|
| Author | Year | Method | Detail of method | Name of compound/drug | Target | Efficacy | Comments |
|
| Abosheasha and El-Gowily [24] | 2020 | In silico | Drug repurposing molecular docking-based virtual screening | 15 antiplatelet FDA-approved drugs | Main protease (Mpro) and spike glycoprotein (S) | Cilostazol has favorable binding interaction with Mpro (PDB ID: 6LU7) cilostazol, iloprost, epoprostenol, prasugrel, and icosapent ethyl that have a higher binding affinity on spike glycoprotein (S) | Cilostazol is a promising FDA drug against COVID-19 by inhibiting both Mpro and S protein |
| Abdul Kadhim et al. [25] | 2020 | In silico | Drug repurposing, docking | Experimental and approved drugs | Papain-like protease and RNA polymerase | Drugs that shared >70% similarity to the binding sites of those targets were reversin, pentagastrin, remdesivir, norfloxacin, and nitazoxanide against COVID-19 papain-like protease whereas benzylglutathione, lopinavir, and hydroxymethylglutathione against RNA polymerase | Antiresistance reversin showed the highest inhibitory efficacy against COVID-19 papain-like protease, and benzylglutathione is an experimental compound; however, it had the highest RNA polymerase inhibiting efficacy |
| Abu-Saleh et al. [26] | 2020 | In silico | Ligand-based/structure-based virtual screening, MD simulations, and binding energy calculations | Approved drugs and bioactive compounds listed in the DrugBank and ChEMBL databases | Main protease | Best MM/GBSA binding energy; ChEMBL275592, montelukast, ChEMBL28834. Bromocriptine and saquinavir demonstrate stability in the active site of Mpro | |
| Achilonu et al. [27] | 2020 | In silico | High-throughput virtual screening and ligand docking | FDA-approved drugs | Main protease | Isavuconazonium, a P2-P3 α-ketoamide derivative, and pentagastrina are the top three molecules (Lig13b as the benchmark) based on docking energy | |
| Aftab et al. [28] | 2020 | In silico | Repositioning/target-based virtual screening and molecular docking | Ten antiviral drugs were screened: ribavirin, remdesivir, sofosbuvir, penciclovir, nitazoxanide, nafamostat, chloroquine, galidesivir, favipiravir, and interferon | RNA-dependent RNA polymerase (RdRp) | Galidesivir and its drug-like compounds CID123624208 and CID11687749 have shown an effective attachment to the priming site of viral RdRp | CID123624208 and CID11687749 may be considered for in vitro and in vivo clinical trials |
| Ahmadi et al. [29] | 2021 | In silico | Drug repurposing study using molecular docking | Enfuvirtide, an HIV-1 fusion inhibitor peptide | SARS-CoV-2 fusion inhibitor | Enfuvirtide binding to the S2 protein of SARS-CoV-2 was remarkably stable and can act as a strong SARS-CoV-2 fusion inhibitor | |
| Ahmed et al. [30] | 2021 | In silico | Drug repurposing (high-throughput virtual screening) (HTVS) followed by re-docking with standard precision (SP) and extra-precision (XP) molecular docking | FDA-approved antiviral and anti-infection drugs | Main protease | Of 1397 potential drugs, 157 showed considerable affinity towards Mpro. High-affinity lead drugs (iodixanol, amikacin, troxerutin, and rutin) were identified. Amikacin was found to be the most potent inhibitor of main protease | Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19 |
| Anand et al. [31] | 2021 | In silico | Molecular docking | 130 US FDA-approved drugs including hypertension, cardiovascular diseases, respiratory tract infections (RTI), antibiotics, and antiviral drugs | Structural and nonstructural proteins of SARS-CoV-2 (nsp3, nsp5, nsp10, nsp16) | 15 potent drugs exhibiting significant inhibitory potential against SARS-CoV-2 like baloxavir marboxil, danoprevir and sofosbuvir, fosinopril, moexipril, quinapril, telmisartan, azilsartan, verapamil, and doxazosin | Azithromycin, doxycycline, clarithromycin, rifamycin, and augmentin: nsp10; virginiamycin, tunicamycin, quinupristin, fidaxomicin, digoxin, and azithromycin: main protease; caspofungin, amphotericin B, ketoconazole, and micafungin: E and N proteins; virginiamycin and amphotericin B: S protein |
| Ancy et al. [32] | 2020 | In silico | Molecular docking, molecular dynamics, and binding free energy simulation study | HIV-1 protease, namely, TMB607 and TMC-310911 | Main protease | TMB607 molecule binds strongly with the SARS-CoV-2 main protease enzyme | |
| Ansari et al. [33] | 2020 | In silico | Repurposing drug molecular docking | TAT-peptide 47–57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) | Main protease | TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with main protease | |
| Arun et al. [34] | 2020 | In silico | Repurposing drug molecular docking | Drugs available in the super DRUG2 database | Main protease | Binifibrate and bamifylline bind strongly to the enzyme active site | |
| Arya et al. [35] | 2020 | In silico | Molecular docking | FDA-approved drugs | Papain-like protease | 15 FDA-approved drugs, including chloroquine and formoterol, bind the target enzyme with significant affinity and good geometry, suggesting their potential to be utilized against the virus | |
| Baby et al. [36] | 2020 | In silico | Schrodinger’s computer-aided drug discovery tools for in silico drug repurposing | FDA-approved library of drugs | RNA-dependent RNA polymerase (RdRp) | Pitavastatin, ridogrel, rosoxacin | |
| Baby et al. [36] | 2021 | In silico | Schrodinger’s computer-aided drug discovery tools for in silico drug repurposing | FDA-approved library of drugs | Main protease | Tipiracil and aprepitant interacted with the main protease | |
| Baker et al. [37] | 2021 | In silico | Repurposing drug molecular docking | 50 compounds with activity against main protease | Main protease | Drugs including boceprevir, ciluprevir. narlaprevir, and telaprevir may be more potent against main protease than boceprevir and suitable for rapid repurposing | |
| Bharath et al. [38] | 2020 | In silico | Drug repurposing computer-aided drug design (CADD) | 4015 known and approved small molecules | Spike glycoprotein | Glycyrrhizic acid (GA) of plant origin may be repurposed for SARS-CoV-2 intervention | |
| Bhowmik et al. [39] | 2021 | In silico | Repurposing drugs, docking, and molecular dynamic simulation | Orientin (phytochemical) | Inhibitor of SARS-CoV-2 spike and host cell receptor GRP78 binding | Binding of orientin in the overlapping residues of GRP78 binding region of SARS-CoV-2 spike model | As a promising precautionary or therapeutic measure for COVID-19 |
| Bolelli et al. [40] | 2021 | In silico | Drug repurposing, virtual screening method | FDA-approved drugs | Main protease | Three compounds (dobutamine and its two derivatives) | |
| Cavasotto et al. [41] | 2021 | In silico | Drug repurposing, docking-based screening using a quantum mechanical scoring | FDA-approved drugs | Spike protein, main protease papain-like protease | Sovaprevir, elbasvir, danoprevir, samatasvir, Candesartan, saquinavir ritonavir, indinavir, lopinavir, brilacidin, flovagatran, aplidin, desmopressin, and felypressin listed as potential inhibitors of main protease | |
| Chandel et al. [42] | 2020 | In silico | Drug repurposing, molecular dynamics, and docking | FDA-approved drugs | Nsp9 replicase and spike proteins | Conivaptan exhibited the highest binding of the Nsp9 replicase. Tegobuvir exhibited maximum stability along with the highest binding energy at the active site of the spike proteins | |
| Chen et al. [43] | 2020 | In silico | Drug repurposing, molecular dynamics, and docking | FDA-approved drugs | Spike (S)-mediated cell entry | Cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol | |
| Chidambaram et al. [44] | 2020 | In silico | Molecular docking | Coumarins and their analogs | Main protease | Natural coumarin analog toddacoumaquinone displayed remarkable inhibition ability. Synthetic coumarin analog (1 m) also displayed the comparable inhibition ability main protease in intricate with α-ketoamide | |
| Choudhary et al. [45] | 2020 | In silico | Drug repurposing, molecular dynamics, and docking | FDA-approved drugs | Spike glycoprotein and cellular angiotensin-converting enzyme 2 (ACE2) receptor | GR 127935 hydrochloride hydrate, GNF-5, RS504393, TNP, and eptifibatide acetate were found binding to virus binding motifs of ACE2 receptor. KT203, BMS195614, KT185, RS504393, and GSK1838705A were identified to bind at the receptor-binding site on the viral S protein | |
| Clemente et al. [46] | 2021 | In silico | Molecular docking, molecular dynamic (MD) simulations | Ibuprofen | Main protease | Racemic mixtures of the ibuprofen enantiomers might be a potential treatment for main protease | |
| Cosic et al. [47] | 2021 | In silico | Extended resonant recognition model (RRM) | Ivermectin | Spike proteins | Ivermectin could interfere with activity of spike proteins | |
| Daoud et al. [48] | 2021 | In silico | Structure-based pharmacophore approach, molecular docking, and repurposing studies | FDA-approved drugs | Main protease | Lopinavir, remdesivir, ritonavir, saquinavir, and raltegravir were successfully docked into the binding site of main protease | |
| de Oliveira et al. [49] | 2021 | In silico | Molecular modeling and virtual screening and repurposing studies | 9091 FDA-approved drugs | Spike protein | 24 best scored ligands (14 traditional herbal isolates and 10 approved drugs) as potential candidates to inhibit the S protein | Quinupristin, nilotinib, acetyldigitoxin |
| Delijewski and Haneczok [50] | 2021 | In silico | Supervised machine learning model and repurposing studies | FDA-approved drugs | Against SARS-CoV-2 | Zafirlukast as the best repurposing candidate for COVID-19 | |
| Dey et al. [51] | 2021 | In silico | Virtual database screening, molecular docking, all-atom molecular dynamic simulation, and MM-PBSA analysis | Tretinoin, mefenamic acid, ondansetron, and artemether | Envelope (E) protein | Tretinoin as a potential SARS-CoV-2 E protein ion channel blocker and virus assembly inhibitor | |
| Durdagi [52] | 2020 | In silico | Molecular modeling approach in virtual drug screening repurposing study | FDA-approved drugs | Type 2 transmembrane serine protease (TMPRSS2) | Benzquercin as strong TMPRSS2 inhibitor | |
| Durdagi et al. [53] | 2020 | In silico | Molecular docking, MM-GBSA-based predictions, and molecular dynamic repurposing study | FDA-approved drugs | Main protease and spike receptor-binding domain bound with ACE2 COVID-19 target proteins | Pimelautide, rotigaptide, telinavir, ritonavir, pinokalant, terlakiren, cefotiam, and cefpiramide as SARS-CoV-2 main protease inhibitors. Denopamine, bometolol, naminterol, rotigaptide, and benzquercin as potential ACE2/spike protein domain inhibitors | |
| Eleftheriou et al. [54] | 2020 | In silico | Molecular docking | 34 approved and on-trial protease inhibitors | Main protease | HCV protease, DPP-4, α-thrombin, and coagulation factor Xa known inhibitors | |
| Elmezayen et al. [55] | 2021 | In silico | Molecular modeling approach in virtual drug screening repurposing study | Commercially available drugs and ZINC15 library | Main proteases | Four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone), and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889) | |
| Encinar et al. [56] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study | 9000 US Food and Drug Administration (FDA)-approved investigational and experimental drugs from the DrugBank repository | S-Adenosyl-L-methionine-binding pocket of nsp16, [2] the unique “activating surface” between nsp16 and nsp10, and [3] the RNA-binding groove of nsp16 | Tegobuvir, sonidegib, siramesine, antrafenine, bemcentinib, itacitinib, or phthalocyanine antagonism of SARS-CoV-2 RNAs lacking 20-O-methylation | |
| Farag et al. [57] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study | 2000 FDA-approved drugs | Main protease | Darunavir, nelfinavir, and saquinavir bound to the central site of main protease substrate-binding pocket rosuvastatin, montelukast, and the anti-histaminic fexofenadine bound to the terminal site of main protease substrate-binding pocket | Starting point for further in vitro and in vivo testing |
| Feng et al. [58] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study | FDA-approved drugs | Spike protein | Eltrombopag possesses a high binding affinity to S protein plus human ACE2 | |
| Ferraz et al. [59] | 2020 | In silico | Ligand and structure-based virtual screening, repurposing study | FDA-approved drugs | Main protease | Two oral (bedaquiline and glibenclamide) and one buccal drug (miconazole) | |
| Fischer et al. [60] | 2020 | In silico | Molecular docking approach in virtual drug screening and repurposing study | Over 606 million compounds | Main protease | 12 purchasable compounds, with binding affinity to the target protease the natural compounds (−)—taxifolin and rhamnetin as potential inhibitors of main protease | |
| Gimeno et al. [61] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study | FDA-approved drugs | Main protease | Perampanel, carprofen, celecoxib, alprazolam, trovafloxacin, sarafloxacin, and ethyl biscoumacetate. Carprofen and celecoxib | Initiative for in vitro testing |
| Guo et al. [62] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study single-cell RNA sequencing | US FDA-approved drugs | Against SARS-CoV-2 | 281 FDA-approved drugs that have the potential to be effective against SARS-CoV-2 infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19 | Including the HIV protease inhibitor lopinavir/ritonavir combination (phase 4), glucocorticoid receptor agonist dexamethasone (phase 3/4), DNA replication inhibitor niclosamide (phase 2/3), antineoplastic agent lenalidomide (phase 4), and calcineurin inhibitor tacrolimus (phase 3), ABT-737 (BCL inhibitor), brefeldin-A (protein synthesis inhibitor), indirubin (CDK inhibitor), TPCA-1 (IKK inhibitor), lopinavir (HIV protease inhibitor), GW-441756 (growth factor receptor inhibitor), treprostinil (prostacyclin analog), tyrphostin-AG-1478 (EGFR inhibitor) and epoxycholesterol (LXR agonist), fostamatinib (SYK inhibitor), VER-155008 (HSP inhibitor), KU-0063794 (MTOR inhibitor), PIK-90 (PI3K inhibitor), linsitinib (IGF-1 inhibitor), TAK-715 (p38 MAPK inhibitor), Y-27632 (Rho-associated kinase inhibitor), AZ-628 (RAF inhibitor), and lestaurtinib (FLT3 inhibitor) |
| Gupta et al. [63] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study | FDA-approved drugs | Main protease | Cobicistat is the most efficient inhibitor of Mpro both in silico and in vitro | |
| Huynh et al. [64] | 2021 | In silico | Docking and molecular dynamics and repurposing study | FDA-approved drugs | Papain-like protease | The chances of drug repurposing for PLpro might be low | |
| Ibrahim et al. [65] | 2020 | In silico | Molecular dynamic simulations, molecular docking, MM-GBSA analysis, and repurposing study | DrugBank database | Main protease | DB02388 and cobicistat (DB09065) | |
| Iftikhar et al. [66] | 2020 | In silico | Molecular modeling approach in virtual drug screening and repurposing study | 4574 compounds also containing FDA-approved drugs | RdRp, main protease, and helicase | Rimantadine, bagrosin, and grazoprevir showed binding to main protease. Casopitant is a neurokinin-1 receptor that showed binding to RdRp. Meclonazepam and oxiphenisatin showed specific interactions with helicase | |
| Jain and Mujwar [67] | 2020 | In silico | Computational drug repurposing docking simulations | 2880 FDA-approved drugs | Main protease | Metocurine, dihydroergotoxine, imatinib, daunorubicin, bromocriptine, irinotecan, azelastine, gestodene, adapalene, and simvastatin | Metocurine was chosen as a safe and effective drug candidate for developing therapy against the viral Mpro enzyme of SARS-CoV-2 for the treatment of COVID-19 |
| Jarvis et al. [68] | 2020 | In silico | Tier-based scoring system repurposing study | Clinically developed drugs | Potential repurposing against COVID-19 | Four drug classes (antimalarial amino-quinolones, selective estrogen receptor modulators (SERMs), low potency tricyclic antipsychotics, and tricyclic antidepressants) as potential drug candidates for COVID-19 | The tricyclic antipsychotics and tricyclic antidepressants were further excluded based on a high adverse event profile |
| Kadioglu et al. [69] | 2021 | In silico | Repositioning/virtual drug screening, molecular docking, and supervised machine learning algorithm drug repositioning | FDA-approved drug natural compound dataset ZINC database | Spike protein, nucleocapsid protein, and 2′-o-ribose methyltransferase | Conivaptan, paritaprevir, simeprevir, dihydroergotamine, ZINC000027215482, ZINC000252515584, loniflavone, procyanidin | |
| Kandeel et al. [70] | 2020 | In silico | Drug repurposing molecular dynamic (MD) simulations followed by molecular mechanics/generalized born surface area (MM/GBSA) binding energy calculations | 1697 clinical FDA-approved drugs | Papain-like protease | Phenformin, quercetin, and ritonavir | Phenformin was more stable than quercetin and ritonavir |
| Kandwal and Fayne [71] | 2020 | In silico | Repurposing drug computational design pharmacophore features | In-development/approved drugs | Viral nucleocapsid and nonstructural proteins | Isepamicin and streptomycin (nsp3); coenzyme-I, rutin, epigallocatechin gallate-(-), and procyanidin-b-2 (nsp7/nsp8/nsp12); paromomycin (nsp10/nsp16); olomoucine, sapropterin, tetrahydrofolic acid, INS316, and adenosine phosphate (nsp15); varespladib, hexanoic acid, citric acid, OSI-027, MK-5108, stepronin, calcium gluceptate, CPP, pirenoxine, midafotel, and maltobionic acid (nucleocapsid) | |
| Khan et al. [72] | 2020 | In silico | Drugs repurposing molecular dynamic simulation | 31 FDA-approved anti-HIV drugs, and traditional Chinese medicines (TCM) database | Main protease | Saquinavir and TCM5280805 | |
| Khan et al. [73] | 2020 | In silico | Drugs repurposing molecular docking | 23 prospective drug candidates | Main protease | Epirubicin, vapreotide, and saquinavir exhibited better binding affinity | Synergistic interaction |
| Kouznetsova et al. [74] | 2020 | In silico | Drugs repurposing molecular docking | FDA-approved drugs | Papain-like protease | Inhibitors of HIV, hepatitis C, and cytomegalovirus (CMV) demonstrated some activity | |
| Krishnaprasad et al. [75] | 2020 | In silico | Drugs repurposing molecular docking | FDA-approved library of drugs | RNA-dependent RNA polymerase | Pitavastatin, ridogrel, and rosoxacin displayed superior binding with the active site | |
| Kumar et al. [76] | 2020 | In silico | Drugs repurposing docking and molecular dynamic (MD) simulations combined with molecular mechanics/generalized born surface area (MM/GBSA) | 12 FDA-approved drugs (darunavir, indinavir, saquinavir, tipranavir, diosmin, hesperidin, rutin, raltegravir, velpatasvir, ledipasvir, rosuvastatin, and bortezomib) | Main protease | Saquinavir as a potent inhibitor of dimeric main protease | |
| Kumar et al. [77] | 2020 | In silico | Drugs repurposing molecular docking molecular dynamic simulations MM/GBSA | Withaferin A (Wi-A), withanone (Wi-N) (active withanolides of ashwagandha), and caffeic acid phenethyl ester (CAPE, bioactive ingredient of propolis) | Main protease | Wi-N and CAPE possess the potential to inhibit the functional activity of main protease | |
| Kumar et al. [78] | 2020 | In silico | Drugs repurposing molecular docking | FDA-approved drugs | Main protease | Lopinavir-ritonavir, tipranavir, and raltegravir show the best molecular interaction with the main protease | |
| Kumar et al. [79] | 2020 | In silico | Drugs repurposing molecular docking molecular dynamic simulations | FDA-approved library of drugs | Main protease | Hyaluronic acid and acarbose show strong interactions with catalytic site residues of main protease | |
| Li et al. [80] | 2020 | In silico | Drug repurposing free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions | Virtual screening of existing drugs | Main protease | 25 drugs were predicted, and 15 were confirmed as potent inhibitors of SARS-CoV-2 main protease. The most potent one is dipyridamole. Hydroxychloroquine (ki = 0.36 μM) and chloroquine (ki = 0.56 μM) were also found to potently inhibit main protease | |
| Liang et al. [81] | 2021 | In silico | Drug repurposing molecular docking | 2,631 FDA-approved small molecules | Multiple main proteins | 29 drugs that could actively interact with two or more target proteins, with 5 drugs (avapritinib, bictegravir, ziprasidone, capmatinib, and pexidartinib) being common candidates for all four key host proteins and 3 of them possessing the desirable molecular properties | |
| Lokhande et al. [82] | 2021 | In silico | Drugs repurposing molecular docking molecular dynamic simulations | FDA-approved drugs | Main protease | Mitoxantrone, leucovorin, birinapant, and dynasore | |
| Mahanta et al. [83] | 2020 | In silico | Drugs repurposing molecular docking molecular dynamic simulations | U.S. Food and Drug Administration-approved antimicrobial drugs | Main protease | Viomycin | |
| Mahdian et al. [84] | 2021 | In silico | Drugs repurposing molecular docking molecular dynamic simulations | FDA-approved drugs | Viral entry receptors (ACE2 and CD147) and integral enzyme of the viral polymerase (RdRp) | Ledipasvir, estradiol benzoate, and vancomycin and paritaprevir | |
| Marak et al. [85] | 2020 | In silico | Repurposing drug homology modeling molecular docking | 108 FDA-approved antiparasitic and anti-inflammatory drugs | 10 SARS-CoV-2 targets (PLpro, 3CLpro, RdRp, spike, helicase, NSP1, NSP3, NSP4, NSP9, and NSP16-NSP10) | Ivermectin, atovaquone, posaconazole, doxycycline, moxidectin, amphotericin B, chlortetracycline, spiramycin, sulfasalazine, parecoxib, and etoricoxib exhibited good binding affinities | |
| Mohapatra et al. [86] | 2020 | In silico | Repurposing drug machine learning (ML) technology | FDA-approved drugs | Against COVID-19 | 10 FDA-approved commercial drugs that can be used for repurposing amprenavir would probably be the most effective drug based on the selected criteria | |
| Molavi et al. [87] | 2021 | In silico | Repurposing drug molecular docking | 1760 FDA-approved drugs | RNA-dependent RNA polymerase (RdRp) and main protease | Nilotinib, imatinib, and dihydroergotamine for 3clpro and dexasone and raltegravir for RdRp. Raltegravir, an anti-HIV drug, was observed to be the best compound against RdRp based on docking binding energy dihydroergotamine is a suitable candidate for main protease | |
| Mulgaonkar et al. [88] | 2020 | In silico/in vitro | Repurposing drug molecular docking | FDA-approved drugs | Spike glycoprotein | BCR-ABL tyrosine kinase inhibitor, imatinib, inhibits SARS-CoV-2 | Via fusion inhibition |
| Mycroft-West et al. [89] | 2020 | In silico | Repurposing drug molecular docking molecular dynamic simulations | Heparin | Spike (S1) protein receptor-binding domain | Inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1-RBD | Repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 |
| Nayarisseri et al. [90] | 2020 | In silico | Shape-based machine learning assisted by molecular docking and molecular dynamic simulations. ADMET studies | 31 repurposed compounds | Main protease | Remdesivir, valrubicin, aprepitant, and fulvestrant | The novel compound nCorv-EMBS herein proposed stands as a promising inhibitor to be evaluated further for COVID-19 treatment |
| Odhar et al. [91] | 2020 | In silico | Molecular docking molecular dynamic simulations | 1615 FDA-approved drugs | Main protease | Conivaptan azelastine | |
| Ortega et al. [92] | 2020 | In silico | Repurposing drug molecular docking | Famotidine | Against SARS-CoV2 | Famotidine could interact within the catalytic site of the three proteases associated with SARS-CoV2 replication | Weak binding affinity could be reached only upon intravenous administration |
| Pandey et al. [93] | 2021 | In silico | Repurposing drug molecular docking | 9 flavonoids | Spike glycoprotein | Baicalin | |
| Parveen and Alnoman [94] | 2021 | In silico | Molecular docking molecular dynamic simulation density functional theory (DFT) ADME-Tox | FDA-approved anticancer drugs (capmatinib, pemigatinib, selpercatinib, and tucatinib) | Spike glycoprotein (S1) and the main protease | Potential of selected anticancer drugs for plausible drug development to fight COVID-19 | Capmatinib, pemigatinib, selpercatinib, and tucatinib |
| Peele et al. [95] | 2020 | In silico | Molecular docking molecular dynamic simulations | USFDA-approved drugs, plant-derived natural drugs | Main protease | Lopinavir, amodiaquine, theaflavin digallate | |
| Pinzi et al. [96] | 2021 | In silico | Drug repurposing molecular docking molecular mechanic Poisson–Boltzmann surface area (MM-PBSA) | DrugBank database | Main protease | 22 candidates with putative SARS-CoV-2 Mpro inhibitory activity. Enalkiren, ethylsulfonamide-D-Trp-Gln-p-aminobenzamidine, delparantag ritonavir and lopinavir, saquinavir | Beneficial polypharmacological effects |
| Pokhrel et al. [97] | 2020 | In silico | Drug repurposing molecular dynamic simulations | US Food and Drug Administration (FDA)-approved drugs | RNA-dependent RNA polymerase | Quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides | Quinupristin represents a potential anti-SARS-CoV-2 therapeutic |
| Ray et al. [98] | 2020 | In silico | Drug repurposing intramolecularly quenched fluorescence (IQF) peptide substrate | 774 FDA-approved drugs | Main protease | Ethacrynic acid, naproxen, allopurinol, butenafine hydrochloride, raloxifene hydrochloride, tranylcypromine hydrochloride, saquinavir mesylate | |
| Sachdeva et al. [99] | 2020 | In silico | Drug repurposing molecular docking | Antimalarial drugs | Spike protein and main protease | Doxycycline showed the most effective binding to the spike protein, whereas halofantrine and mefloquine bound effectively with the main protease | Doxycycline could potentially be a good candidate for repurposing for COVID-19 |
| Sang et al. [100] | 2020 | In silico | Drug repurposing molecular docking molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) | 6 approved anti-HIV drugs | Main protease | Darunavir | |
| Saxena et al. [101] | 2021 | In silico/In vitro | Drug repurposing molecular docking | FDA-approved DrugBank database | Spike protein | Ertugliflozin possesses several desired properties | Good candidate for immediate repurposing for the treatment of COVID-19 |
| Setianingsih et al. [102] | 2020 | In silico | Drug repurposing molecular docking, molecular dynamic simulations | 160 potential drugs from therapeutic target database | 13 protein targets (12 SARS-CoV-2 proteins and 1 human protein) | Suramin, the strongest binding affinity against 3 protein targets (spike protein, nucleocapsid protein, ACE2) | Suramin is the most potential to bind nucleocapsid and spike protein of SARS-CoV-2 |
| Shah et al. [103] | 2020 | In silico | Drug repurposing molecular docking | 61 molecules that are already being used in clinics or under clinical scrutiny as antiviral agents | Against the SARS-CoV-2 | 37 molecules were found to interact with >2 protein structures of COVID-19. HIV protease inhibitors and RNA-dependent RNA polymerase inhibitors showed promising features of binding to COVID-19 enzyme | Methisazone, an inhibitor of protein synthesis; CGP42112A, an angiotensin AT2 receptor agonist; and ABT450, an inhibitor of the nonstructural protein 3-4A, might become convenient treatment option as well against COVID-19 |
| Sharma and Mishra [104] | 2020 | In silico | Drug repurposing target-based virtual ligand screening | ZINC drug database and our own database of natural products | Against the SARS-CoV-2 | Antivirus drugs (ribavirin, valganciclovir, and thymidine), antibacterial drugs (cefpiramide, sulfasalazine, phenethicillin, lymecycline, demeclocycline, doxycycline, oxytetracycline, and tigecycline), anti-asthmatic drugs (montelukast, fenoterol, and reproterol), and hepatoprotective drug silybin have antiviral activity. Natural hesperidin was targeting the binding between spike RBD and human ACE2 | The natural products, such as flavonoids like neohesperidin, hesperidin, baicalin, kaempferol 3-O-rutinoside, and rutin from different sources, andrographolide, neoandrographolide, and 14-deoxy-11,12-didehydroandrographolide from A. paniculata, and a series of xanthones from the plants of Swertia genus, with antivirus, antibacteria, and anti-inflammation activity could effectively interact with these targets of SARS-CoV-2 |
| Shekhar et al. [105] | 2020 | In silico | Drug repurposing molecular docking molecular dynamic simulations | 2,625 FDA-approved small molecules | Spike (S) protein fusion peptide region | Chloramphenicol succinate, imipenem, and imidurea | |
| Singh et al. [106] | 2021 | In silico | Drug repurposing molecular docking molecular dynamic simulations | 1749 FDA-approved drugs | NSP12, a RNA polymerase | 5 compounds which include 3a (paritaprevir), 3d (glecaprevir), 3h (velpatasvir), 3j (remdesivir), and 3l (ribavirin) had the best binding affinity | |
| Sinha et al. [107] | 2021 | In silico | Drug repurposing systematic pharmacokinetics, drug-likeness, basicity predictions, virtual screening, and molecular dynamic analysis | Hydroxychloroquine (HCQ), chloroquine (CQ) | Spike protein | 1-[1-(6-Chloroquinolin-4-yl) piperidin-4-yl]piperidin-3-ol and (1r,2R)-2-N-(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine interact with the active site of the spike protein similar to HCQ and CQ, respectively, with augmented safety profile | |
| Soni et al. [108] | 2020 | In silico | Molecular docking molecular dynamic simulation ADME properties | Rifampicin | Main protease | Rifampicin docking score was −7.24 kcal·mol–1, and it can predict as a very good inhibitor of main protease | |
| Tariq et al. [109] | 2020 | In silico | Drug repurposing molecular docking molecular dynamic simulations | 15 antimalarial drugs (including chloroquine) and 2413 US Food and Drug Administration-approved drugs | Main protease spike (S) protein | Paromomycin with activity against two targets spike protein and protease domain | |
| Tatar et al. [110] | 2021 | In silico | Drug repurposing molecular docking molecular dynamic simulations | 34 antiviral compounds | RNA-binding domain | Rapamycin, saracatinib, camostat, trametinib, and nafamostat were the top hit compounds | |
| Tejera et al. [111] | 2020 | In silico | Drug repurposing quantitative structure-activity relationship (QSAR) mode molecular docking molecular dynamic simulation MM-PBSA method | DrugBank database | Main protease | Levothyroxine, amobarbital, and ABP-700 | |
| Teralı et al. [112] | 2020 | In silico | Drug repurposing molecular docking | 7,173 clinically approved drug | Angiotensin-converting enzyme 2 (ACE2) | Lividomycin, burixafor, quisinostat, fluprofylline, pemetrexed, spirofylline, edotecarin, diniprofylline | |
| Trezza et al. [113] | 2020 | In silico | Drug repurposing docking simulations, with molecular dynamics (MD), supervised MD (SuMD), and steered MD (SMD) simulations | FDA-approved drugs | Spike glycoprotein | Simeprevir, lumacaftor | |
| Ugurel et al. [114] | 2020 | In silico | Drug repurposing structure-based drug design genome sequences were analyzed | FDA-approved drugs | Helicase (Nsp13) | Cangrelor, fludarabine, folic acid, and polydatin inhibit both the wild-type and mutant SARS-CoV-2 helicase | |
| Unni et al. [115] | 2020 | In silico | Drug repurposing molecular docking molecular dynamic simulations | DrugBank and PubChem library | Spike protein (S protein) | Bisoxatin (DB09219) | A laxative drug |
| Vaishali et al. [116] | 2020 | In silico | Drug repurposing molecular docking molecular dynamic simulation ADME properties | FDA-approved compounds | Nonstructural protein 9 (Nsp9) replicase and spike proteins | Conivaptan exhibited the highest binding energy and maximum stability of the Nsp9 replicase. Tegobuvir exhibited maximum stability along with the highest binding energy at the active site of the spike proteins | |
| Verma et al. [117] | 2020 | In silico | Drug repurposing molecular docking molecular dynamic simulation MM-GBSA-based energy | FDA-approved drugs | Main protease | Top-ranked drugs including adefovir, lumefantrine, dipyridamole, dihydroergotamine, hexoprenaline, riboflavin (vitamin B2), and pantethine (vitamin B5) | |
| Wei et al. [118] | 2020 | In silico | Drug repurposing molecular docking molecular dynamic simulations | US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from traditional Chinese medicine systems pharmacology (TCMSP) | Spike protein (S protein) | Digitoxin and bisindigotin in TCMSP had the highest docking scores Forsythiae fructus and Isatidis radix are components of Lianhua Qingwen, and raltegravir had relatively high binding scores | |
| Xu et al. [119] | 2021 | In silico | Drug repurposing molecular docking molecular dynamic simulations | FDA-approved drugs | Spike protein | Thymoquinone, a phytochemical compound obtained from the plant Nigella sativa, is a potential drug candidate | |
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