Evidence map›Paper›PMID 40964377›Full record

ArticlebioRxiv : the preprint server for biology2025

Structure-based discovery of inhibitors of Mac1 domain of nonstructural protein-3 of SARS-CoV-2 by machine learning-augmented screening of chemical space.

Fuqiang Ban, Rahul Ravichandran, Galen J Correy, Oleksandra Herasymenko, Madhushika Silva, Suzanne Ackloo, Albina Bolotokova, Irene Chau, Elisa Gibson, Rachel Harding and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Fuqiang BanThe Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Rahul RavichandranDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada.
Galen J CorreyDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States.
Oleksandra HerasymenkoStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Madhushika SilvaStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Suzanne AcklooStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Albina BolotokovaStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Irene ChauStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Elisa GibsonStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Rachel HardingStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Ashley HutchinsonStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Peter LoppnauStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
James S FraserDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States.
Matthieu SchapiraStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Artem CherkasovThe Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Francesco GentileDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada.ORCID 0000-0001-8299-1976

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI James Solomon Fraser · 2022 to 2026
$103.4M
Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, WILLSON, TIMOTHY M · 2022 to 2022
$65.5M
Equipment for Discovering and Manipulating Macromolecular Conformational EnsemblesR35GM145238 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI James Solomon Fraser · 2022 to 2026
$3.1M
NIAID NIH HHS U19 AI171110NIAID NIH HHS U19 AI171292NIGMS NIH HHS R35 GM145238
6 · The paper itself

Abstract

Significant efforts have been recently dedicated to the discovery of small molecule inhibitors against the Macrodomain 1 (Mac1) of nonstructural protein 3 (NSP3) as potential antivirals for SARS-CoV-2. Thus, Mac1 has also been selected as the target for the Critical Assessment of Hit-finding Experiments (CACHE) challenge #3. As contestants in that challenge, we developed a computational strategy that ranked on the top among all 23 participants in the competition and resulted in the discovery of a novel chemical series of non-charged Mac1 inhibitors. Those have been identified through the combination of machine learning-accelerated virtual screening of Enamine REAL Diversity Subset of approximately 25 million compounds and consequent hit expansion into the entire Enamine REAL Space library. In particular, the initially identified hit compound CACHE3-HI_1706_56 (K

Indexed as

CACHE challengeMac1machine learningSARS-CoV-2Virtual screening

Identifiers

PMID40964377
PMCPMC12440007

What Socratic holds

Textmetadata
LicenceCC0
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 Socratic graph.