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1.
Molecules ; 26(4)2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1110462

ABSTRACT

Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that has been shown to reduce virus replication, and its high-resolution 3D structures in complex with inhibitors have been solved. Previously, we had demonstrated the potential of natural compounds such as serine protease inhibitors eventually leading us to hypothesize that FDA-approved marine drugs have the potential to inhibit the biological activity of SARS-CoV-2 main protease. Initially, field-template and structure-activity atlas models were constructed to understand and explain the molecular features responsible for SARS-CoVID-2 main protease inhibitors, which revealed that Eribulin Mesylate, Plitidepsin, and Trabectedin possess similar characteristics related to SARS-CoVID-2 main protease inhibitors. Later, protein-ligand interactions are studied using ensemble molecular-docking simulations that revealed that marine drugs bind at the active site of the main protease. The three-dimensional reference interaction site model (3D-RISM) studies show that marine drugs displace water molecules at the active site, and interactions observed are favorable. These computational studies eventually paved an interest in further in vitro studies. Finally, these findings are new and indeed provide insights into the role of FDA-approved marine drugs, which are already in clinical use for cancer treatment as a potential alternative to prevent and treat infected people with SARS-CoV-2.


Subject(s)
Peptide Hydrolases/chemistry , Peptide Hydrolases/metabolism , SARS-CoV-2/physiology , Serine Proteinase Inhibitors/pharmacology , Catalytic Domain , Depsipeptides/chemistry , Depsipeptides/pharmacology , Drug Repositioning , Furans/chemistry , Furans/pharmacology , Humans , Ketones/chemistry , Ketones/pharmacology , Models, Molecular , Molecular Docking Simulation , Peptides, Cyclic , Quantitative Structure-Activity Relationship , SARS-CoV-2/drug effects , Serine Proteinase Inhibitors/chemistry , Trabectedin/chemistry , Trabectedin/pharmacology , Viral Proteins/antagonists & inhibitors , Virus Replication/drug effects
2.
Comput Biol Med ; 131: 104295, 2021 04.
Article in English | MEDLINE | ID: covidwho-1095921

ABSTRACT

Papain-Like Protease (PLpro) is a key protein for SARS-CoV-2 viral replication which is the cause of the emerging COVID-19 pandemic. Targeting PLpro can suppress viral replication and provide treatment options for COVID-19. Due to the dynamic nature of its binding site loop, PLpro multiple conformations were generated through a long-range 1 micro-second molecular dynamics (MD) simulation. Clustering the MD trajectory enabled us to extract representative structures for the conformational space generated. Adding to the MD representative structures, X-ray structures were involved in an ensemble docking approach to screen the FDA approved drugs for a drug repositioning endeavor. Guided by our recent benchmarking study of SARS-CoV-2 PLpro, FRED docking software was selected for such a virtual screening task. The results highlighted potential consensus binders to many of the MD clusters as well as the newly introduced X-ray structure of PLpro complexed with a small molecule. For instance, three drugs Benserazide, Dobutamine and Masoprocol showed a superior consensus enrichment against the PLpro conformations. Further MD simulations for these drugs complexed with PLpro suggested the superior stability and binding of dobutamine and masoprocol inside the binding site compared to Benserazide. Generally, this approach can facilitate identifying drugs for repositioning via targeting multiple conformations of a crucial target for the rapidly emerging COVID-19 pandemic.


Subject(s)
Coronavirus 3C Proteases , Cysteine Proteinase Inhibitors/chemistry , Drug Repositioning , Molecular Dynamics Simulation , SARS-CoV-2/enzymology , Binding Sites , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Enzyme Stability , Humans
3.
Front Chem ; 8: 595273, 2020.
Article in English | MEDLINE | ID: covidwho-1069717

ABSTRACT

The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, and both encode the enzyme main protease (Mpro/3CLpro), which can be a potential target inhibiting viral replication. Through this work, we have compiled the structural aspects of Mpro conformational changes, with molecular modeling and 1-µs MD simulations. Long-scale MD simulation resolves the mechanism role of crucial amino acids involved in protein stability, followed by ensemble docking which provides potential compounds from the Traditional Chinese Medicine (TCM) database. These lead compounds directly interact with active site residues (His41, Gly143, and Cys145) of Mpro, which plays a crucial role in the enzymatic activity. Through the binding mode analysis in the S1, S1', S2, and S4 binding subsites, screened compounds may be functional for the distortion of the oxyanion hole in the reaction mechanism, and it may lead to the inhibition of Mpro in SARS-CoV-2. The hit compounds are naturally occurring compounds; they provide a sustainable and readily available option for medical treatment in humans infected by SARS-CoV-2. Henceforth, extensive analysis through molecular modeling approaches explained that the proposed molecules might be promising SARS-CoV-2 inhibitors for the inhibition of COVID-19, subjected to experimental validation.

4.
Drug Dev Res ; 82(4): 469-473, 2021 06.
Article in English | MEDLINE | ID: covidwho-1047152

ABSTRACT

Despite vigorous efforts, the COVID-19 pandemic continues to take a toll on the global health. The contemporary therapeutic regime focused on the viral spike proteins, viral 3CL protease enzyme, immunomodulation, inhibition of viral replication, and providing a symptomatic relief encouraged the repurposing of drugs to meet the urgency of treatment. Similarly, the representative drugs that proved beneficial to alleviate SARS-CoV-1, MERS-CoV, HIV, ZIKV, H1N1, and malarial infection in the past presented a sturdy candidature for ameliorating the COVID-19 therapeutic doctrine. However, most of the deliberations for developing effective pharmaceuticals proved inconsequential, thereby encouraging the identification of new pathways, and novel pharmaceuticals for capping the COVID-19 infection. The COVID-19 contagion encompasses a burst release of the cytokines that increase the severity of the infection mainly due to heightened immunopathogenicity. The pro-inflammatory metabolites, COX-2, cPLA2, and 5-LOX enzymes involved in their generation, and the substrates that instigate the origination of the innate inflammatory response therefore play an important role in intensifying and worsening of the tissue morbidity related to the coronavirus infection. The deployment of representative drugs for inhibiting these overexpressed immunogenic pathways in the tissues invaded by coronaviruses has been a matter of debate since the inception of the pandemic. The effectiveness of NSAIDs such as Aspirin, Indomethacin, Diclofenac, and Celecoxib in COVID-19 coagulopathy, discouraging the SARS viral replication, the inflammasome deactivation, and synergistic inhibition of H5N1 viral infection with representative antiviral drugs respectively, have provided a silver lining in adjuvant COVID-19 therapy. Since the anti-inflammatory NSAIDs and COXIBs mainly function by reversing the COX-2 overexpression to modulate the overproduction of pro-inflammatory cytokines and chemokines, these drugs present a robust treatment option for COVID-19 infection. This commentary succinctly highlights the various claims that support the status of immunomodulatory NSAIDs, and COXIBs in the adjuvant COVID-19 therapy.


Subject(s)
COVID-19/enzymology , Immunologic Factors/therapeutic use , Prostaglandin-Endoperoxide Synthases/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/drug therapy , Chemotherapy, Adjuvant/methods , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Humans , Immunologic Factors/pharmacology , Prostaglandin-Endoperoxide Synthases/drug effects , Prostaglandin-Endoperoxide Synthases/physiology
5.
Structure ; 28(12): 1313-1320.e3, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-997553

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 requires rapid development of specific therapeutics and vaccines. The main protease of SARS-CoV-2, 3CL Mpro, is an established drug target for the design of inhibitors to stop the virus replication. Repurposing existing clinical drugs can offer a faster route to treatments. Here, we report on the binding mode and inhibition properties of several inhibitors using room temperature X-ray crystallography and in vitro enzyme kinetics. The enzyme active-site cavity reveals a high degree of malleability, allowing aldehyde leupeptin and hepatitis C clinical protease inhibitors (telaprevir, narlaprevir, and boceprevir) to bind and inhibit SARS-CoV-2 3CL Mpro. Narlaprevir, boceprevir, and telaprevir are low-micromolar inhibitors, whereas the binding affinity of leupeptin is substantially weaker. Repurposing hepatitis C clinical drugs as COVID-19 treatments may be a useful option to pursue. The observed malleability of the enzyme active-site cavity should be considered for the successful design of specific protease inhibitors.


Subject(s)
Antiviral Agents , Betacoronavirus , COVID-19 , Coronavirus Infections , Antiviral Agents/pharmacology , Betacoronavirus/metabolism , Catalytic Domain , Coronavirus Infections/drug therapy , Crystallography, X-Ray , Cysteine Endopeptidases/metabolism , Humans , Pandemics , Protease Inhibitors/pharmacology , SARS-CoV-2 , Temperature , Viral Nonstructural Proteins
6.
Biochem Biophys Res Commun ; 537: 71-77, 2021 01 22.
Article in English | MEDLINE | ID: covidwho-987123

ABSTRACT

The sanitary emergency generated by the pandemic COVID-19, instigates the search for scientific strategies to mitigate the damage caused by the disease to different sectors of society. The disease caused by the coronavirus, SARS-CoV-2, reached 216 countries/territories, where about 20 million people were reported with the infection. Of these, more than 740,000 died. In view of the situation, strategies involving the development of new antiviral molecules are extremely important. The present work evaluated, through molecular docking assays, the interactions of 4'-acetamidechalcones with enzymatic and structural targets of SARS-CoV-2 and with the host's ACE2, which is recognized by the virus, facilitating its entry into cells. Therefore, it was observed that, regarding the interactions of chalcones with Main protease (Mpro), the chalcone N-(4'[(2E)-3-(4-flurophenyl)-1-(phenyl)prop-2-en-1-one]) acetamide (PAAPF) has the potential for coupling in the same region as the natural inhibitor FJC through strong hydrogen bonding. The formation of two strong hydrogen bonds between N-(4[(2E)-3-(phenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAB) and the NSP16-NSP10 heterodimer methyltransferase was also noted. N-(4[(2E)-3-(4-methoxyphenyl)-1-(phenyl)prop-2-en-1-one]) acetamide (PAAPM) and N-(4-[(2E)-3-(4-ethoxyphenyl)-1-(phenyl)prop-2-en-1-one]) acetamide (PAAPE) chalcones showed at least one strong intensity interaction of the SPIKE protein. N-(4[(2E)-3-(4-dimetilaminophenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAPA) chalcone had a better affinity with ACE2, with strong hydrogen interactions. Together, our results suggest that 4'-acetamidechalcones inhibit the interaction of the virus with host cells through binding to ACE2 or SPIKE protein, probably generating a steric impediment. In addition, chalcones have an affinity for important enzymes in post-translational processes, interfering with viral replication.


Subject(s)
Acetamides/chemistry , Acetamides/pharmacology , Angiotensin-Converting Enzyme 2/chemistry , Antiviral Agents/pharmacology , Chalcone/analogs & derivatives , Coronavirus 3C Proteases/chemistry , Molecular Docking Simulation , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Chalcone/chemistry , Chalcone/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Humans , Microbial Sensitivity Tests , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Virus Replication/drug effects
7.
J Proteome Res ; 20(1): 1015-1026, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-989661

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a multifunctional papain-like proteinase (PLpro), which mediates the processing of the viral replicase polyprotein. Inhibition of PLpro has been shown to suppress the viral replication. This study aimed to explore new anti-PLpro candidates by applying virtual screening based on GRL0617, a known PLpro inhibitor of SARS coronavirus (SARS-CoV). The three-dimensional (3D) structure of SARS-CoV-2 PLpro was built by homology modeling, using SARS-CoV PLpro as the template. The model was refined and studied through molecular dynamic simulation. AutoDock Vina was then used to perform virtual screening where 50 chemicals with at least 65% similarity to GRL0617 were docked with the optimized SARS-CoV-2 PLpro. In this screening, 5-(aminomethyl)-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide outperformed GRL0617 in terms of binding affinity (-9.7 kcal/mol). Furthermore, 2-(4-fluorobenzyl)-5-nitro-1H-isoindole-1,3(2H)-dione (previously introduced as an inhibitor of cyclooxygenase-2), 3-nitro-N-[(1r)-1-phenylethyl]-5-(trifluoromethyl)benzamide (inhibitor against Mycobacterium tuberculosis), as well as the recently introduced SARS-CoV-2 PLpro inhibitor 5-acetamido-2-methyl-N-[(1S)-1-naphthalen-1-ylethyl]benzamide showed promising affinity for the viral proteinase. All of the identified compounds demonstrated an acceptable pharmacokinetic profile. In conclusion, our findings represent rediscovery of analgesic, anti-inflammatory, antibacterial, or antiviral drugs as promising pharmaceutical candidates against the ongoing coronavirus.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Protease Inhibitors/pharmacology , Antiviral Agents/adverse effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Binding Sites , Chemical and Drug Induced Liver Injury/etiology , Computer Simulation , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Evaluation, Preclinical/methods , Humans , Microsomes, Liver/drug effects , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/adverse effects , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacokinetics , Protein Conformation , Structure-Activity Relationship
8.
J Biomol Struct Dyn ; 40(9): 4110-4121, 2022 06.
Article in English | MEDLINE | ID: covidwho-966751

ABSTRACT

The pandemic disease COVID-19, caused by SARS CoV-2, has created a global crisis. Presently, researchers across the globe are in a quest to identify/develop drugs or vaccines by targeting different non-structural proteins (Nsps) of SARS CoV-2. One such important drug target is Nsp5/main protease (Mpro) which plays a critical role in the viral replication. This cysteine protease/Mpro of SARS CoV-2 has high sequence similarity with the same protease from SARS CoV-1. Previously, it has been shown experimentally that eight polyphenols derived from the root of Isatis indigotica show inhibitory effect on the cleavage/catalytic activity of the SARS CoV-1 Mpro. But whether these polyphenols exhibit any inhibitory effect on SARS CoV-2 Mpro is unclear. To explore this possibility, here, we have adopted various computational approaches. Polyphenols that qualified the pharmacological parameters (indigo, sinigrin, hesperetin and daidzein) and two well-known Mpro inhibitors (N3 and lopinavir) were subjected to molecular docking studies. Two of them (sinigrin and hesperetin) were selected by comparing their binding affinities with N3 and lopinavir. Sinigrin and hesperetin interacted with the two most important catalytic residues of Mpro (His41 and Cys145). Molecular dynamics studies further revealed that these two Mpro-polyphenol complexes are more stable and experience less conformational fluctuations than Mpro-N3/lopinavir complex. The Mpro-hesperetin complex was more compact and less expanded than Mpro-sinigrin complex. These findings were additionally validated by MM-GBSA analysis. As a whole, our study revealed that these two polyphenols may be potent SARS CoV-2 Mpro inhibitors and may possibly be considered for COVID-19 treatment.


Subject(s)
Antiviral Agents , Coronavirus 3C Proteases , Isatis , Protease Inhibitors , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Humans , Isatis/chemistry , Lopinavir , Molecular Docking Simulation , Molecular Dynamics Simulation , Polyphenols/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects
9.
J Biomol Struct Dyn ; 40(8): 3745-3752, 2022 05.
Article in English | MEDLINE | ID: covidwho-939481

ABSTRACT

Spike protein and main proteases of SARS-CoV-2 have been identified as potential therapeutic targets and their inhibition may lead to the reticence of viral entry and replication in the host body. Despite several efforts; till now no specific drugs are available to treat SARS-CoV-2. Considering all these challenges, the main objective of the present study was to establish therapeutic potential of cordycepin against COVID-19 as a conventional therapeutic strategy. In the present study; molecular interaction study was performed to assess potential binding affinity of cordycepin with SARS-CoV-2 target proteins using computational approach. Additionally, network pharmacology was used to understand cordycepin-protein interactions and their associated pathways in human body. Cordycepin is under clinical trial (NCT00709215) and possesses structural similarity with adenosine except that, it lacks a 3' hydroxyl group in its ribose moiety and hence it served as a poly(A) polymerase inhibitor and terminate premature protein synthesis. Additionally, it is known that functional RNAs of SARS-CoV-2 genome are highly 3'-plyadenylated and leading to synthesis of all viral proteins and if cordycepin can destabilize SARS-CoV-2 RNAs by inhibiting polyadenylation process then it may step forward in terms of inhibition of viral replication and multiplication in the host. Moreover, cordycepin showed strong binding affinity with SARS-CoV-2 spike protein (-145.3) and main proteases (-180.5) that further corroborate therapeutic potential against COVID-19. Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of COVID-19.


Subject(s)
COVID-19 , Cordyceps , Antiviral Agents/chemistry , COVID-19/drug therapy , Clinical Trials as Topic , Cordyceps/metabolism , Deoxyadenosines , Humans , Peptide Hydrolases/metabolism , Polyadenylation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
10.
J Biomol Struct Dyn ; 40(8): 3609-3625, 2022 05.
Article in English | MEDLINE | ID: covidwho-939480

ABSTRACT

COVID-19 pandemic has created a healthcare crisis across the world and has put human life under life-threatening circumstances. The recent discovery of the crystallized structure of the main protease (Mpro) from SARS-CoV-2 has provided an opportunity for utilizing computational tools as an effective method for drug discovery. Targeting viral replication has remained an effective strategy for drug development. Mpro of SARS-COV-2 is the key protein in viral replication as it is involved in the processing of polyproteins to various structural and nonstructural proteins. Thus, Mpro represents a key target for the inhibition of viral replication specifically for SARS-CoV-2. We have used a virtual screening strategy by targeting Mpro against a library of commercially available compounds to identify potential inhibitors. After initial identification of hits by molecular docking-based virtual screening further MM/GBSA, predictive ADME analysis, and molecular dynamics simulation were performed. The virtual screening resulted in the identification of twenty-five top scoring structurally diverse hits that have free energy of binding (ΔG) values in the range of -26-06 (for compound AO-854/10413043) to -59.81 Kcal/mol (for compound 329/06315047). Moreover, the top-scoring hits have favorable AMDE properties as calculated using in silico algorithms. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential SARS-CoV-2 Mpro hit compounds with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop novel Mpro inhibitors to tackle this pandemic.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Molecular Dynamics Simulation , COVID-19/drug therapy , Coronavirus 3C Proteases , Humans , Molecular Docking Simulation , Pandemics , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , SARS-CoV-2
11.
J Biomol Struct Dyn ; 39(17): 6747-6760, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-695712

ABSTRACT

The current COVID-19 pandemic is caused by SARS CoV-2. To date, ∼463,000 people died worldwide due to this disease. Several attempts have been taken in search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro) from SARS CoV-2 plays a vital role in viral replication and thus serves as an important drug target. This Mpro shares a high degree of sequence similarity (>96%) with the same protease from SARS CoV-1 and MERS. It was already reported that Broussonetia papyrifera polyphenols efficiently inhibit the catalytic activity of SARS CoV-1 and MERS Mpro. But whether these polyphenols exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To understand this fact, here we have adopted computational approaches. Polyphenols having proper drug-likeness properties and two repurposed drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only six polyphenols (broussochalcone A, papyriflavonol A, 3'-(3-methylbut-2-enyl)-3',4',7-trihydroxyflavane, broussoflavan A, kazinol F and kazinol J) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.6 to -8.2 kcal/mol). Molecular dynamic simulations (100 ns) revealed that all Mpro-polyphenol complexes are more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bond and MM-GBSA analysis suggested that these six polyphenols are more potent Mpro inhibitors than the two repurposed drugs (lopinavir and darunavir) and may serve as promising anti-COVID-19 drugs.


Subject(s)
Broussonetia , COVID-19 , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Polyphenols , Protease Inhibitors/pharmacology , SARS-CoV-2
12.
J Biomol Struct Dyn ; 39(10): 3733-3746, 2021 07.
Article in English | MEDLINE | ID: covidwho-378264

ABSTRACT

The recent pandemic of severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection (COVID-19) has put the world on serious alert. The main protease of SARS-CoV-2 (SARS-CoV-2-MPro) cleaves the long polyprotein chains to release functional proteins required for replication of the virus and thus is a potential drug target to design new chemical entities in order to inhibit the viral replication in human cells. The current study employs state of art computational methods to design novel molecules by linking molecular fragments which specifically bind to different constituent sub-pockets of the SARS-CoV-2-MPro binding site. A huge library of 191678 fragments was screened against the binding cavity of SARS-CoV-2-MPro and high affinity fragments binding to adjacent sub-pockets were tailored to generate new molecules. These newly formed molecules were further subjected to molecular docking, ADMET filters and MM-GBSA binding energy calculations to select 17 best molecules (named as MP-In1 to MP-In17), which showed comparable binding affinities and interactions with the key binding site residues as the reference ligand. The complexes of these 17 molecules and the reference molecule with SARS-CoV-2-MPro, were subjected to molecular dynamics simulations, which assessed the stabilities of their binding with SARS-CoV-2-MPro. Fifteen molecules were found to form stable complexes with SARS-CoV-2-MPro. These novel chemical entities designed specifically according to the pharmacophoric requirements of SARS-CoV-2-MPro binding pockets showed good synthetic feasibility and returned no exact match when searched against chemical databases. Considering their interactions, binding efficiencies and novel chemotypes, they can be further evaluated as potential starting points for SARS-CoV-2 drug discovery.


Subject(s)
Antiviral Agents , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Drug Design , Molecular Docking Simulation , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects
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