the main amino acid residues that could play a fundamental role in their mechanism of action of the SARS-CoV spike protein. Another aim of this work is all about to evaluate 10 hybrid functionalities, along with three base pairs using computational programs to discover which ones are more reliable with the experimental result the best computational method to study organic compounds. We compared the results between the mean absolute deviation (MAD) and root-mean-square deviation (RMSD) of the molecules, and the smallest number between them was the best result. The positions assumed by the ligands in the active site of the spike glycoprotein allow assuming associations with different local amino acids.

Computational screening of natural compounds from Salvia plebeia R. Br. for inhibition of SARS-CoV-2 main protease.

The novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has emerged to be the reason behind the COVID-19 pandemic. It was discovered in Wuhan, China and then began spreading around the world, impacting the health of millions. Efforts for treatment have been hampered as there are no antiviral drugs that are effective against this virus. In the present study, we have explored the phytochemical constituents of Salvia plebeia R. Br., in terms of its binding affinity by targeting COVID-19 main protease (Mpro) using computational analysis. Molecular docking analysis was performed using PyRx software. The ADMET and drug-likeness properties of the top 10 compounds showing binding affinity greater than or equal to − 8.0 kcal/mol were analysed using pkCSM and DruLiTo, respectively. Based on the docking studies, it was confirmed that Rutin and Plebeiosides B were the most potent inhibitors of the main protease of SARS-CoV-2 with the best binding affinities of − 9.1 kcal/mol and − 8.9 kcal/mol, respectively. Further, the two compounds were analysed by studying their biological activity using the PASS webserver. Molecular dynamics simulation analysis was performed for the selected protein–ligand complexes to confirm their stability at 300 ns. MM-PBSA provided the basis for analyzing the affinity of the phytochemicals towards Mpro by calculating the binding energy, and secondary structure analysis indicated the stability of protease structure when it is bound to Rutin and Plebeiosides B. Altogether, the study identifies Rutin and Plebeiosides B to be potent Mpro inhibitors of SARS-CoV-2.Graphic abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s42535-021-00304-z.

Repurposing drug molecule against SARS-Cov-2 (COVID-19) through molecular docking and dynamics: a quick approach to pick FDA-approved drugs.

A novel coronavirus known as severe acute respiratory syndrome is rapidly spreading worldwide. The international health authorities are putting all their efforts on quick diagnosis and placing the patients in quarantine. Although different vaccines have come for quick use as prophylactics, drug repurposing seems to be of paramount importance because of inefficient therapeutic options and clinical trial limitations. Here, we used structure-based drug designing approach to find and check the efficacy of the possible drug that can inhibit coronavirus main protease which is involved in polypeptide processing to functional protein. We performed virtual screening, molecular docking and molecular dynamics simulations of the FDA-approved drugs against the main protease of SARS-CoV-2. Using well-defined computational methods, we identified amprenavir, cefoperazone, riboflavin, diosmin, nadide and troxerutin approved for human therapeutic uses, as COVID-19 main protease inhibitors. These drugs bind to the SARS-CoV-2 main protease conserved residues of substrate-binding pocket and formed a remarkable number of non-covalent interactions. We have found diosmin as an inhibitor which binds covalently to the COVID-19 main protease. This study provides enough evidences for therapeutic use of these drugs in controlling COVID-19 after experimental validation and clinical demonstration.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00894-021-04923-w.

Molecular docking identification of plant-derived inhibitors of the COVID-19 main protease

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.

Repositioning of Fungal-based Peptides as Modulators of Angiotensin-converting Enzyme-related Carboxypeptidase, SARS-coronavirus HR2 Domain, and Coronavirus Disease 2019 Main Protease.

Background and ObjectivesAngiotensin-converting enzyme-related carboxypeptidase, SARS-Coronavirus HR2 Domain, and COVID-19 main protease are essential for the cellular entry and replication of coronavirus in the host. This study investigated the putative inhibitory action of peptides form medicinal mushrooms, namely Pseudoplectania nigrella, Russula paludosa, and Clitocybe sinopica, towards selected proteins through computational studies.Materials and MethodsThe respective physicochemical properties of selected peptides were predicted using ProtParam tool, while the binding modes and binding free energy of selected peptides toward proteins were computed through HawkDock server. The structural flexibility and stability of docked protein–peptide complexes were assessed through iMODS server.ResultsThe peptides showed an optimum binding afinity with the molecular targets; plectasin from P. nigrella showed the highest binding free energy compared to peptides from R. paludosa and C. sinopica. Besides, molecular dynamic simulations showed all fungal-based peptides could influence the flexibility and stability of selected proteins.ConclusionThe study revealed fungal-based peptides could be explored as functional modulators of essential proteins that are involved in the cellular entry of coronavirus.