Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Open access
Collections
- CDTS - Artigos de Periódicos [475]
- IOC - Artigos de Periódicos [12828]
Metadata
Show full item record
PRECLINICAL DEVELOPMENT OF KINETIN AS A SAFE ERROR-PRONE SARS-COV-2 ANTIVIRAL ABLE TO ATTENUATE VIRUS-INDUCED INFLAMMATION
Author
Affilliation
Abstract in Portuguese
O artigo trata do desenvolvimento de um antiviral de uso oral contra a Covid-19. A substância, batizada de MB-905, foi purificada a partir da cinetina e demonstrou-se eficaz para inibir a replicação do Sars-CoV-2 em linhagens de células humanas hepáticas e pulmonares, além de auxiliar a frear o processo inflamatório desencadeado pelo vírus.
Abstract
Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-
19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of
SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and
induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-
905 shows good oral absorption, its metabolites are stable, achieving longlasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice
and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.
Share