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Last updated: 2022 Mar 11
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Original Article
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X-ray diffraction structures of Nirmatrelvir (PF-07321332) with Mpro of variants of concern having mutations [Alpha, Beta, Gamma(K90R), Lambda (G15S) and Omicron (P132H)], show that the binding of nirmatrelvir is not disturbed by the mutations. The ligand has the same protein interactions as observed in the wild type MPro from the variant USA-WA1/2020. 1. The crystal structures also show that the mutations do not give rise to any signification changes of the protein around the binding pocket or the site of the mutation.
2. The catalytic efficiencies (kcat/Km) of the K90R (28255 S-1M-1), G15S (16483 S-1M-1), and P132H (22692 S-1M-1) are similar to wildtype Mpro (39830 S-1M-1).
3. Nirmatrelvir potently inhibited wildtype (mean Ki of 0.93 nM) and the mutated enzymes containing the K90R (Ki 1.05nM), G15S (Ki 4.07 nM) and P132H (Ki 0.64 nM)Mpro.
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PMID
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Title Structural basis for Nirmatrelvir in vitro efficacy against SARS-CoV-2 variants
Impact factor
N/A
Date of Entry 2022 Mar 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure. Here, rabbit 80S ribosome colliding in another ribosome stalled by the SARS-CoV-2 pseudoknot is structurally characterized. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
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 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure. By cryo-electron microscopy the structure of rabbit 80S ribosome in complex with eRF1 and ABCE1, stalled at the STOP codon in the mutated SARS-CoV-2 slippery site is studied. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure was studied by cryo-electron microscopy. The rabbit 80S ribosome is stalled close to the mutated SARS-CoV-2 slippery site by a pseudoknot. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

The pseudoknot at the entry to the mRNA channel is a key structural characteristic for translation of the SARS-CoV-2 RNA genome. It specifically interacts with ribosomal proteins (Rabbit 80S ribosome) and 18S rRNA and causes ribosomal pausing prior to -1 frameshifting and the translating ribosome structure was studied by cryo-electron microscopy to a high resolution. Interfering with the frameshifting process at the level of nascent chain interactions with the ribosomal tunnel at the level of RNA folding leads to the formation of the frameshift stimulatory pseudoknot, representing a viable strategy in the search for new drugs against SARS-CoV-2.
✍
 		34029205
(Science)
PMID
34029205
Date of Publishing: 2021 Jun 18
Title Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
Author(s) nameBhatt PR, Scaiola A et al.
Journal Science
Impact factor
20.57
Citation count: 51
Date of Entry 2021 Aug 11

Structure of the 28-kDa (88nt) frameshift stimulation element (FSE) from the SARS-CoV-2 RNA Genome The model for SARS-CoV-2 frameshifting and binding sites may be targeted by next-generation ASOs and small molecules.
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 		Pre-print (bioRXiv)
Title Cryo-electron Microscopy and Exploratory Antisense Targeting of the 28-kDa Frameshift Stimulation Element from the SARS-CoV-2 RNA Genome.
Author(s) name -
Impact factor
N/A
Date of Entry 2021 Jun 14