Conserved coronavirus proteins as targets of broad-spectrum antivirals.
Antiviral Res
; 204: 105360, 2022 08.
Article
in English
| MEDLINE | ID: covidwho-1881679
ABSTRACT
Coronaviruses are a class of single-stranded, positive-sense RNA viruses that have caused three major outbreaks over the past two decades Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All outbreaks have been associated with significant morbidity and mortality. In this study, we have identified and explored conserved binding sites in the key coronavirus proteins for the development of broad-spectrum direct acting anti-coronaviral compounds and validated the significance of this conservation for drug discovery with existing experimental data. We have identified four coronaviral proteins with highly conserved binding site sequence and 3D structure similarity PLpro, Mpro, nsp10-nsp16 complex(methyltransferase), and nsp15 endoribonuclease. We have compiled all available experimental data for known antiviral medications inhibiting these targets and identified compounds active against multiple coronaviruses. The identified compounds representing potential broad-spectrum antivirals include GC376, which is active against six viral Mpro (out of six tested, as described in research literature); mycophenolic acid, which is active against four viral PLpro (out of four); and emetine, which is active against four viral RdRp (out of four). The approach described in this study for coronaviruses, which combines the assessment of sequence and structure conservation across a viral family with the analysis of accessible chemical structure - antiviral activity data, can be explored for the development of broad-spectrum drugs for multiple viral families.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Middle East Respiratory Syndrome Coronavirus
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Antiviral Res
Year:
2022
Document Type:
Article
Affiliation country:
J.antiviral.2022.105360
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