Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay

Narayanan, A.; Narwal, M.; Majowicz, Sydney A.; Varricchio, Carmine; Toner, Shay A; Ballatore, Carlo; Brancale, Andrea; Murakami, Katsuhiko; Jose, Joyce

doi:10.1038/s42003-022-03090-9

Cited by 165 publications

(124 citation statements)

References 77 publications

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“…300 – 302 Studies also pointed out that combinatorial use of 3CLpro and Mpro inhibitors could significantly inhibit SARS-CoV-2 variants, broadening the use of drugs targeting these two proteins. 303 , 304 …”

Section: Molecular Characteristics Of Sequence and The Encoded Protei...mentioning

confidence: 99%

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Sun

Xie

et al. 2022

Sig Transduct Target Ther

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The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.

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Section: Molecular Characteristics Of Sequence and The Encoded Protei...mentioning

confidence: 99%

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Sun

Xie

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Furthermore, PL pro of SARS-CoV has de-ubiquitinating and interferon antagonism effects and subsequently prevents activation of interferon-regulatory factor 3 and inhibits the nuclear factor-j-light-chain-enhancer of activated B cells pathway [ 104 ]. Therefore, the inhibition of these two proteases is expected to suppress replication and translation of the SARS-CoV-2 and was suggested as a promising antiviral drug target [ 105 , 106 ]. For instance, using a combination of lopinavir and ritonavir can decrease the virus load in COVID-19 patients [ 107 ].…”

Section: Pharmaceutical Targets Of Sars-cov-2mentioning

confidence: 99%

Oral antiviral treatments for COVID-19: opportunities and challenges

Rahmah

Arero²,

Jibril³

et al. 2022

Pharmacol. Rep

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The use of antiviral COVID-19 medications can successfully inhibit SARS-CoV-2 replication and prevent disease progression to a more severe form. However, the timing of antiviral treatment plays a crucial role in this regard. Oral antiviral drugs provide an opportunity to manage SARS-CoV-2 infection without a need for hospital admission, easing the general burden that COVID-19 can have on the healthcare system. This review paper (i) presents the potential pharmaceutical antiviral targets, including various host-based targets and viral-based targets, (ii) characterizes the first-generation anti-SARS-CoV-2 oral drugs (nirmatrelvir/ritonavir and molnupiravir), (iii) summarizes the clinical progress of other oral antivirals for use in COVID-19, (iv) discusses ethical issues in such clinical trials and (v) presents challenges associated with the use of oral antivirals in clinical practice. Oral COVID-19 antivirals represent a part of the strategy to adapt to long-term co-existence with SARS-CoV-2 in a manner that prevents healthcare from being overwhelmed. It is pivotal to ensure equal and fair global access to the currently available oral antivirals and those authorized in the future.

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“…Docking studies on naphthalene-based structures or their isosteres have shown that they can create a π-π interaction with the PLpro structure. Cysteine is an important amino acid in the PLpro structure because it attacks the positive charge centers in drugs, allowing cysteine to participate in nucleophilic reactions, addition, and the formation of a covalent bond between the drug and the receptor [ 152 ].…”

Section: Discussionmentioning

confidence: 99%