Identification of potent small molecule inhibitors of SARS-CoV-2 entry.
SLAS Discov
; 27(1): 8-19, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1641663
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 severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Cysteine Proteinase Inhibitors
/
Dipeptides
/
Virus Attachment
/
Virus Internalization
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Traditional medicine
/
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
SLAS Discov
Year:
2022
Document Type:
Article
Affiliation country:
J.slasd.2021.10.012
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