The Mpro structure-based modifications of ebselen derivatives for improved antiviral activity against SARS-CoV-2 virus

Qiao, Zhen; Wang, Ningning; Jin, Lin; Zhang, Hongyi; Luo, Jiajie; Zhang, Yanru; Wang, Kewei

doi:10.1016/j.bioorg.2021.105455

Cited by 29 publications

(28 citation statements)

References 38 publications

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“…As discussed above, ebselen analogs have also been extensively exploited as M pro and PL pro inhibitors by targeting the active-site cysteine. 102,103 Combined with the zinc-ejecting property, the antiviral activity of ebselen (55) and its derivatives might be due to its polypharmacology in targeting the ZBD, PL pro , M pro , and others.…”

Section: Sars-cov-2 Pl Pro Inhibitorsmentioning

confidence: 99%

Progress and Challenges in Targeting the SARS-CoV-2 Papain-like Protease

et al. 2022

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SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The approval of vaccines and small-molecule antivirals is vital in combating the pandemic. The viral polymerase inhibitors remdesivir and molnupiravir and the viral main protease inhibitor nirmatrelvir/ritonavir have been approved by the U.S. FDA. However, the emergence of variants of concern/interest calls for additional antivirals with novel mechanisms of action. The SARS-CoV-2 papain-like protease (PL pro ) mediates the cleavage of viral polyprotein and modulates the host’s innate immune response upon viral infection, rendering it a promising antiviral drug target. This Perspective highlights major achievements in structure-based design and high-throughput screening of SARS-CoV-2 PL pro inhibitors since the beginning of the pandemic. Encouraging progress includes the design of non-covalent PL pro inhibitors with favorable pharmacokinetic properties and the first-in-class covalent PL pro inhibitors. In addition, we offer our opinion on the knowledge gaps that need to be filled to advance PL pro inhibitors to the clinic.

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Section: Sars-cov-2 Pl Pro Inhibitorsmentioning

confidence: 99%

Progress and Challenges in Targeting the SARS-CoV-2 Papain-like Protease

et al. 2022

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“…Recently, derivatives from Ebselen as a scaffold have been developed based on the SARS-CoV-2 3CLpro structure. 70 …”

Section: Anti-inflammatory Small-molecule Drugs Targeting 3clpromentioning

confidence: 99%

Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds

Zhu¹,

Zhang²,

Lin³

et al. 2022

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently poses a threat to human health. 3C-like proteinase (3CLpro) plays an important role in the viral life cycle. Hence, it is considered an attractive antiviral target protein. Whole-genome sequencing showed that the sequence homology between SARS-CoV-2 3CLpro and SARS-CoV 3CLpro is 96.08%, with high similarity in the substrate-binding region. Thus, assessing peptidomimetic inhibitors of SARS-CoV 3CLpro could accelerate the development of peptidomimetic inhibitors for SARS-CoV-2 3CLpro. Accordingly, we herein discuss progress on SARS-CoV-2 3CLpro peptidomimetic inhibitors. Inflammation plays a major role in the pathophysiological process of COVID-19. Small-molecule compounds targeting 3CLpro with both antiviral and anti-inflammatory effects are also briefly discussed in this paper.

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“…The molecular docking was employed to study the interactions between these complexes and the main proteases (MPros) of the SARS-CoV-2 virus (PDB IDs: 6LU7, 6WQF, and 6W9C) [ [12] , [13] ]. The studied MPros are shown to be the key for SARS-CoV-2 virus replication which makes it the potent target for inhibitor drugs [ [14] , [15] , [16] ]. Our results show that the synthesized complexes showed great interaction with the studied three main proteases of COVID-19.…”

Section: Introductionmentioning

confidence: 99%