Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase.
Biochem J
; 478(13): 2405-2423, 2021 07 16.
Article
in English
| MEDLINE | ID: covidwho-1292181
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here, we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterized pharmaceuticals for nsp13 inhibitors using a fluorescence resonance energy transfer-based high-throughput screening approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Viral Nonstructural Proteins
/
RNA Helicases
/
Drug Evaluation, Preclinical
/
Small Molecule Libraries
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Traditional medicine
/
Vaccines
/
Variants
Limits:
Animals
Language:
English
Journal:
Biochem J
Year:
2021
Document Type:
Article
Affiliation country:
Bcj20210201
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