Evidence map›Paper›PMID 33140046›Full record

ArticlebioRxiv : the preprint server for biology2020

A cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells.

Drake M Mellott, Chien-Te Tseng, Aleksandra Drelich, Pavla Fajtová, Bala C Chenna, Demetrios H Kostomiris, Jason Hsu, Jiyun Zhu, Zane W Taylor, Vivian Tat and 19 more

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

Article in bioRxiv : the preprint server for biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 17 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 5 institutions in 2 countries.

Drake M MellottDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Chien-Te TsengDepartment of Microbiology and Immunology, University of Texas, Medical Branch, 3000 University Boulevard, Galveston, Texas, 77755-1001.
Aleksandra DrelichDepartment of Microbiology and Immunology, University of Texas, Medical Branch, 3000 University Boulevard, Galveston, Texas, 77755-1001.
Pavla FajtováSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Bala C ChennaDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Demetrios H KostomirisDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Jason HsuDepartment of Microbiology and Immunology, University of Texas, Medical Branch, 3000 University Boulevard, Galveston, Texas, 77755-1001.
Jiyun ZhuDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Zane W TaylorDepartment of Chemistry, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Vivian TatDepartment of Microbiology and Immunology, University of Texas, Medical Branch, 3000 University Boulevard, Galveston, Texas, 77755-1001.
Ardala KatzfussDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Linfeng LiDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Miriam A GiardiniSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Danielle SkinnerSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Ken HirataSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Sungjun BeckSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Aaron F CarlinDepartment of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.
Alex E ClarkSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Laura BerettaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Daniel ManevalSelva Therapeutics, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322.
Felix FruehSelva Therapeutics, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322.
Brett L HurstInstitute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322.
Hong WangInstitute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322.
Klaudia I KocurekDepartment of Chemistry, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Frank M RaushelDepartment of Chemistry, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
Anthony J O'DonoghueSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Jair Lage de Siqueira-NetoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Thomas D MeekDepartment of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77843.
James H McKerrowSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
University of California San Diego · USTexas A&M University · USThe University of Texas Medical Branch at Galveston · USUtah State University · USBattelle · US

Funding

World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)R24AI120942 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI WEAVER, SCOTT C · 2016 to 2024
$8.5M
T CELL MEMORY TO VIRUSESR01AI030048 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AHMED, RAFI · 1990 to 2022
$5.2M
T CELL MEMORY TO VIRUSESR37AI030048 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI · 2001 to 2010
$3.9M
NIAID NIH HHS N01 AI030048NIAID NIH HHS R24 AI120942
6 · The paper itself

Abstract

K777 is a di-peptide analog that contains an electrophilic vinyl-sulfone moiety and is a potent, covalent inactivator of cathepsins. Vero E6, HeLa/ACE2, Caco-2, A549/ACE2, and Calu-3, cells were exposed to SARS-CoV-2, and then treated with K777. K777 reduced viral infectivity with EC50 values of inhibition of viral infection of: 74 nM for Vero E6, <80 nM for A549/ACE2, and 4 nM for HeLa/ACE2 cells. In contrast, Calu-3 and Caco-2 cells had EC50 values in the low micromolar range. No toxicity of K777 was observed for any of the host cells at 10-100 μM inhibitor. K777 did not inhibit activity of the papain-like cysteine protease and 3CL cysteine protease, encoded by SARS-CoV-2 at concentrations of ≤ 100 μM. These results suggested that K777 exerts its potent anti-viral activity by inactivation of mammalian cysteine proteases which are essential to viral infectivity. Using a propargyl derivative of K777 as an activity-based probe, K777 selectively targeted cathepsin B and cathepsin L in Vero E6 cells. However only cathepsin L cleaved the SARS-CoV-2 spike protein and K777 blocked this proteolysis. The site of spike protein cleavage by cathepsin L was in the S1 domain of SARS-CoV-2 , differing from the cleavage site observed in the SARS CoV-1 spike protein. These data support the hypothesis that the antiviral activity of K777 is mediated through inhibition of the activity of host cathepsin L and subsequent loss of viral spike protein processing.

Identifiers

PMID33140046
PMCPMC7605553
OpenAlexW3094218704

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.