Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase.
Virol Sin
; 38(3): 470-479, 2023 Jun.
Article
in English
| MEDLINE | ID: covidwho-2320882
ABSTRACT
COVID-19 has become a global public health crisis since its outbreak in China in December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 are involved in the viral replication, and might be prospective targets for anti-coronavirus drug development. Here, we investigated the antiviral activity of oridonin, a natural small-molecule compound, against SARS-CoV-2 infection in vitro. The time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry stage. Mechanistically, the inhibition of viral replication by oridonin depends on the oxidation activity of α, ß-unsaturated carbonyl. Further experiments showed that oridonin not only effectively inhibited SARS-CoV-2 Mpro activity, but also had some inhibitory effects on PLpro-mediated deubiquitinating and viral polymerase-catalyzed RNA elongation activities at high concentrations. In particular, oridonin could inhibit the bat SARS-like CoV and the newly emerged SARS-CoV-2 omicron variants (BA.1 and BA.2), which highlights its potential as a pan-coronavirus antiviral agent. Overall, our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Type of study:
Observational study
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Virol Sin
Journal subject:
Virology
Year:
2023
Document Type:
Article
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