|
| Author | Year | Method | Detail of method | Name of compound/drug | Target | Efficacy | Comments |
|
| Abu-Melha et al. [211] | 2020 | In silico | Molecular docking combined with molecular dynamic simulation (MDS) | Hydrazones, pyrazoles, and pyrazines bearing thiazole moiety | Main protease | The average binding affinities of the compounds 3a, 3b, and 3c (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control nelfinavir | |
| Aghaee et al. [212] | 2021 | In silico | Pharmacophore model molecular docking combined with molecular dynamic simulation (MDS), MM/PBSA, ADME studies | Pharmit website | Main protease | ML188, nelfinavir, lopinavir, ritonavir, and α-ketoamide | |
| Ahmad et al. [213] | 2021 | In silico | Structure-based virtual screening (SBVS) of ASINEX antiviral library, molecular dynamic (MD) simulations | ASINEX antiviral library | Main protease | SCHEMBL12616233, SCHEMBL18616095, and SCHEMBL20148701 compounds conformation with main protease show good stability after initial within active cavity moves, a rich intermolecular network of chemical interactions, and reliable relative and absolute binding free energies | BBB_26580140 lead and its similar analogs to be explored in vivo lead molecules |
| Ahmed et al. [214] | 2020 | In silico | Molecular docking, molecular dynamics, and structure-activity relationship | 76 prescription antiviral drugs | RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) | Raltegravir, simeprevir, cobicistat, and daclatasvir have higher binding energy and strong interaction with active sites of the receptor proteins (with a precision of 85%) | |
| Alabboud and Javadmanesh [215] | 2020 | In silico | Molecular docking combined with molecular dynamic simulation | 88 conventional drugs, 16 vitamins, and 63 natural (plant) | Main protease | Various vitamins (B9, A, K, and E vitamins) exhibited a significantly strong interaction with the studied receptor. Pleconaril, adefovir dipivoxil, and stavudine in addition to plant-based compounds such as curcumin (Curcuma longa), anolignan A (Anogeissus acuminata), and phyllamyricin B (Phyllanthus myrtifolius) had strong ligand-protein interactions | |
| Alamri et al. [216] | 2020 | In silico | Structure-based virtual screening coupled with all-atom molecular dynamic (MD) simulations | Protease inhibitors database composed of ∼7,000 compounds | Papain-like protease | ADM_13083841, LMG_15521745, and SYN_15517940 showed stable conformation and interacted well with the active residues of papain-like protease | |
| Alexpandi et al. [217] | 2020 | In silico | Molecular docking | 113 quinoline drugs | Main protease, RNA-dependent RNA polymerase (RdRp) inhibitors spike-RBD-ACE2 inhibitor | Elvitegravir and oxolinic acid are able to interact with the NTP entry channel and thus interfere with the RNA-directed 5′–3′ polymerase activity of SARS-CoV-2 RdRp. Rilapladib is the only quinoline that can interrupt the spike-RBD-ACE2 complex | Quinoline, 1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI), saquinavir, elvitegravir, oxolinic acid, and rilapladib are suggested for the treatment of COVID-19 |
| Al‐Sehemi et al. [218] | 2020 | In silico | Molecular docking, MD simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) results | Phenyl furoxan, an exogenous nitric oxide donor | Main protease | Spiro-isoquinolino-piperidine-furoxan moieties can be used as an effective ligand for main protease inhibition due to the presence of key isoquinolino-piperidine skeleton with additional NO effect | |
| Al-Shar’i [219] | 2020 | In silico | Molecular docking, MD simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) results | Different databases | Main protease | 9 compounds with different chemotypes | |
| Badavath et al. [220] | 2020 | In silico/in vitro | Molecular docking, molecular dynamics, and structure-activity relationship studies | Screening of 118 compounds with 16 distinct heterocyclic moieties in comparison with 5 natural products and 7 repurposed drugs | Main protease | Oxidiazoles (A2 and A4) derivatives have the best docking scores. Structure-activity relationship studies showed a good comparison with a known active main protease and repurposed drug ebselen with an IC50 value of −0.67 μM | |
| Barros et al. [221] | 2020 | In silico | Molecular docking | 24 ligands | SARS-CoV-2 receptors, Nsp9 replicase, main protease (Mpro), NSP15 endoribonuclease, and spike protein (S protein) interacting with human ACE2 | Antimalarial drug metaquine and anti-HIV antiretroviral saquinavir interacted with all the studied receptors | |
| Basit et al. [222] | 2020 | In silico | Protein-protein docking and molecular dynamic simulation | Truncated version of human ACE2 (tACE2) | S Glycoprotein | tACE2 provides a high-affinity protein inhibitor for S glycoprotein | |
| Battisti et al. [223] | 2020 | In silico | Pharmacophore‐based screening, docking consensus approach (DCA), molecular dynamic simulations, common hit approach (CHA) | Aldrich Market Select (AMS) database from ChemNavigator/Sigma‐Aldrich with over 8 million unique chemical structures | Against SARS-CoV-2 | 10 compounds with high coronavirus inhibition potential | Lead molecules |
| Benítez-Cardoza and Vique-Sánchez [224] | 2020 | In silico | Molecular docking | 500,000 compounds | Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD) | 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD | |
| Cava et al. [225] | 2020 | In silico | Gene Ontology and enrichment analysis protein-protein interaction (PPI) network virtual screening method | — | Against SARS-CoV-2 | A protein-protein interaction network of 193 genes, 22 interactions, and 36 potential drugs for future treatment strategies including nimesulide, fluticasone propionate, thiabendazole, photofrin, and didanosine | Only didanosine is a real antiviral drug, while the others are mostly anti-inflammatory |
| Chen et al. [226] | 2020 | In silico | Crystal structure, virtual screening | 7173 purchasable drugs (drugs-lib), with 4574 unique compounds and their stereoisomers | Main protease | 16 candidates for consideration, ledipasvir velpatasvir | |
| Choudhary et al. [227] | 2020 | In silico | Molecular docking, MM-GBSA predictive binding energy calculations, and molecular dynamic simulation | 15,754 natural and synthetic compounds | Main protease | Compound 2 (molecular bank code AAA396) and compound 3 (molecular bank code AAD146) | |
| Chunduru et al. [228] | 2021 | In silico | Molecular docking | Novel drug-like inhibitors for COVID-19 | Main protease | Structure 61 was found to be more stable and can be further assessed for their antiviral activity to combat COVID-19 | |
| Coelho et al. [229] | 2020 | In silico | Biochemical high-throughput screening | Compound library containing known drugs, bioactive molecules, and natural products | Main protease | Organomercuric compounds thimerosal and phenylmercuric acetate, benzophenone, Evans blue, a sulfonic acid-containing dye | |
| Dai et al. [230] | 2020 | In silico | Structure-based design | — | Main protease | Designed and synthesized two lead compounds (11a and 11b) targeting main protease. Both exhibited excellent inhibitory activity | |
| de lima Menezes and da Silva [231] | 2020 | In silico | Molecular dynamic simulations, molecular docking | DrugBank database | Nonstructural protein 1 (nsp1) | Tirilazad, phthalocyanine, and Zk-806450 showed better energy score than control molecules that have in vitro activity against nsp1 from SARS-CoV-2 | Tirilazad, phthalocyanine, and Zk-806450 |
| Debnath et al. [232] | 2020 | In silico | Pharmacophores studies, structure-based virtual screening, molecular dynamic (MD) simulation | Drug molecule information retrieved from DrugBank | Main protease | DB07456 and DB13592 displayed a similar type of binding interaction with co-ligands and remdesivir, and the predicted Ki values of 2 inhibitors were found to be superior to remdesivir | |
| Di Micco et al. [233] | 2021 | In silico | Molecular docking, MM-GBSA-based predictions, and molecular dynamics | Zonulin inhibitor larazotide acetate (also called AT1001) | Main protease | AT1001, besides its well-demonstrated effect in ameliorating mucosal permeability in ALI/ARDS | |
| El Hassab et al. [234] | 2021 | In silico | Structure-based virtual screening, molecular dynamic simulation, and MM-PBSA approaches | 48 million drug-like compounds of the ZINC database | SARS-CoV-2 2′-O-methyltransferase (nsp16) | Compound 11 as the best potential nsp16 inhibitor herein identified, as it displayed a better stability and average binding free energy for the ligand-enzyme complex compared to sinefungin | |
| Elmessaoudi-Idrissi et al. [235] | 2020 | In silico | In silico screening, molecular docking, and dynamic approaches | 5000 compounds of the ZINC database | Main protease | The prominent drug-like and potent inhibitory compounds are 2-[2-(2-aminoacetyl) aminoacetyl] amino-3-(4-hydroxyphenyl)-propanamide (ZINC000004762511), 6′-fluoroaristeromycin (ZINC000001483267), and cyclo(L-histidyl-L-histidyl) (ZINC000005116916) scaffolds | |
| Feitosa et al. [236] | 2020 | In silico | Molecular docking | — | Main protease | Melatonin can have response potential in early stages for its possible effects on ACE2 and main protease, although it is also promising in more severe stages of the disease for its action against hyper-inflammation | Do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials |
| Gurung et al. [237] | 2021 | In silico | Virtual screening, molecular docking | 1,36,191 molecules | Spike (S) protein receptor-binding domain (RBD) to the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2) | ZINC33039472 exhibited binding free energy value lower as compared to the control (emodin) with a higher contribution by gas-phase energy and van der Waals energy to the total binding free energy | |
| Haider et al. [238] | 2020 | In silico | Computer-aided drug design (CADD) molecular docking | ZINCPharmer | Main protease | ∼200 compounds were identified as having strong interaction with Mpro (ZINC20291569, ZINC90403206, ZINC95480156) that showed the highest binding energy | |
| Hall and Ji [239] | 2020 | In silico | Homology modeling molecular docking | ZINC15 database: 3447 entries | Spike glycoprotein and main protease | Zanamivir, indinavir, saquinavir, and remdesivir are among the exciting hits of main proteinase | Flavin adenine dinucleotide (FAD) adeflavin, B2 deficiency medicine, and coenzyme A, a coenzyme may also be potentially used for the treatment of SARS-CoV-2 infections |
| Havranek and Islam [240] | 2020 | In silico | Docking and molecular dynamics | 2692 protease inhibitor compounds | Main protease | Phenyltriazolinones (PubChem ID: 104161460) and allosteric HCV NS5B polymerase thumb pocket 2 (PubChem ID: 163632044) have shown antiviral activity and also have high affinity towards the main protease | |
| Ibrahim et al. [241] | 2021 | In silico | Molecular dynamic simulations, molecular docking, MM-GBSA | 18 anti-COVID-19 drug candidates against SARS-CoV-2 main protease | Main protease | Promising binding affinities of TMC-310911 and ritonavir | |
| Jaiswal and Kumar [242] | 2020 | In silico | Docking studies and molecular dynamic simulation | Designed a protein inhibitor | Spike (S) glycoprotein | The proposed inhibitor ΔABP-D25Y | |
| Jamalan et al. [243] | 2021 | In silico | Docking and molecular dynamic (MD) simulation | Virtual screening based on GRL-0617 | Papain-like proteinase | 5-(aminomethyl)-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide outperformed GRL-0617 in terms of binding affinity (−9.7 kcal/mol). 2-(4-fluorobenzyl)-5-nitro-1H-isoindole-1,3(2H)-dione, 3-nitro-N-[(1r)-1-phenylethyl]-5-(trifluoromethyl)benzamide, 5-acetamido-2-methyl-N-[(1S)-1-naphthalen-1-ylethyl]benzamide | |
| Jin et al. [244] | 2020 | In silico | Structure-assisted drug design, virtual drug screening, and high-throughput screening | 10,000 compounds | Main protease | Ebselen, disulfiram, tideglusib, carmofur, shikonin, PX-12 | Ebselen also exhibited promising antiviral activity in cell-based assays |
| Kanhed et al. [245] | 2021 | In silico | Systematic virtual screening approach | ASINEX BioDesign library approved drug library | Main protease | Ritonavir, nelfinavir, and saquinavir were predicted to be the most potent Mpro inhibitors. 20 molecules (pyrazoles, cyclic amides, pyrrolidine-based compounds, and miscellaneous derivatives) | |
| Kavitha et al. [246] | 2020 | In silico | Molecular docking molecular dynamic simulations | 1000 protease-inhibitor-like compounds available in the ZINC database | Main protease | 1,2,4 triazolo[1,5-a] pyrimidin-7-ones | |
| Krishnan et al. [247] | 2020 | In silico | Molecular docking | 3978 compounds with potential antiviral activity | Endoribonuclease (NSP15) | 8 compounds with good docking score and docking energy e.g., Z595015370, Z1343129850, and Z2760938911 | |
| Kumar et al. [248] | 2021 | In silico | Molecular docking molecular dynamic simulation molecular mechanic Poisson–Boltzmann surface area approaches | Million molecules and natural compound databases | Main protease | Three compounds namely ZINC14732869, ZINC19774413, and ZINC19774479 displayed better binding affinities | |
| Kumar et al. [249] | 2020 | In silico | Molecular docking molecular dynamic simulations | 13 approved antiviral drugs | Main protease | Indinavir was described as a lead drug. Indinavir possesses an important pharmacophore | Novel compound 16(hydroxyethylamine derivative) suitability as a strong candidate for therapeutic discovery against COVID-19 |
| Kwarteng et al. [250] | 2020 | In silico | Bioinformatic approach molecular docking molecular dynamic simulations | — | Nucleocapsid (N) protein | Zidovudine triphosphate, an anti-HIV agent, as a potential inhibitor of the N-terminal domain of SARS-CoV2 N protein | |
| Li et al. [251] | 2021 | In silico | Molecular docking | 21 antiviral, antifungal, and anticancer compounds | Papain-like protease | Neobavaisoflavone | |
| Mathpal et al. [252] | 2020 | In silico | Molecular docking molecular dynamic simulation MM-PBSA | 3180 FDA-approved drugs from “the ZINC database” | Main protease | ZINC03831201, ZINC08101052, ZINC01482077, and ZINC03830817 | |
| Maurya et al. [253] | 2020 | In silico | Molecular docking | Antiviral, anti-infectious, and anti-protease compounds | NSP10/NSP16 methyltransferase and main protease | Cyclocytidine hydrochloride, trifluridine adonitol, and meropenem penciclovir bound with a good docking score NSP10/NSP16 methyltransferase complexed with telbivudine, oxytetracycline dihydrate, methyl gallate, 2-deoxyglucose, and daphnetin | |
| Mohamed et al. [254] | 2020 | In silico | Molecular docking | 12 histone deacetylases (HDACs) | Main protease | Romidepsin and its active form (RedFK) | |
| Monajemi and Zain [255] | 2021 | In silico | ONIOM (own N-layered integrated molecular orbital and molecular mechanics; QM/MM) approach | N3, ebselen, disulfiram, tideglusib, carmofur, shikonin, and PX-12 | Main protease | N3, ebselen, and PX-12 inhibitors | Better inhibition from PX-12 than ebselen |
| Motiwale et al. [256] | 2020 | In silico | Molecular docking molecular dynamic simulations | Previously reported SARS-3CL protease inhibitors | Main protease | N-substituted isatin derivatives and pyrazolone | |
| Mutlu et al. [257] | 2020 | In silico | Structure-based approach molecular docking molecular dynamic simulations | FDA-approved and investigational drugs | Nsp12/Nsp8 | Two drugs, RX-3117 (fluorocyclopentenyl cytosine) and nebivolol | |
| Naidoo et al. [258] | 2020 | In silico | Molecular docking molecular dynamic simulation MM-PBSA | Cyanobacterial metabolites | Main protease (Mpro) and the papain-like protease (PLpro) | Deoxycylin, drospermopsin | Cylindrospermopsin, deoxycylindrospermopsin, carrageenan, cryptophycin 52, eucapsitrione, tjipanazole, tolyporphin, and apratoxin A exhibited promising inhibitory potential against the SARS-CoV-2 Mpro. The compounds cryptophycin 1, cryptophycin 52, and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PLpro of SARS-CoV-2 |
| Olubiy et al. [259] | 2020 | In silico | Molecular docking molecular dynamic simulations | Approved drugs, investigational drugs, natural products, and organic compounds | Main protease | Several tyrosine kinase inhibitors, which include a bioflavonoid and steroid hormones, bind best to main protease | Nilotinib, enasidenib, afatinib, ertapenem, phthalocyanine, hypericin, amrubicin, theacitrin A, theaflavin, amentoflavone, epigallocatechin gallate, glabrolide, cortisol, estradiol, testosterone |
| Özdemir et al. [260] | 2020 | In silico | Molecular docking density functional theory (DFT) ADME-Tox | 42 coumarin derivatives | Main protease | 6,7-Dihydroxy-3-phenylcoumarin derivatives gave relatively higher scores, and for all coumarins, and 4-trifluoromethylphenyl substituted coumarin had the highest score | |
| Ozdemir et al. [261] | 2020 | In silico | Molecular docking molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) | Coumarin derivatives | Spike S1 subunit, NSP5, NSP12, NSP15, and NSP16 | The highest score (−10.01 kcal/mol) in the coumarin group is 2-morpholinoethan-1-amine substituted coumarin | |
| Patel et al. [262] | 2021 | In silico | Pharmacophore studies | Drug library (having drugs and diagnostic agents, which are approved by FDA or other world authorities) and the ASINEX BioDesign library | Main protease | Ritonavir, nelfinavir, and saquinavir were predicted to be the most potent Mpro inhibitors 20 molecules categorized into four classes viz. disubstituted pyrazoles, cyclic amides, pyrrolidine-based compounds, and miscellaneous derivatives | |
| Peng et al. [263] | 2020 | In silico | Drug repositioning through virus-drug association prediction | — | Against SARS-CoV-2 | Ribavirin was predicted to be the best small molecular drug, with a higher molecular binding energy with human angiotensin-converting enzyme 2 (ACE2), followed by remdesivir, mycophenolic acid, and chloroquine (−6.29 kcal/mol) | |
| Pratama et al. [264] | 2020 | In silico | Molecular docking | Novel 5-O-benzoylpinostrobin derivatives | Main protease | Three 5-O-benzoylpinostrobin derivatives each with fluoro, tertiary butyl, and trifluoromethyl substituents at 4-position of benzoyl group showed the lowest free energy of binding value and the highest similarity of ligand-receptor interactions with co-crystallized ligands | |
| Pundir et al. [265] | 2020 | In silico | Pharmacophore-based virtual screening molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) | PubChem database | Main protease | Two compounds: PubChem3408741 and PubChem4167619 had the binding free energy of −94.02 kJ·mol−1 and −122.75 kJ·mol−1, respectively, as compared to reference X77 (−76.48 kJ·mol−1) | Lead molecules for targeting Mpro enzyme |
| Quimque et al. [266] | 2020 | In silico | Molecular docking molecular dynamic simulation ADME properties | 97 antiviral secondary metabolites from fungi | Papain-like protease, RNA-dependent RNA polymerase, main protease, spike glycoprotein, nonstructural protein 15 (nsp15) | Two fumiquinazoline alkaloids quinadoline B (19), scedapin C (15), and polyketide isochaetochromin D1 (8) | Quinadoline B [19] was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability, and poor blood-brain barrier crossing capacities |
| Rakib et al. [267] | 2021 | In silico | Molecular docking molecular dynamic simulation ADME properties | Selenium-containing heterocyclic compounds | Main protease | Selection of the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. Ethaselen showed potential binding affinities | |
| Rane et al. [268] | 2020 | In silico | Molecular docking molecular dynamic simulations | Diarylpyrimidine analogs | Spike glycoprotein | AP-NP (2-(2-amino-5-(naphthalen-2-yl)pyrimidin-4-yl)phenol), AP-3-OMe-Ph (2-(2-amino-5-(3-methoxyphenyl)pyrimidin-4-yl)phenol), and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl) pyrimidin-4-yl)phenol) from a group of diarylpyrimidine derivatives, which appears to bind at the interface of the hACE2-S complex with low binding free energy | |
| Rao et al. [269] | 2020 | In silico | Molecular docking molecular dynamic simulations | Various small molecules | Main protease | Pyranonigrin A, a secondary fungal metabolite | |
| Salman et al. [270] | 2020 | In silico | Molecular docking molecular dynamic simulation ADME properties | Library of immunomodulatory medicinal compounds with antiviral capability | SARS proteases, spike protein, and nonstructural proteins (NSP-9, 15) | 6 compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol, and thymohydroquinone | Good pharmacokinetic properties and low acute toxicity of these compounds |
| Sarma et al. [271] | 2020 | In silico | Molecular docking MM-GBSA binding free energy molecular dynamic simulations | 56,079 compounds from ASINEX and Maybridge library | RNA-binding N-terminal domain (NTD) of the N protein | ZINC00003118440 is a theophylline derivative. Pyrimidone derivatives as possible inhibitors of RNA binding to the N-terminal domain of N protein of coronavirus | Lead molecules |
| Sepay et al. [272] | 2020 | In silico | Molecular docking, bioinformatics, and molecular electrostatic potential ADME studies | Benzylidenechromanones, naturally occurring oxygen heterocyclic compounds | Main protease | (Z)-3-(4 ′-chlorobenzylidene)-thiochroman-4- | Effective pharmacological properties |
| Shehroz et al. [273] | 2020 | In silico | Pharmacophore modeling molecular docking | DrugBank, ZINC, and TIMBLE databases | Spike (S) protein | Only eight molecules fit the criteria for safe oral drugs | Lead molecules |
| Singh and Das [274] | 2021 | In silico | Molecular docking | Chloroquine (CQ) hydroxychloroquine (HCQ) azithromycin | Spike (S) protein main protease host cathepsin L (CTSL) receptor-binding domain (RBD) | Azithromycin affinity scores (ΔG) with strong interactions with ACE2, CTSL, Mpro, and RBD. CQ firm bond score with Mpro HCQ and two results (ACE2 and Mpro) were firmly bound to the receptors | |
| Stefaniu et al. [275] | 2020 | In silico | Molecular docking density functional theory (DFT) computations, drug-likeness assessment | Derivatives of benzoic acid | Main protease | 2,5-dihydroxybenzoic acid (gentisic acid) and octyl | A combination of the two compounds can be considered |
| Tachoua et al. [276] | 2020 | In silico | Molecular docking and structural dynamic study molecular mechanic Poisson–Boltzmann surface area (MM-PBSA) ADMET analysis | Chloroquine, quinine, nitazoxanide, doxycycline, lymecycline, cetirizine, mizolastine, indinavir | Main protease | Lymecycline mizolastine | |
| Uniyal et al. [277] | 2020 | In silico | Structure-based virtual screening molecular docking MM-GBSA binding free energy molecular dynamic simulations | Commercially available chemical libraries | Main protease | Compound AG-690/11203374_1 and AG-690/11203374_2 emerged as the best in silico hits based on the docking, MM-GBSA, dynamics, and ADMET studies | Lead molecules |
| Welker et al. [278] | 2020 | In silico/in vitro | Structure-activity relationships molecular docking fluorescence-based enzyme‐activity assay Vero E6 cells | A series of rationally designed competitive, noncovalent, nonpeptidic active site‐directed SARS‐CoV PLpro inhibitors | Papain-like cysteine proteases (PLpro) | R)‐5‐amino‐2‐methyl‐N‐(1‐(naphthalen‐1‐yl)ethyl) benzamide (2b), which is known to bind into the S3 and S4 pockets of the SARS‐CoV PLpro. Isoindoline as a new class of potent PLpro inhibitors | IC50 value of 2.9 ± 0.2 μM |
| Wen et al. [279] | 2021 | In silico | Structure-based screening | 8,820 compounds | Main protease | Trichostatin A | A histone deacetylase inhibitor and an antifungal compound |
| White et al. [280] | 2020 | In silico | Homology modeling and molecular dynamics approach molecular docking | ∼970,000 chemical compounds | Helicase (Nsp13) | Nilotinib and lumacaftor have significant activity in inhibiting purified recombinant SARS-CoV-2 helicase | |
| Wu et al. [281] | 2020 | In silico | Molecular docking | 11 HIV-1 protease inhibitors, 12 nucleotide-analog inhibitors, 728 approved drugs | Main protease RNA-dependent RNA polymerase | Remdesivir shows the best binding energy on RdRp and saquinavir is the best inhibitor of main protease | |
| Zaher et al. [282] | 2020 | In silico | Design, synthesis SAR study molecular docking | Newly synthesized sixteen halogenated triazole compounds | Helicase (Nsp13) | The most potent compounds were 4-(cyclopent-1-en-3-ylamino)-5-(2-(4-iodophenyl)hydrazinyl)-4H-1,2,4-triazole-3-thiol [16] and 4-(cyclopent-1-en-3-ylamino)-5-[2-(4-chlorophenyl)hydrazinyl]-4H-1,2,4-triazole-3-thiol [12] | |
| Zarezade et al. [283] | 2021 | In silico | 3D-QSAR pharmacophore modeling ADMET properties, molecular docking molecular dynamic simulation MM-PBSA, hybrid QM-MM method de novo ligand design | PubChem and ZINC databases | Human angiotensin-converting enzyme 2 and main protease | ZINC12562757 and 112,260,215 were the best potential inhibitors of the ACE2 and main protease, respectively. Evo_1 compound enjoys the highest docking energy among the designed de novo ligands | Evo_1 has a stronger potential for specific inhibition of main protease, as compared to the 112, 260, 215 compound. Lead molecules |
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