SARS-CoV-2: Potential Drug Targets and Its Virtual Screening

Dubey, Raghvendra; Dubey, Kushagra

doi:10.1007/978-3-030-72834-2_8

Cited by 4 publications

(2 citation statements)

References 186 publications

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“…Three domains have been identified in the crystal structure of SAR-CoV-2 PLpro, which highlights the catalytic cysteine cleavage domain, a potential labile Zn-binding domain, and a ubiquitin domain [63]. The labile ZnII ion is essential for preserving the structural integrity of SAR CoV-2 PLpro, while the catalytic site, is defined by the amino acid triad Cys111-His272-Asp286 [64]. All of these domains are viable targets for therapy because the ubiquitin domain is connected to the hostʹs innate immune responses [65].…”

Section: Structure and Function Of Sars-cov-2 Plpromentioning

confidence: 99%

“…Despite having less research done on it than Mpro, PLpro is a multifunctional protein that functions as a deubiquitinase and a cysteine protease, which opens the door for the development of powerful PLpro inhibitors [64]. This special combination of roles affects host immune responses in addition to viral protein processing [64]. Thus, PLpro is an appealing target for antivirals since blocking its functions may prevent viral replication and interfere with host immune systems [76].…”

Section: Structure and Function Of Sars-cov-2 Plpromentioning

confidence: 99%

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Mechanistic Insights into Targeting SARS-CoV-2 Papain-Like Protease in the Evolution and Management of COVID-19: A Comprehensive Review

MAGWAZA,

MUSHEBENGE,

UGBAJA

et al. 2023

Preprint

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The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

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Section: Structure and Function Of Sars-cov-2 Plpromentioning

confidence: 99%

Section: Structure and Function Of Sars-cov-2 Plpromentioning

confidence: 99%

Mechanistic Insights into Targeting SARS-CoV-2 Papain-Like Protease in the Evolution and Management of COVID-19: A Comprehensive Review

MAGWAZA,

MUSHEBENGE,

UGBAJA

et al. 2023

Preprint

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Integration of LC/MS, NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti‐SARS‐CoV‐2 Activity

Essa¹,

El‐Hawary

Kubacy³

et al. 2023

Chemistry & Biodiversity

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In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC 50 8.231 � 0.04 μg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.

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Proposing lead compounds for the development of SARS-CoV-2 receptor-binding inhibitors

Awuni

Musah

2023

Journal of Biomolecular Structure and Dynamics

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SARS-CoV-2: Potential Drug Targets and Its Virtual Screening

Cited by 4 publications

References 186 publications

Mechanistic Insights into Targeting SARS-CoV-2 Papain-Like Protease in the Evolution and Management of COVID-19: A Comprehensive Review

Mechanistic Insights into Targeting SARS-CoV-2 Papain-Like Protease in the Evolution and Management of COVID-19: A Comprehensive Review

Integration of LC/MS, NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti‐SARS‐CoV‐2 Activity

Proposing lead compounds for the development of SARS-CoV-2 receptor-binding inhibitors

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