Evidence map›Paper›PMID 35874165›Full record

ArticleChem2022

Accelerating PERx reaction enables covalent nanobodies for potent neutralization of SARS-CoV-2 and variants.

Bingchen Yu, Shanshan Li, Takako Tabata, Nanxi Wang, Li Cao, G Renuka Kumar, Wei Sun, Jun Liu, Melanie Ott, Lei Wang

Open access · bronzeAbstract read
In one paragraph

Article in Chem, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 56 citations in OpenAlex.

  1. Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026
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  6. Editor's pick: Enlaza Therapeutics.Nature biotechnology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Bingchen YuDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Shanshan LiDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Takako TabataGladstone Institutes, San Francisco, CA 94158, USA.
Nanxi WangDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Li CaoDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
G Renuka KumarGladstone Institutes, San Francisco, CA 94158, USA.
Wei SunDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Jun LiuDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Melanie OttGladstone Institutes, San Francisco, CA 94158, USA.
Lei WangDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
University of California, San Francisco · USGladstone Institutes · US

Funding

Role of Factor Acetylation in the Regulation of HIV TranscriptionR37AI083139 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Melanie Maria Ott · 2019 to 2026
$5.5M
Covalent Protein Binders for Cancer Research and TherapyR01CA258300 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WANG, LEI · 2021 to 2025
$2.0M
NCI NIH HHS R01 CA258300NIAID NIH HHS R37 AI083139
6 · The paper itself

Abstract

The long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity, yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here, we have developed covalent nanobodies capable of binding with SARS-CoV-2 irreversibly via a proximity-enabled reactive therapeutic (PERx) mechanism. A latent bioreactive amino acid (FFY) was designed and genetically encoded into nanobodies to accelerate the PERx reaction rate. Compared with the noncovalent wild-type nanobody, the FFY-incorporated covalent nanobodies neutralized both wild-type SARS-CoV-2 and its Alpha, Delta, Epsilon, Lambda, and Omicron variants with drastically higher potency. This PERx-enabled covalent-nanobody strategy and the related insights into increased potency can be valuable to developing effective therapeutics for various viral infections.

Indexed as

covalent protein drugCOVID-19genetic code expansioninfectious diseaselatent bioreactive unnatural amino acidnanobodyproximity-enabled reactivitySARS-CoV-2spike-ACE2 interactionsulfur fluoride exchange (SuFEx) click chemistry

Identifiers

PMID35874165
PMCPMC9288967
OpenAlexW4285806329

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.