Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19

Faheem, Faheem; Kumar, Banoth Karan; Sekhar, Kondapalli Venkata Gowri Chandra; Kunjiappan, Selvaraj; Jamalis, Joazaizulfazli; Balaña‐Fouce, Rafael; Tekwani, Babu L.; Murugesan, Sankaranarayanan

doi:10.1016/j.bioorg.2020.104269

Cited by 86 publications

(77 citation statements)

References 153 publications

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“…Altogether, these features make our server of interest even for advanced users, adding robustness to docking analysis. Currently, DINC-COVID offers ensemble docking for the catalytic binding site of SARS-CoV-2 Main protease (Mpro), Papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) (Zhu et al, 2020;Aftab et al, 2020;Faheem et al, 2020), as well as the allosteric binding site of Mpro (Menéndez et al, 2020). Ensembles of other SARS-CoV-2 proteins are under process (e.g., spike protein) and will be added to the webserver, which also enables users to make requests.…”

Section: Discussionmentioning

confidence: 99%

DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins

Hall-Swan

Antunes

Devaurs

et al. 2021

Preprint

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MotivationRecent efforts to computationally identify inhibitors for SARS-CoV-2 proteins have largely ignored the issue of receptor flexibility. We have implemented a computational tool for ensemble docking with the SARS-CoV-2 proteins, including the main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp).ResultsEnsembles of other SARS-CoV-2 proteins are being prepared and made available through a user-friendly docking interface. Plausible binding modes between conformations of a selected ensemble and an uploaded ligand are generated by DINC, our parallelized meta-docking tool. Binding modes are scored with three scoring functions, and account for the flexibility of both the ligand and receptor. Additional details on our methods are provided in the supplementary material.Availabilitydinc-covid.kavrakilab.orgSupplementary informationDetails on methods for ensemble generation and docking are provided as supplementary data online.Contactgeancarlo.zanatta@ufc.br, kavraki@rice.edu

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Section: Discussionmentioning

confidence: 99%

DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins

Hall-Swan

Antunes

Devaurs

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…This enzyme also recognizes the consensus cleavage sequence identified by cellular deubiquitinating enzymes [ 87 ]. Therefore, substrate-derived inhibitors of PL pro would be expected to inhibit host cell deubiquitinases [ 41 , 76 , 87 ].…”

Section: The Importance Of Multitargets To Cadd Approaches: Pl mentioning

confidence: 99%

“…The RdRp (nsp12) has also been described as an important coronavirus target for drug design [ 41 , 44 , 45 ]. It has an essential role in the viral cycle of coronaviruses, since it is responsible for the replication of the viral genome, with the assistance of nsp7 and nsp8 viral proteins in a polymerase complex [ 39 , 94 , 95 ].…”

Section: The Importance Of Multitargets To Cadd Approaches: Pl mentioning

confidence: 99%

“…Among the molecular targets of SARS-CoV-2, main protease or 3-chymotrypsin-like protease (M pro /3CL pro /nsp5) [ 37 ], papain-like protease (PL pro /nsp3) [ 38 ], RNA-dependent RNA polymerase (RdRp/nsp12) [ 39 ], and helicase/NTPase (nsp13) [ 40 ] could be cited, which are highly conserved and essential to the viral cycle [ 36 , 41–45 ], as illustrated in Figure 2 . Since the main viral protease is extensively studied for the design of new drug candidates to treat coronaviruses diseases, and most of the studies identified this enzyme as a valid target for broad spectrum inhibitors, we will next focus on the discussion of this macromolecule in more details [ 33 , 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

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Knowing and combating the enemy: a brief review on SARS-CoV-2 and computational approaches applied to the discovery of drug candidates

et al. 2021

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Since the emergence of the new severe acute respiratory syndrome-related coronaviruses 2 (SARS-CoV-2) at the end of December 2019 in China, and with the urge of the coronavirus disease 2019 (COVID-19) pandemic, there have been a huge effort of many research teams and governmental institutions worldwide to mitigate the current scenario. Reaching more than 1,377,000 deaths in the world and still with a growing number of infections, SARS-CoV-2 remains a critical issue for global health and economic systems, with an urgency for available therapeutic options. In this scenario, as drug repurposing and discovery remains a challenge, computer-aided drug design (CADD) approaches, including machine learning (ML) techniques, can be useful tools to the design and discovery of novel potential antiviral inhibitors against SARS-CoV-2. In this work, we describe and review the current knowledge on this virus and the pandemic, the latest strategies and computational approaches applied to search for treatment options, as well as the challenges to overcome COVID-19.

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“…Notably, the components of some plants may differ based on the plant part used ( Kumar et al, 2020a ). For instance, the Citrus spp.…”

Section: Introductionmentioning

confidence: 99%

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

et al. 2021

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The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.

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Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19

Abstract: Graphical abstract

Cited by 86 publications

References 153 publications

DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins

DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins

Knowing and combating the enemy: a brief review on SARS-CoV-2 and computational approaches applied to the discovery of drug candidates

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

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