Evidence map›Paper›PMID 35313575›Full record

ArticlebioRxiv : the preprint server for biology2022

Targeting an evolutionarily conserved "E-L-L" motif in the spike protein to develop a small molecule fusion inhibitor against SARS-CoV-2.

Indrani Das Jana, Prabuddha Bhattacharya, Karthick Mayilsamy, Saptarshi Banerjee, Gourab Bhattacharje, Sayan Das, Seemanti Aditya, Anandita Ghosh, Andrew R McGill, Syamanthak Srikrishnan and 8 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2022. 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, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

Indrani Das JanaSchool of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, India.
Prabuddha BhattacharyaDepartment of Chemistry, Mrinalini Datta Mahavidyapith, Kolkata, India.
Karthick MayilsamyDepartment of Molecular Medicine, University of South Florida, Tampa, USA.
Saptarshi BanerjeeSchool of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, India.
Gourab BhattacharjeDepartment of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.
Sayan DasSchool of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, India.
Seemanti AdityaSchool of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, India.
Anandita GhoshDepartment of Molecular Medicine, University of South Florida, Tampa, USA.
Andrew R McGillDepartment of Molecular Medicine, University of South Florida, Tampa, USA.
Syamanthak SrikrishnanDepartment of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.
Amit Kumar DasDepartment of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.
Amit BasakDivision of Chemical Science, Indian Institute of Science Education and Research Kolkata, Mohanpur, India.
Shyam S MohapatraDepartment of Internal Medicine, University of South Florida, Tampa, USA.
Bala ChandranDepartment of Molecular Medicine, University of South Florida, Tampa, USA.
Devesh BhimsariaBioinformaticals, Jaipur, India.
Subhra MohapatraDepartment of Molecular Medicine, University of South Florida, Tampa, USA.
Arunava RoyDepartment of Molecular Medicine, University of South Florida, Tampa, USA.
Arindam MondalSchool of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, India.
Indian Institute of Technology Kharagpur · INUniversity of South Florida · USIndian Institute of Science Education and Research Kolkata · IN

Funding

KSHV interactions with host nuclear innate response componentsR01CA180758 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI CHANDRAN, BALA · 2014 to 2023
$3.4M
BLRD VA I01 BX005490BLRD VA IK6 BX003778BLRD VA IK6 BX004212NCI NIH HHS R01 CA180758
6 · The paper itself

Abstract

As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key towards sustenance. Here, we identify an evolutionary conserved E-L-L motif present within the HR2 domain of all human and non-human coronavirus spike (S) proteins that play a crucial role in stabilizing the post-fusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this E-L-L motif resulting in effective inhibition of SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy towards blocking S protein-mediated viral entry, mutations within the E-L-L motif rendered the protein completely resistant to the drug, establishing its specificity towards this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective towards all major variants of concerns of SARS-CoV-2 including beta, kappa, delta, and omicron. Together, we show that this conserved essential E-L-L motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.

Identifiers

PMID35313575
PMCPMC8936095
OpenAlexW4221006011

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.