ALG-097111, a potent and selective SARS-CoV-2 3-chymotrypsin-like cysteine protease inhibitor exhibits in vivo efficacy in a Syrian Hamster model
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
There is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight the current COVID-19 pandemic. The SARS-CoV-2 main protease (3CLpro) represents a promising target for antiviral therapy. The lack of selectivity for some of the reported 3CLpro inhibitors, specifically versus cathepsin L, raises potential safety and efficacy concerns. ALG-097111 potently inhibited SARS-CoV-2 3CLpro (IC 50 = 7 nM) without affecting the activity of human cathepsin L (IC 50 > 10 μM). When ALG-097111 was dosed in hamsters challenged with SARS-CoV-2, a robust and significant 3.5 log 10 (RNA copies/mg) reduction of the viral RNA copies and 3.7 log 10 (TCID50/mg) reduction in the infectious virus titers in the lungs was observed. These results provide the first in vivo validation for the SARS-CoV-2 3CLpro as a promising therapeutic target for selective small molecule inhibitors.
Article activity feed
-
SciScore for 10.1101/2021.02.14.431129: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Human β-coronavirus OC43 assay: The human beta-coronavirus OC43 assay in HeLa cells was performed as previously described. HeLasuggested: CLS Cat# 300194/p772_HeLa, RRID:CVCL_0030)[13] Human α-Coronavirus 229E assay: The human alpha-coronavirus 229E was purchased from Virapur (San Diego, CA) and propagated using MRC-5 human lung fibroblast cells (ATCC). MRC-5suggested: ICLC Cat# HL95001, RRID:CVCL_0440)Huh7 cells (JCRB cell Bank) were … SciScore for 10.1101/2021.02.14.431129: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Human β-coronavirus OC43 assay: The human beta-coronavirus OC43 assay in HeLa cells was performed as previously described. HeLasuggested: CLS Cat# 300194/p772_HeLa, RRID:CVCL_0030)[13] Human α-Coronavirus 229E assay: The human alpha-coronavirus 229E was purchased from Virapur (San Diego, CA) and propagated using MRC-5 human lung fibroblast cells (ATCC). MRC-5suggested: ICLC Cat# HL95001, RRID:CVCL_0440)Huh7 cells (JCRB cell Bank) were cultured using DMEM media, supplemented with 10 % fetal bovine serum (FBS), 1% (v/v Huh7suggested: NoneSARS-CoV-2 nanoluciferase assay in human ACE-2 expressing A549 cells: The SARS-CoV-2 nanoluciferase assay using A549 cells expressing the human ACE-2 receptor was performed in the laboratory of Pei-Yong Shi at the University of Texas, Medical Branch [14] on behalf of Aligos Therapeutics, Inc. A549suggested: NoneExperimental Models: Organisms/Strains Sentences Resources SARS-CoV-2 3CLpro and human cathepsin L biochemical assays: The SARS-CoV-2 3CLpro and human cathepsin L assays were performed as previously described [12]. SARS-CoV-2 3CLprosuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
-
